Ferroptosis is a new type of programmed cell death caused by the accumulation of iron-dependent lipid peroxides,and it plays a role in the occurrence and progression of diverse diseases.Diabetic cardiomyopathy(DCM),a ...Ferroptosis is a new type of programmed cell death caused by the accumulation of iron-dependent lipid peroxides,and it plays a role in the occurrence and progression of diverse diseases.Diabetic cardiomyopathy(DCM),a serious cardiovascular complication in patients with diabetes,eventually progresses to refractory heart failure(HF),which increases the risk of hospitalization for HF and cardiovascular death in patients with diabetes.Despite glycemic control,effective strategies to prevent DCM onset are currently lacking.Accumulating evidence suggests that ferroptosis is involved in oxidative stress,inflammation,and abnormal autophagy in diabetic myocardium,which plays an important role in myocardial apoptosis,hypertrophy,and cardiac fibrosis.The inhibition of ferroptosis can relieve DCM.Presently,ferroptosis inhibitors have been broadly suggested for the treatment of iron overload-related cardiomyopathy.This article reviewed relevant studies to offer a new therapeutic target for DCM.展开更多
BACKGROUND Recent studies have shown that liraglutide,a glucagon-like peptide-1 receptor agonist,has unexpected cardioprotective effects.However,the distinctive effects of liraglutide on diabetic cardiomyopathy(DCM),p...BACKGROUND Recent studies have shown that liraglutide,a glucagon-like peptide-1 receptor agonist,has unexpected cardioprotective effects.However,the distinctive effects of liraglutide on diabetic cardiomyopathy(DCM),particularly its effect on mitophagy,have not been fully elucidated.AIM To investigate the effects of liraglutide on cardiac damage and mitophagy in DCM rats.METHODS A high-fat diet and streptozotocin were used to induce DCM in rats.After 12 weeks of liraglutide treatment,rats underwent assessments of cardiac function,serum biochemical parameters,histological changes,apoptosis index,and protein levels.Furthermore,neonatal rat cardiomyocytes(NRCMs)were exposed to 25 mmol/L glucose plus 250μmol/L palmitate(high glucose+palmitic acid),with or without 200 nmol/L liraglutide,to investigate the effects of liraglutide on cardiomyocyte injury and the underlying mechanisms.RESULTS Liraglutide improved myocardial function and ameliorated cardiac damage in DCM rats,as indicated by reduced myocardial apoptosis,hypertrophy,and interstitial fibrosis(P<0.05).In NRCMs,Liraglutide alleviated mitochondrial morphological and functional damage as well as oxidative stress,improved mitophagic defects,and reduced cell apoptosis(P<0.05).Mechanistically,liraglutide alleviated NRCMs damage by enhancing mitophagy mediated by the adenosine monophosphate-activated protein kinase(AMPK)-Parkin signaling pathway,which was evidenced by the reversal of its effects upon compound C treatment.CONCLUSION Liraglutide exerted cardioprotective effects in DCM rats by inhibiting cardiomyocyte apoptosis and promoting mitophagy mediated by the AMPK-Parkin signaling pathway.展开更多
Diabetic cardiomyopathy(DCM)is a major cause of heart failure in diabetic patients.It progresses asymptomatically prior to the onset of severe cardiac symptoms[1];therefore,elucidating the underlying mechanisms of DCM...Diabetic cardiomyopathy(DCM)is a major cause of heart failure in diabetic patients.It progresses asymptomatically prior to the onset of severe cardiac symptoms[1];therefore,elucidating the underlying mechanisms of DCM is critical to providing early treatment options.This commentary elaborates on the findings of Jiang et al.[2],who investigated the role of adipokine hormone,Adipsin,as a cardioprotective factor in DCM.We provide an exposition and alternative treatment considerations,like Fisetin,and discuss the potential of investigating other cellular targets implicated in cardiac dysfunction,like the interleukin-1 receptor-associated kinaselike 2(Irak2)protein[3]and protein kinase R[4].展开更多
BACKGROUND Erianin is a natural bibenzyl compound extracted from Dendrobium chrysotoxum and is known for its anti-inflammatory and antioxidant properties.AIM To explore the possible therapeutic mechanisms of erianin a...BACKGROUND Erianin is a natural bibenzyl compound extracted from Dendrobium chrysotoxum and is known for its anti-inflammatory and antioxidant properties.AIM To explore the possible therapeutic mechanisms of erianin and determine if it can reduce cardiac damage in mice with type 2 diabetes.METHODS High-fat diet and intraperitoneal injections of streptozotocin were used to induce type 2 diabetes mellitus in C57BL/6 mice.Mice were divided into different groups including control,model,and treatment with various doses of erianin(10,20,and 40 mg/kg)as well as ML-385+erianin group.RESULTS Erianin reduced oxidative stress and inflammation and alleviated diabetic cardiomyopathy through the activation of the adenosine monophosphate-acti-vated protein kinase(AMPK)-nuclear factor erythroid 2-related factor 2(Nrf2)-heme oxygenase-1(HO-1)pathway.Treatments with erianin-M and erianin-H promoted weight stabilization and normalized fasting glucose levels relative to diabetic controls.Echocardiographic assessment demonstrated that erianin dose-dependently enhanced left ventricular systolic function(left ventricular ejection fraction,left ventricular fractional shortening)and mitigated ventricular remodeling(left ventricular internal diameter at end-diastole,left ventricular internal diameter at end-systole;P<0.05 vs model group).No significant differences were observed between the ML-385+erianin and placebo-treated groups.Histopathological examination through hematoxylin-eosin staining indicated that erianin ameliorated myocardial fiber fragmentation,structural disorganization,inflammatory cell infiltration,and cytolytic damage.Furthermore,it significantly reduced the serum levels of cardiac troponin I,creatine kinase,and its MB isoenzyme.However,the ML-385+erianin co-treatment failed to alleviate myocardial injury.Metabolic profiling revealed erianin-mediated improvements in glycemic regulation(glycated hemoglobin:P<0.001),plasma insulin homeostasis,and lipid metabolism(total cholesterol,triglycerides,low-density lipo-protein cholesterol reduction,and high-density lipoprotein cholesterol restoration;P<0.05 vs model group).Pro-inflammatory cytokines including tumor necrosis factor-α,interleukin(IL)-1β,and IL-6 were markedly suppressed in the erianin-M and erianin-H groups compared with the model group,whereas no significant differences were detected between the model and ML-385+erianin groups.Oxidative stress parameters showed decreased malondialdehyde levels accompanied by elevated superoxide dismutase and catalase activities in erianin-treated groups,with the most pronounced effects in the erianin-H group(P<0.05).Western blot analysis confirmed the significant upregulation of proteins associated with the AMPK/Nrf2/HO-1 pathway in erianin-M and erianin-H groups.These protective effects were abolished in the ML-385+erianin co-treatment group,which showed no statistical differences from the model group.CONCLUSION Erianin can effectively alleviate myocardial injury in type 2 diabetic mice by activating the AMPK-Nrf2-HO-1 pathway.展开更多
BACKGROUND Diabetic cardiomyopathy(DCM)is the leading cause of cardiovascular diseaserelated mortality.Farrerol(FA)possesses anti-inflammatory and antioxidant properties.However,its role in regulating endothelial ferr...BACKGROUND Diabetic cardiomyopathy(DCM)is the leading cause of cardiovascular diseaserelated mortality.Farrerol(FA)possesses anti-inflammatory and antioxidant properties.However,its role in regulating endothelial ferroptosis in DCM remains unknown.AIM To investigate the beneficial effects of FA on cardiac microvascular dysfunction in DCM from the perspective of ferroptosis in endothelial cells(ECs).METHODS The mice were fed a high-fat diet and injected with streptozotocin to induce DCM.DCM mice were orally administered FA(10 and 40 mg/kg/day)and a tail vein injection of the miR-29b-3p mimic or inhibitor for 24 weeks.Cardiac function and myocardial fibrosis were also analyzed.Cardiac microvascular function was assessed using immunofluorescence and transmission electron microscopy.Ferroptosis was analyzed using RNA sequencing,immunofluorescence,and western blotting.RESULTS FA administration improved cardiac function,alleviated myocardial fibrosis,strengthened endothelial barrier function,suppressed endothelial inflammation,and preserved the microvascular structure in DCM mice.This improvement was associated with the inhibition of endothelial ferroptosis and downregulation of miR-29b-3p in ECs.Similar efficacy was observed after tail vein injection of the miR-29b-3p inhibitor.Inhibition of miR-29b-3p in vivo showed an anti-cardiac fibrotic effect by improving microvascular dysfunction and ferroptosis in ECs,whereas overexpression of miR-29b-3p showed the opposite effects in DCM mice.Luciferase reporter assay revealed that miR-29b-3p binds to SIRT1.In cultured ECs,FA reduced high glucose and free fatty acid(HG/FFA)-induced lipid peroxidation and ferroptosis and inhibited endothelial-mediated inflammation.However,the overexpression of miR-29b-3p partially abolished the protective effects of FA against HG/FFA-induced injury in ECs.This finding suggests that the mechanism of action of FA in improving DCM is related to the downregulation of miR-29b-3p and activation of SIRT1 expression.CONCLUSION Therefore,FA has a potential therapeutic effect on cardiac microvascular dysfunction by suppressing EC ferroptosis through the miR-29b-3p/SIRT1 axis.展开更多
Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary a...Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary ammonium alkaloid isolated from Coptidis Rhizoma,a traditional Chinese medicine,has superior anti-diabetic and heart-protective properties.The purpose of this study is to assess the impact of BBR on DCM.Methods:This study used a systems pharmacology approach to evaluate the related proteins and signalling pathways between BBR and DCM targets,combined with experimental validation using diabetic mouse heart sections.Microstructural and pathological changes were observed using Hematoxylin-eosin,Masson’s trichrome stain and wheat germ agglutinin staining.Immunofluorescence and western blot were used to determine protein expression.Results:The results indicate that BBR and DCM share 21 core relevant targets,with cross-targets predominantly located in mitochondrial,endoplasmic reticulum,and plasma membrane components.BBR exerts its main effects in improving DCM by maintaining mitochondrial integrity,particularly involving the PI3K-AKT-GSK3βand apoptosis signalling pathways.In addition,post-treatment changes in the key targets of BBR,including cysteine aspartate specific protease(Caspase)-3,phosphoinositide 3-kinase(PI3K)and mitochondria-related proteins,are suggestive of its efficacy.Conclusion:BBR crucially improves DCM by maintaining mitochondrial integrity,inhibiting apoptosis,and modulating PI3K-AKT-GSK3βsignaling.Further studies must address animal model limitations and validate clinical efficacy to understand BBR’s mechanisms fully and its potential clinical use.展开更多
Background Diabetic cardiomyopathy(DCM)represents a severe cardiovascular complication of diabetes mellitus,characterized by insidious onset,diagnostic challenges in early stages,and poor prognosis.Current diagnosis o...Background Diabetic cardiomyopathy(DCM)represents a severe cardiovascular complication of diabetes mellitus,characterized by insidious onset,diagnostic challenges in early stages,and poor prognosis.Current diagnosis of DCM primarily relies on imaging techniques,lacking convenient and effective early biomarkers.Method Using a case-control study design,we enrolled 50 DCM patients(DCM group)and 50 diabetes-only patients(control group)diagnosed at our hospital between January 2023 and January 2025.Demographic data were collected from all participants.Serum levels of hemoglobinA1c(HbAlc),interleukin-1β(IL-1β),and superoxide dismutase(SOD)were measured and compared between groups.Logistic regression analysis was performed to identify DCM risk factors,while receiver operating characteristic(ROC)curve analysis evaluated the diagnostic value of individual and combined biomarkers for DCM screening.Results The levels of HbAlc and IL-1βin the DCM group were higher than those in the control group,and the level of SOD was lower than that in the control group(P<0.05).Multivariate Logistic regression analysis showed that HbAlc,IL-1βand SOD were all independent risk factors for DCM.The results of the ROC curve showed that the areas under curve(AUC)of HbA1c,IL-1β,and SOD levels in diagnosing DCM patients were 0.673,0.783,and 0.728,respectively.The AUC predicted by the combination of the three was 0.836,which was higher than that detected by any above single index(P<0.05).Conclusions DCM patients exhibited significantly higher HbAlc and IL-1βlevels but lower SOD activity compared to the controls.Each biomarker demonstrated significant diagnostic value for DCM,and their combination yielded superior diagnostic performance compared to any single marker.展开更多
Objective： To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyo- pathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. Methods： ...Objective： To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyo- pathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. Methods： Sixty Sprague-Dawley （SD） rats were randomly divided into six groups： a normal control group （NC）, an obesity group （OB）, a diabetic cardiomyopathy group （DCM）, a tea polyphenol group （TP）, an obesity tea polyphenol treatment group （OB-TP）, and a diabetic cardiomyopathy tea polyphenol treatment group （DCM-TP）. After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ul- trasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-11, SQSTM1/p62, and Beclin-1 were determined by Western blotting. Results： Com- pared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-11/I and Beclin-1 increased obviously whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups （P〈0.05）. Conclusions： Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.展开更多
Diabetes mellitus(DM) is characterised by hyperglycemia, insulin resistance and metabolic dysregulation leading to diastolic and systolic dysfunction in diabetes. In this review, the pathogenetic and pathomorphologica...Diabetes mellitus(DM) is characterised by hyperglycemia, insulin resistance and metabolic dysregulation leading to diastolic and systolic dysfunction in diabetes. In this review, the pathogenetic and pathomorphological changes leading to diastolic and systolic dysfunction in diabetes are discussed. Changes in metabolic signalling pathways, mediators and effectors contribute to the pathogenesis of cardiac dysfunction in DM called diabetic cardiomyopathy(DC). Echocardiographic studies report on the association between DM and the presence of cardiac hypertrophy and myocardial stiffness that lead to diastolic dysfunction. More recently reported echocardiographic studies with more sensitive techniques, such as strain analysis, also observed systolic dysfunction as an early marker of DC. Depression of systolic and diastolic function is continuum and the line of separation is artificial. To conclude, according to current knowledge, DC is expected to be a common single phenotype that is caused by different pathogenetic and pathomorphological changes leading to diastolic and systolic dysfunction in diabetes.展开更多
Objective:To study the effect of Shengmai San(生脉散Pulse-activating Powder) in protecting myocardium in the rat of the type 2 diabetic cardiomyopathy(DCM) model.Methods:The DCM rat model was established by combinatio...Objective:To study the effect of Shengmai San(生脉散Pulse-activating Powder) in protecting myocardium in the rat of the type 2 diabetic cardiomyopathy(DCM) model.Methods:The DCM rat model was established by combination of insulin resistance induced by a high-fat diet with intraperitoneal injection of high dose streptozotocin(50 mg/kg).And these rat models were randomly divided into three groups:a normal group(n=12,one of them died),a model group(n=15) and a Shengmai San group(treatment group,n=15).The damage of the myocardium was assessed by electrocardiogram at the twelfth week after modeling,and the blood glucose,cholesterol and triglyceride levels were determined;the content of the left cardiac ventricle myocardial collagen was quantified by Masson staining test;the level of myocardial cell apoptosis was detected with TUNEL apoptosis detection kit;the damage extent of the myocardial sub-cellular structures was observed by electron microscopy;the expression levels of cardiac TSP-1(Thrombospondin-1),TGF-β1(Transforming Growth Ffactor-β) and TRB-3(Tribbles homolog 3) proteins were detected by immunohistochemical method;the expression levels of cardiac TSP-1,A-TGF-β1 and L-TGF-β1 proteins were detected by Western blotting;and the expression levels of TSP-1 and TRB-3 mRNAs were detected by real-time quantitative PCR.Results:Compared with the control group,the blood glucose,cholesterol,triglycerides levels in both the model groups and the Shengmai San group were significantly decreased;the myocardial tissue was less damaged and the collagen content was reduced in the Shengmai San group;the myocardial sub-cellular structure was injured to a lesser extent;the expression levels of myocardial TSP-1,TGF-β1,TRB-3,and TSP-1,A-TGF-β1,L-TGF-β1 and chymase were decreased,and the expression levels of TSP-1 mRNA and TRB-3 mRNA were decreased in both the model groups and the Shengmai San group(the latter was better),.Conclusion:Shengmai San can inhibit myocardial fibrosis in the rat of diabetic cardiomyopathy,and significantly delay the formation of diabetic cardiomyopathy in hyperglycemia rats through multiple pathways.展开更多
BACKGROUND Diabetic cardiomyopathy(DCM)increases the risk of hospitalization for heart failure(HF)and mortality in patients with diabetes mellitus.However,no specific therapy to delay the progression of DCM has been i...BACKGROUND Diabetic cardiomyopathy(DCM)increases the risk of hospitalization for heart failure(HF)and mortality in patients with diabetes mellitus.However,no specific therapy to delay the progression of DCM has been identified.Mitochondrial dysfunction,oxidative stress,inflammation,and calcium handling imbalance play a crucial role in the pathological processes of DCM,ultimately leading to cardiomyocyte apoptosis and cardiac dysfunctions.Empagliflozin,a novel glucoselowering agent,has been confirmed to reduce the risk of hospitalization for HF in diabetic patients.Nevertheless,the molecular mechanisms by which this agent provides cardioprotection remain unclear.AIM To investigate the effects of empagliflozin on high glucose(HG)-induced oxidative stress and cardiomyocyte apoptosis and the underlying molecular mechanism.METHODS Twelve-week-old db/db mice and primary cardiomyocytes from neonatal rats stimulated with HG(30 mmol/L)were separately employed as in vivo and in vitro models.Echocardiography was used to evaluate cardiac function.Flow cytometry and TdT-mediated dUTP-biotin nick end labeling staining were used to assess apoptosis in myocardial cells.Mitochondrial function was assessed by cellular ATP levels and changes in mitochondrial membrane potential.Furthermore,intracellular reactive oxygen species production and superoxide dismutase activity were analyzed.Real-time quantitative PCR was used to analyze Bax and Bcl-2 mRNA expression.Western blot analysis was used to measure the phosphorylation of AMP-activated protein kinase(AMPK)and myosin phosphatase target subunit 1(MYPT1),as well as the peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)and active caspase-3 protein levels.RESULTSIn the in vivo experiment, db/db mice developed DCM. However, the treatment of db/db mice with empagliflozin(10 mg/kg/d) for 8 wk substantially enhanced cardiac function and significantly reduced myocardial apoptosis,accompanied by an increase in the phosphorylation of AMPK and PGC-1α protein levels, as well as a decrease inthe phosphorylation of MYPT1 in the heart. In the in vitro experiment, the findings indicate that treatment ofcardiomyocytes with empagliflozin (10 μM) or fasudil (FA) (a ROCK inhibitor, 100 μM) or overexpression of PGC-1α significantly attenuated HG-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis.However, the above effects were partly reversed by the addition of compound C (CC). In cells exposed to HG,empagliflozin treatment increased the protein levels of p-AMPK and PGC-1α protein while decreasing phosphorylatedMYPT1 levels, and these changes were mitigated by the addition of CC. Adding FA and overexpressingPGC-1α in cells exposed to HG substantially increased PGC-1α protein levels. In addition, no sodium-glucosecotransporter (SGLT)2 protein expression was detected in cardiomyocytes.CONCLUSION Empagliflozin partially achieves anti-oxidative stress and anti-apoptotic effects on cardiomyocytes under HGconditions by activating AMPK/PGC-1α and suppressing of the RhoA/ROCK pathway independent of SGLT2.展开更多
Diabetic cardiomyopathy(DCM)is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and hypertension.As DCM is now recognized as a cause of substantial morbid...Diabetic cardiomyopathy(DCM)is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and hypertension.As DCM is now recognized as a cause of substantial morbidity and mortality among patients with diabetes mellitus and clinical diagnosis is still inappropriate,various expert groups struggled to identify a suitable biomarker that will help in the recognition and management of DCM,with little success so far.Hence,we thought it important to address the role of biomarkers that have shown potential in either human or animal studies and which could eventually result in mitigating the poor outcomes of DCM.Among the array of biomarkers we thoroughly analyzed,long noncoding ribonucleic acids,soluble form of suppression of tumorigenicity 2 and galectin-3 seem to be most beneficial for DCM detection,as their plasma/serum levels accurately correlate with the early stages of DCM.The combination of relatively inexpensive and accurate speckle tracking echocardiography with some of the highlighted biomarkers may be a promising screening method for newly diagnosed diabetes mellitus type 2 patients.The purpose of the screening test would be to direct affected patients to more specific confirmation tests.This perspective is in concordance with current guidelines that accentuate the importance of an interdisciplinary team-based approach.展开更多
BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM developme...BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM development through the inflammatory response.Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes.Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.AIM To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.METHODS Streptozotocin was administered to induce diabetes in mice,followed by treatment with 30 mg/kg teneligliptin.RESULTS Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening,ejection fraction,and heart rate;increases in creatine kinase-MB(CK-MB),aspartate transaminase(AST),and lactate dehydrogenase(LDH)levels;and upregulated NADPH oxidase 4 were observed in diabetic mice,all of which were significantly reversed by teneligliptin.Moreover,NLRP3 inflammasome activation and increased release of interleukin-1βin diabetic mice were inhibited by teneligliptin.Primary mouse cardiomyocytes were treated with high glucose(30 mmol/L)with or without teneligliptin(2.5 or 5μM)for 24 h.NLRP3 inflammasome activation.Increases in CKMB,AST,and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin,and AMP(p-adenosine 5‘-monophosphate)-p-AMPK(activated protein kinase)levels were increased.Furthermore,the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.CONCLUSION Overall,teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.展开更多
In this editorial,we commented on the article published in the recent issue of the World Journal of Diabetes.Diabetic cardiomyopathy(DCM)is characterized by myocardial fibrosis,ventricular hypertrophy and diastolic dy...In this editorial,we commented on the article published in the recent issue of the World Journal of Diabetes.Diabetic cardiomyopathy(DCM)is characterized by myocardial fibrosis,ventricular hypertrophy and diastolic dysfunction in diabetic patients,which can cause heart failure and threaten the life of patients.The pathogenesis of DCM has not been fully clarified,and it may involve oxidative stress,inflammatory stimulation,apoptosis,and autophagy.There is lack of effective therapies for DCM in the clinical practice.Statins have been widely used in the clinical practice for years mainly to reduce cholesterol and stabilize arterial plaques,and exhibit definite cardiovascular protective effects.Studies have shown that statins also have anti-inflammatory and antioxidant effects.We were particularly concerned about the recent findings that atorvastatin alleviated myocardial fibrosis in db/db mice by regulating the antioxidant stress and antiinflammatory effects of macrophage polarization on diabetic myocardium,and thereby improving DCM.展开更多
Diabetic cardiomyopathy(DCM)is a metabolic disease and a leading cause of heart failure among people with diabetes.Mass spectrometry imaging(MSI)is a versatile technique capable of combining the molecular specificity ...Diabetic cardiomyopathy(DCM)is a metabolic disease and a leading cause of heart failure among people with diabetes.Mass spectrometry imaging(MSI)is a versatile technique capable of combining the molecular specificity of mass spectrometry(MS)with the spatial information of imaging.In this study,we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity.We optimized the air flow-assisted desorption electrospray ionization(AFADESI)-MSI platform to detect a wide range of metabolites,and then used matrix-assisted laser desorption ionization(MALDI)-MSI for increasing metabolic coverage and improving localization resolution.AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections,respectively,while MALDI-MSI detected 61 metabolites in negative analysis.Our study revealed the heterogenous metabolic profile of the heart in a DCM model,with over 105 region-specific changes in the levels of a wide range of metabolite classes,including carbohydrates,amino acids,nucleotides,and their derivatives,fatty acids,glycerol phospholipids,carnitines,and metal ions.The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model.Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.展开更多
Diabetic complications,chiefly seen in long-term situations,are persistently deleterious to a large extent,requiring multi-factorial risk reduction strategies beyond glycemic control.Diabetic cardiomyopathy is one of ...Diabetic complications,chiefly seen in long-term situations,are persistently deleterious to a large extent,requiring multi-factorial risk reduction strategies beyond glycemic control.Diabetic cardiomyopathy is one of the most common deleterious diabetic complications,being the leading cause of mortality among diabetic patients.The mechanisms of diabetic cardiomyopathy are multi-factorial,involving increased oxidative stress,accumulation of advanced glycation end products(AGEs),activation of various pro-inflammatory and cell death signaling pathways,and changes in the composition of extracellular matrix with enhanced cardiac fibrosis.The novel lipid signaling system,the endocannabinoid system,has been implicated in the pathogenesis of diabetes and its complications through its two main receptors:Cannabinoid receptor type 1 and cannabinoid receptor type 2,alongside other components.However,the role of the endocannabinoid system in diabetic cardiomyopathy has not been fully investigated.This review aims to elucidate the possible mechanisms through which cannabinoids and the endocannabinoid system could interact with the pathogenesis and the development of diabetic cardiomyopathy.These mechanisms include oxidative/nitrative stress,inflammation,accumulation of AGEs,cardiac remodeling,and autophagy.A better understanding of the role of cannabinoids and the endocannabinoid system in diabetic cardiomyopathy may provide novel strategies to manipulate such a serious diabetic complication.展开更多
This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used fo...This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.展开更多
Diabetic cardiomyopathy(DbCM)is a common but underrecognized complication of patients with diabetes mellitus(DM).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and ...Diabetic cardiomyopathy(DbCM)is a common but underrecognized complication of patients with diabetes mellitus(DM).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and cardiac autonomic neuropathy are mostly known with reasonable therapeutic options,the mechanisms and management options for DbCM are still not fully understood.In its early stages,DbCM presents with diastolic dysfunction followed by heart failure(HF)with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately managed.Apart from prompt control of DM with lifestyle changes and antidiabetic medications,disease-modifying therapy for DbCM includes prompt control of hypertension and dyslipidemia inherent to patients with DM as in other forms of heart diseases and the use of treatments with proven efficacy in HF.A basic study by Zhang et al,in a recent issue of the World Journal of Diabetes elaborates the potential pathophysiological alterations and the therapeutic role of teneligliptin in diabetic mouse models with DbCM.Although this preliminary basic study might help to improve our understanding of DbCM and offer a potential new management option for patients with the disease,the positive results from such animal models might not always translate to clinical practice as the pathobiology of DbCM in humans could be different.However,such experimental studies can encourage more scientific efforts to find a better solution to treat patients with this enigmatic disease.展开更多
Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively investigated.However,mo...Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively investigated.However,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and pyroptosis.The direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific inhibitors.We thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific conditions.This editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent models.Only clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.展开更多
Background:Diabetic cardiomyopathy is a multifaceted complication of diabetes that lacks effective treatments.Berberine(BBR),a bioactive compound from Rhizoma coptidis,has potential therapeutic implications,but its pr...Background:Diabetic cardiomyopathy is a multifaceted complication of diabetes that lacks effective treatments.Berberine(BBR),a bioactive compound from Rhizoma coptidis,has potential therapeutic implications,but its precise role in diabetic cardiomyopathy remains to be defined.Methods:In this study,a diabetic cardiomyopathy model was established by administration of a high-fat diet and streptozotocin injection to C57BL/6J mice.Concurrently,the mice received BBR treatment daily for a duration of 8 weeks.After the treatment period,myocardial injury,cardiac function,and the levels of oxidative stress and apoptosis were assessed.Results:BBR significantly ameliorated cardiac dysfunction and histopathological damage caused by diabetic cardio-myopathy.This treatment also elevated serum superoxide dismutase levels while decreasing malondialdehyde levels.The anti-apoptotic activity of BBR was evidenced by a decrease in TUNEL-positive cells and the percentage of apop-totic cells,as determined by flow cytometry,in conjunction with diminished levels of BCL2-associated X protein/B cell lymphoma 2(BAX/BCL2)in heart tissues.Mechanistically,BBR was found to ameliorate diabetic cardiomyopa-thy by upregulating the expression of myocardial methionine sulfoxide reductase A(MsrA)and concurrently suppress-ing cardiac CaMKII oxidation.Conclusions:BBR alleviates diabetic cardiomyopathy by inhibiting myocardial apoptosis and oxidative stress through the MsrA and CaMKII signaling pathways.展开更多
文摘Ferroptosis is a new type of programmed cell death caused by the accumulation of iron-dependent lipid peroxides,and it plays a role in the occurrence and progression of diverse diseases.Diabetic cardiomyopathy(DCM),a serious cardiovascular complication in patients with diabetes,eventually progresses to refractory heart failure(HF),which increases the risk of hospitalization for HF and cardiovascular death in patients with diabetes.Despite glycemic control,effective strategies to prevent DCM onset are currently lacking.Accumulating evidence suggests that ferroptosis is involved in oxidative stress,inflammation,and abnormal autophagy in diabetic myocardium,which plays an important role in myocardial apoptosis,hypertrophy,and cardiac fibrosis.The inhibition of ferroptosis can relieve DCM.Presently,ferroptosis inhibitors have been broadly suggested for the treatment of iron overload-related cardiomyopathy.This article reviewed relevant studies to offer a new therapeutic target for DCM.
基金Supported by National Natural Science Foundation of China,No.81370221 and No.82172334PUMC Youth Fund,No.3332018200+1 种基金National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2024ZD0522005CAMS Innovation Fund for Medical Science,No.2016-CXGC05-4 and No.2021-I2M-1-008.
文摘BACKGROUND Recent studies have shown that liraglutide,a glucagon-like peptide-1 receptor agonist,has unexpected cardioprotective effects.However,the distinctive effects of liraglutide on diabetic cardiomyopathy(DCM),particularly its effect on mitophagy,have not been fully elucidated.AIM To investigate the effects of liraglutide on cardiac damage and mitophagy in DCM rats.METHODS A high-fat diet and streptozotocin were used to induce DCM in rats.After 12 weeks of liraglutide treatment,rats underwent assessments of cardiac function,serum biochemical parameters,histological changes,apoptosis index,and protein levels.Furthermore,neonatal rat cardiomyocytes(NRCMs)were exposed to 25 mmol/L glucose plus 250μmol/L palmitate(high glucose+palmitic acid),with or without 200 nmol/L liraglutide,to investigate the effects of liraglutide on cardiomyocyte injury and the underlying mechanisms.RESULTS Liraglutide improved myocardial function and ameliorated cardiac damage in DCM rats,as indicated by reduced myocardial apoptosis,hypertrophy,and interstitial fibrosis(P<0.05).In NRCMs,Liraglutide alleviated mitochondrial morphological and functional damage as well as oxidative stress,improved mitophagic defects,and reduced cell apoptosis(P<0.05).Mechanistically,liraglutide alleviated NRCMs damage by enhancing mitophagy mediated by the adenosine monophosphate-activated protein kinase(AMPK)-Parkin signaling pathway,which was evidenced by the reversal of its effects upon compound C treatment.CONCLUSION Liraglutide exerted cardioprotective effects in DCM rats by inhibiting cardiomyocyte apoptosis and promoting mitophagy mediated by the AMPK-Parkin signaling pathway.
基金supported by the Office of Naval Research Grant(N00014-22-1-2184)。
文摘Diabetic cardiomyopathy(DCM)is a major cause of heart failure in diabetic patients.It progresses asymptomatically prior to the onset of severe cardiac symptoms[1];therefore,elucidating the underlying mechanisms of DCM is critical to providing early treatment options.This commentary elaborates on the findings of Jiang et al.[2],who investigated the role of adipokine hormone,Adipsin,as a cardioprotective factor in DCM.We provide an exposition and alternative treatment considerations,like Fisetin,and discuss the potential of investigating other cellular targets implicated in cardiac dysfunction,like the interleukin-1 receptor-associated kinaselike 2(Irak2)protein[3]and protein kinase R[4].
文摘BACKGROUND Erianin is a natural bibenzyl compound extracted from Dendrobium chrysotoxum and is known for its anti-inflammatory and antioxidant properties.AIM To explore the possible therapeutic mechanisms of erianin and determine if it can reduce cardiac damage in mice with type 2 diabetes.METHODS High-fat diet and intraperitoneal injections of streptozotocin were used to induce type 2 diabetes mellitus in C57BL/6 mice.Mice were divided into different groups including control,model,and treatment with various doses of erianin(10,20,and 40 mg/kg)as well as ML-385+erianin group.RESULTS Erianin reduced oxidative stress and inflammation and alleviated diabetic cardiomyopathy through the activation of the adenosine monophosphate-acti-vated protein kinase(AMPK)-nuclear factor erythroid 2-related factor 2(Nrf2)-heme oxygenase-1(HO-1)pathway.Treatments with erianin-M and erianin-H promoted weight stabilization and normalized fasting glucose levels relative to diabetic controls.Echocardiographic assessment demonstrated that erianin dose-dependently enhanced left ventricular systolic function(left ventricular ejection fraction,left ventricular fractional shortening)and mitigated ventricular remodeling(left ventricular internal diameter at end-diastole,left ventricular internal diameter at end-systole;P<0.05 vs model group).No significant differences were observed between the ML-385+erianin and placebo-treated groups.Histopathological examination through hematoxylin-eosin staining indicated that erianin ameliorated myocardial fiber fragmentation,structural disorganization,inflammatory cell infiltration,and cytolytic damage.Furthermore,it significantly reduced the serum levels of cardiac troponin I,creatine kinase,and its MB isoenzyme.However,the ML-385+erianin co-treatment failed to alleviate myocardial injury.Metabolic profiling revealed erianin-mediated improvements in glycemic regulation(glycated hemoglobin:P<0.001),plasma insulin homeostasis,and lipid metabolism(total cholesterol,triglycerides,low-density lipo-protein cholesterol reduction,and high-density lipoprotein cholesterol restoration;P<0.05 vs model group).Pro-inflammatory cytokines including tumor necrosis factor-α,interleukin(IL)-1β,and IL-6 were markedly suppressed in the erianin-M and erianin-H groups compared with the model group,whereas no significant differences were detected between the model and ML-385+erianin groups.Oxidative stress parameters showed decreased malondialdehyde levels accompanied by elevated superoxide dismutase and catalase activities in erianin-treated groups,with the most pronounced effects in the erianin-H group(P<0.05).Western blot analysis confirmed the significant upregulation of proteins associated with the AMPK/Nrf2/HO-1 pathway in erianin-M and erianin-H groups.These protective effects were abolished in the ML-385+erianin co-treatment group,which showed no statistical differences from the model group.CONCLUSION Erianin can effectively alleviate myocardial injury in type 2 diabetic mice by activating the AMPK-Nrf2-HO-1 pathway.
基金Supported by Medical Health Science and Technology Project of Zhejiang Provincial,No.2025KY1721 and No.2022KY1292Science and Technology Projects of Shaoxing City,No.2022KY104.
文摘BACKGROUND Diabetic cardiomyopathy(DCM)is the leading cause of cardiovascular diseaserelated mortality.Farrerol(FA)possesses anti-inflammatory and antioxidant properties.However,its role in regulating endothelial ferroptosis in DCM remains unknown.AIM To investigate the beneficial effects of FA on cardiac microvascular dysfunction in DCM from the perspective of ferroptosis in endothelial cells(ECs).METHODS The mice were fed a high-fat diet and injected with streptozotocin to induce DCM.DCM mice were orally administered FA(10 and 40 mg/kg/day)and a tail vein injection of the miR-29b-3p mimic or inhibitor for 24 weeks.Cardiac function and myocardial fibrosis were also analyzed.Cardiac microvascular function was assessed using immunofluorescence and transmission electron microscopy.Ferroptosis was analyzed using RNA sequencing,immunofluorescence,and western blotting.RESULTS FA administration improved cardiac function,alleviated myocardial fibrosis,strengthened endothelial barrier function,suppressed endothelial inflammation,and preserved the microvascular structure in DCM mice.This improvement was associated with the inhibition of endothelial ferroptosis and downregulation of miR-29b-3p in ECs.Similar efficacy was observed after tail vein injection of the miR-29b-3p inhibitor.Inhibition of miR-29b-3p in vivo showed an anti-cardiac fibrotic effect by improving microvascular dysfunction and ferroptosis in ECs,whereas overexpression of miR-29b-3p showed the opposite effects in DCM mice.Luciferase reporter assay revealed that miR-29b-3p binds to SIRT1.In cultured ECs,FA reduced high glucose and free fatty acid(HG/FFA)-induced lipid peroxidation and ferroptosis and inhibited endothelial-mediated inflammation.However,the overexpression of miR-29b-3p partially abolished the protective effects of FA against HG/FFA-induced injury in ECs.This finding suggests that the mechanism of action of FA in improving DCM is related to the downregulation of miR-29b-3p and activation of SIRT1 expression.CONCLUSION Therefore,FA has a potential therapeutic effect on cardiac microvascular dysfunction by suppressing EC ferroptosis through the miR-29b-3p/SIRT1 axis.
基金supported by the National Natural Science Foundation of China(Grant No.82270892)Natural Science Foundation of Hubei Province(Grant No.2022CFB287)+2 种基金Xianning City Science and Technology Plan Project(Grant No.2022ZRKX052)School projects of Hubei University of Science and Technology(Grant No.2022T01,2021WG05,2021TNB01)Hubei University of Science and Technology School-level Fund(Grant No.BK202122).
文摘Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary ammonium alkaloid isolated from Coptidis Rhizoma,a traditional Chinese medicine,has superior anti-diabetic and heart-protective properties.The purpose of this study is to assess the impact of BBR on DCM.Methods:This study used a systems pharmacology approach to evaluate the related proteins and signalling pathways between BBR and DCM targets,combined with experimental validation using diabetic mouse heart sections.Microstructural and pathological changes were observed using Hematoxylin-eosin,Masson’s trichrome stain and wheat germ agglutinin staining.Immunofluorescence and western blot were used to determine protein expression.Results:The results indicate that BBR and DCM share 21 core relevant targets,with cross-targets predominantly located in mitochondrial,endoplasmic reticulum,and plasma membrane components.BBR exerts its main effects in improving DCM by maintaining mitochondrial integrity,particularly involving the PI3K-AKT-GSK3βand apoptosis signalling pathways.In addition,post-treatment changes in the key targets of BBR,including cysteine aspartate specific protease(Caspase)-3,phosphoinositide 3-kinase(PI3K)and mitochondria-related proteins,are suggestive of its efficacy.Conclusion:BBR crucially improves DCM by maintaining mitochondrial integrity,inhibiting apoptosis,and modulating PI3K-AKT-GSK3βsignaling.Further studies must address animal model limitations and validate clinical efficacy to understand BBR’s mechanisms fully and its potential clinical use.
基金supported by Dongguan Social Development Science and Technology Program(No.202218009016172)。
文摘Background Diabetic cardiomyopathy(DCM)represents a severe cardiovascular complication of diabetes mellitus,characterized by insidious onset,diagnostic challenges in early stages,and poor prognosis.Current diagnosis of DCM primarily relies on imaging techniques,lacking convenient and effective early biomarkers.Method Using a case-control study design,we enrolled 50 DCM patients(DCM group)and 50 diabetes-only patients(control group)diagnosed at our hospital between January 2023 and January 2025.Demographic data were collected from all participants.Serum levels of hemoglobinA1c(HbAlc),interleukin-1β(IL-1β),and superoxide dismutase(SOD)were measured and compared between groups.Logistic regression analysis was performed to identify DCM risk factors,while receiver operating characteristic(ROC)curve analysis evaluated the diagnostic value of individual and combined biomarkers for DCM screening.Results The levels of HbAlc and IL-1βin the DCM group were higher than those in the control group,and the level of SOD was lower than that in the control group(P<0.05).Multivariate Logistic regression analysis showed that HbAlc,IL-1βand SOD were all independent risk factors for DCM.The results of the ROC curve showed that the areas under curve(AUC)of HbA1c,IL-1β,and SOD levels in diagnosing DCM patients were 0.673,0.783,and 0.728,respectively.The AUC predicted by the combination of the three was 0.836,which was higher than that detected by any above single index(P<0.05).Conclusions DCM patients exhibited significantly higher HbAlc and IL-1βlevels but lower SOD activity compared to the controls.Each biomarker demonstrated significant diagnostic value for DCM,and their combination yielded superior diagnostic performance compared to any single marker.
基金Project supported by the Scientific and Technological Projects for Medicine and Health of Zhejiang Province(No.2015128660)the Major Research and Development Projects for the Zhejiang Science and Technology Agency(No.2017C03034),China
文摘Objective： To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyo- pathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. Methods： Sixty Sprague-Dawley （SD） rats were randomly divided into six groups： a normal control group （NC）, an obesity group （OB）, a diabetic cardiomyopathy group （DCM）, a tea polyphenol group （TP）, an obesity tea polyphenol treatment group （OB-TP）, and a diabetic cardiomyopathy tea polyphenol treatment group （DCM-TP）. After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ul- trasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-11, SQSTM1/p62, and Beclin-1 were determined by Western blotting. Results： Com- pared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-11/I and Beclin-1 increased obviously whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups （P〈0.05）. Conclusions： Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.
文摘Diabetes mellitus(DM) is characterised by hyperglycemia, insulin resistance and metabolic dysregulation leading to diastolic and systolic dysfunction in diabetes. In this review, the pathogenetic and pathomorphological changes leading to diastolic and systolic dysfunction in diabetes are discussed. Changes in metabolic signalling pathways, mediators and effectors contribute to the pathogenesis of cardiac dysfunction in DM called diabetic cardiomyopathy(DC). Echocardiographic studies report on the association between DM and the presence of cardiac hypertrophy and myocardial stiffness that lead to diastolic dysfunction. More recently reported echocardiographic studies with more sensitive techniques, such as strain analysis, also observed systolic dysfunction as an early marker of DC. Depression of systolic and diastolic function is continuum and the line of separation is artificial. To conclude, according to current knowledge, DC is expected to be a common single phenotype that is caused by different pathogenetic and pathomorphological changes leading to diastolic and systolic dysfunction in diabetes.
基金supported by the first grade grant (No. 200070410129)the first batch special grant (No. 200801166) from China Postdoctoral Science Foundation+1 种基金the major project (No. H020920010330)the subject of Science and Technology Plan of Beijing Science and Technology Commission (No. D08050703020802)
文摘Objective:To study the effect of Shengmai San(生脉散Pulse-activating Powder) in protecting myocardium in the rat of the type 2 diabetic cardiomyopathy(DCM) model.Methods:The DCM rat model was established by combination of insulin resistance induced by a high-fat diet with intraperitoneal injection of high dose streptozotocin(50 mg/kg).And these rat models were randomly divided into three groups:a normal group(n=12,one of them died),a model group(n=15) and a Shengmai San group(treatment group,n=15).The damage of the myocardium was assessed by electrocardiogram at the twelfth week after modeling,and the blood glucose,cholesterol and triglyceride levels were determined;the content of the left cardiac ventricle myocardial collagen was quantified by Masson staining test;the level of myocardial cell apoptosis was detected with TUNEL apoptosis detection kit;the damage extent of the myocardial sub-cellular structures was observed by electron microscopy;the expression levels of cardiac TSP-1(Thrombospondin-1),TGF-β1(Transforming Growth Ffactor-β) and TRB-3(Tribbles homolog 3) proteins were detected by immunohistochemical method;the expression levels of cardiac TSP-1,A-TGF-β1 and L-TGF-β1 proteins were detected by Western blotting;and the expression levels of TSP-1 and TRB-3 mRNAs were detected by real-time quantitative PCR.Results:Compared with the control group,the blood glucose,cholesterol,triglycerides levels in both the model groups and the Shengmai San group were significantly decreased;the myocardial tissue was less damaged and the collagen content was reduced in the Shengmai San group;the myocardial sub-cellular structure was injured to a lesser extent;the expression levels of myocardial TSP-1,TGF-β1,TRB-3,and TSP-1,A-TGF-β1,L-TGF-β1 and chymase were decreased,and the expression levels of TSP-1 mRNA and TRB-3 mRNA were decreased in both the model groups and the Shengmai San group(the latter was better),.Conclusion:Shengmai San can inhibit myocardial fibrosis in the rat of diabetic cardiomyopathy,and significantly delay the formation of diabetic cardiomyopathy in hyperglycemia rats through multiple pathways.
基金Health Commission of Hebei Province,No.20210196S&T Program of Hebei,No.22377726D。
文摘BACKGROUND Diabetic cardiomyopathy(DCM)increases the risk of hospitalization for heart failure(HF)and mortality in patients with diabetes mellitus.However,no specific therapy to delay the progression of DCM has been identified.Mitochondrial dysfunction,oxidative stress,inflammation,and calcium handling imbalance play a crucial role in the pathological processes of DCM,ultimately leading to cardiomyocyte apoptosis and cardiac dysfunctions.Empagliflozin,a novel glucoselowering agent,has been confirmed to reduce the risk of hospitalization for HF in diabetic patients.Nevertheless,the molecular mechanisms by which this agent provides cardioprotection remain unclear.AIM To investigate the effects of empagliflozin on high glucose(HG)-induced oxidative stress and cardiomyocyte apoptosis and the underlying molecular mechanism.METHODS Twelve-week-old db/db mice and primary cardiomyocytes from neonatal rats stimulated with HG(30 mmol/L)were separately employed as in vivo and in vitro models.Echocardiography was used to evaluate cardiac function.Flow cytometry and TdT-mediated dUTP-biotin nick end labeling staining were used to assess apoptosis in myocardial cells.Mitochondrial function was assessed by cellular ATP levels and changes in mitochondrial membrane potential.Furthermore,intracellular reactive oxygen species production and superoxide dismutase activity were analyzed.Real-time quantitative PCR was used to analyze Bax and Bcl-2 mRNA expression.Western blot analysis was used to measure the phosphorylation of AMP-activated protein kinase(AMPK)and myosin phosphatase target subunit 1(MYPT1),as well as the peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)and active caspase-3 protein levels.RESULTSIn the in vivo experiment, db/db mice developed DCM. However, the treatment of db/db mice with empagliflozin(10 mg/kg/d) for 8 wk substantially enhanced cardiac function and significantly reduced myocardial apoptosis,accompanied by an increase in the phosphorylation of AMPK and PGC-1α protein levels, as well as a decrease inthe phosphorylation of MYPT1 in the heart. In the in vitro experiment, the findings indicate that treatment ofcardiomyocytes with empagliflozin (10 μM) or fasudil (FA) (a ROCK inhibitor, 100 μM) or overexpression of PGC-1α significantly attenuated HG-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis.However, the above effects were partly reversed by the addition of compound C (CC). In cells exposed to HG,empagliflozin treatment increased the protein levels of p-AMPK and PGC-1α protein while decreasing phosphorylatedMYPT1 levels, and these changes were mitigated by the addition of CC. Adding FA and overexpressingPGC-1α in cells exposed to HG substantially increased PGC-1α protein levels. In addition, no sodium-glucosecotransporter (SGLT)2 protein expression was detected in cardiomyocytes.CONCLUSION Empagliflozin partially achieves anti-oxidative stress and anti-apoptotic effects on cardiomyocytes under HGconditions by activating AMPK/PGC-1α and suppressing of the RhoA/ROCK pathway independent of SGLT2.
文摘Diabetic cardiomyopathy(DCM)is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and hypertension.As DCM is now recognized as a cause of substantial morbidity and mortality among patients with diabetes mellitus and clinical diagnosis is still inappropriate,various expert groups struggled to identify a suitable biomarker that will help in the recognition and management of DCM,with little success so far.Hence,we thought it important to address the role of biomarkers that have shown potential in either human or animal studies and which could eventually result in mitigating the poor outcomes of DCM.Among the array of biomarkers we thoroughly analyzed,long noncoding ribonucleic acids,soluble form of suppression of tumorigenicity 2 and galectin-3 seem to be most beneficial for DCM detection,as their plasma/serum levels accurately correlate with the early stages of DCM.The combination of relatively inexpensive and accurate speckle tracking echocardiography with some of the highlighted biomarkers may be a promising screening method for newly diagnosed diabetes mellitus type 2 patients.The purpose of the screening test would be to direct affected patients to more specific confirmation tests.This perspective is in concordance with current guidelines that accentuate the importance of an interdisciplinary team-based approach.
基金Supported by National Natural Science Foundation of China,No.82000276the Science and Technology Project of Jiangxi Provincial Health Commission,No.202310005.
文摘BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM development through the inflammatory response.Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes.Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.AIM To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.METHODS Streptozotocin was administered to induce diabetes in mice,followed by treatment with 30 mg/kg teneligliptin.RESULTS Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening,ejection fraction,and heart rate;increases in creatine kinase-MB(CK-MB),aspartate transaminase(AST),and lactate dehydrogenase(LDH)levels;and upregulated NADPH oxidase 4 were observed in diabetic mice,all of which were significantly reversed by teneligliptin.Moreover,NLRP3 inflammasome activation and increased release of interleukin-1βin diabetic mice were inhibited by teneligliptin.Primary mouse cardiomyocytes were treated with high glucose(30 mmol/L)with or without teneligliptin(2.5 or 5μM)for 24 h.NLRP3 inflammasome activation.Increases in CKMB,AST,and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin,and AMP(p-adenosine 5‘-monophosphate)-p-AMPK(activated protein kinase)levels were increased.Furthermore,the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.CONCLUSION Overall,teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.
基金Supported by National Natural Science Foundation of China,No.82000792General project of Chongqing Natural Science Foundation,No.cstc2020jcyj-msxm0409.
文摘In this editorial,we commented on the article published in the recent issue of the World Journal of Diabetes.Diabetic cardiomyopathy(DCM)is characterized by myocardial fibrosis,ventricular hypertrophy and diastolic dysfunction in diabetic patients,which can cause heart failure and threaten the life of patients.The pathogenesis of DCM has not been fully clarified,and it may involve oxidative stress,inflammatory stimulation,apoptosis,and autophagy.There is lack of effective therapies for DCM in the clinical practice.Statins have been widely used in the clinical practice for years mainly to reduce cholesterol and stabilize arterial plaques,and exhibit definite cardiovascular protective effects.Studies have shown that statins also have anti-inflammatory and antioxidant effects.We were particularly concerned about the recent findings that atorvastatin alleviated myocardial fibrosis in db/db mice by regulating the antioxidant stress and antiinflammatory effects of macrophage polarization on diabetic myocardium,and thereby improving DCM.
基金supported by the National Natural Science Foundation of China(Grant Nos.:21927808 and 81803483).
文摘Diabetic cardiomyopathy(DCM)is a metabolic disease and a leading cause of heart failure among people with diabetes.Mass spectrometry imaging(MSI)is a versatile technique capable of combining the molecular specificity of mass spectrometry(MS)with the spatial information of imaging.In this study,we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity.We optimized the air flow-assisted desorption electrospray ionization(AFADESI)-MSI platform to detect a wide range of metabolites,and then used matrix-assisted laser desorption ionization(MALDI)-MSI for increasing metabolic coverage and improving localization resolution.AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections,respectively,while MALDI-MSI detected 61 metabolites in negative analysis.Our study revealed the heterogenous metabolic profile of the heart in a DCM model,with over 105 region-specific changes in the levels of a wide range of metabolite classes,including carbohydrates,amino acids,nucleotides,and their derivatives,fatty acids,glycerol phospholipids,carnitines,and metal ions.The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model.Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.
文摘Diabetic complications,chiefly seen in long-term situations,are persistently deleterious to a large extent,requiring multi-factorial risk reduction strategies beyond glycemic control.Diabetic cardiomyopathy is one of the most common deleterious diabetic complications,being the leading cause of mortality among diabetic patients.The mechanisms of diabetic cardiomyopathy are multi-factorial,involving increased oxidative stress,accumulation of advanced glycation end products(AGEs),activation of various pro-inflammatory and cell death signaling pathways,and changes in the composition of extracellular matrix with enhanced cardiac fibrosis.The novel lipid signaling system,the endocannabinoid system,has been implicated in the pathogenesis of diabetes and its complications through its two main receptors:Cannabinoid receptor type 1 and cannabinoid receptor type 2,alongside other components.However,the role of the endocannabinoid system in diabetic cardiomyopathy has not been fully investigated.This review aims to elucidate the possible mechanisms through which cannabinoids and the endocannabinoid system could interact with the pathogenesis and the development of diabetic cardiomyopathy.These mechanisms include oxidative/nitrative stress,inflammation,accumulation of AGEs,cardiac remodeling,and autophagy.A better understanding of the role of cannabinoids and the endocannabinoid system in diabetic cardiomyopathy may provide novel strategies to manipulate such a serious diabetic complication.
文摘This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.
文摘Diabetic cardiomyopathy(DbCM)is a common but underrecognized complication of patients with diabetes mellitus(DM).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and cardiac autonomic neuropathy are mostly known with reasonable therapeutic options,the mechanisms and management options for DbCM are still not fully understood.In its early stages,DbCM presents with diastolic dysfunction followed by heart failure(HF)with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately managed.Apart from prompt control of DM with lifestyle changes and antidiabetic medications,disease-modifying therapy for DbCM includes prompt control of hypertension and dyslipidemia inherent to patients with DM as in other forms of heart diseases and the use of treatments with proven efficacy in HF.A basic study by Zhang et al,in a recent issue of the World Journal of Diabetes elaborates the potential pathophysiological alterations and the therapeutic role of teneligliptin in diabetic mouse models with DbCM.Although this preliminary basic study might help to improve our understanding of DbCM and offer a potential new management option for patients with the disease,the positive results from such animal models might not always translate to clinical practice as the pathobiology of DbCM in humans could be different.However,such experimental studies can encourage more scientific efforts to find a better solution to treat patients with this enigmatic disease.
文摘Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively investigated.However,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and pyroptosis.The direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific inhibitors.We thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific conditions.This editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent models.Only clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.
基金This research was funded by the Traditional Chinese Medicine and Integrative Medicine Research Project of Tianjin Administration of Traditional Chinese Medicine(2021192)the National Natural Science Foundation of China(NSFC,No.81970303)+2 种基金the Medical Health Science and Technology Project of the Health Commission of Tianjin(TJWJ2023QN026)the Natural Science Foundation of Tianjin(22JCQNJC01130)the Tianjin Key Medical Discipline(Specialty)Construction Project.
文摘Background:Diabetic cardiomyopathy is a multifaceted complication of diabetes that lacks effective treatments.Berberine(BBR),a bioactive compound from Rhizoma coptidis,has potential therapeutic implications,but its precise role in diabetic cardiomyopathy remains to be defined.Methods:In this study,a diabetic cardiomyopathy model was established by administration of a high-fat diet and streptozotocin injection to C57BL/6J mice.Concurrently,the mice received BBR treatment daily for a duration of 8 weeks.After the treatment period,myocardial injury,cardiac function,and the levels of oxidative stress and apoptosis were assessed.Results:BBR significantly ameliorated cardiac dysfunction and histopathological damage caused by diabetic cardio-myopathy.This treatment also elevated serum superoxide dismutase levels while decreasing malondialdehyde levels.The anti-apoptotic activity of BBR was evidenced by a decrease in TUNEL-positive cells and the percentage of apop-totic cells,as determined by flow cytometry,in conjunction with diminished levels of BCL2-associated X protein/B cell lymphoma 2(BAX/BCL2)in heart tissues.Mechanistically,BBR was found to ameliorate diabetic cardiomyopa-thy by upregulating the expression of myocardial methionine sulfoxide reductase A(MsrA)and concurrently suppress-ing cardiac CaMKII oxidation.Conclusions:BBR alleviates diabetic cardiomyopathy by inhibiting myocardial apoptosis and oxidative stress through the MsrA and CaMKII signaling pathways.
