The cardiac microenvironment profoundly restricts the efficacy of myocardial regeneration tactics for the treatment of myocardial infarction(MI).A prospective approach for MI therapeutics encompasses the combined stra...The cardiac microenvironment profoundly restricts the efficacy of myocardial regeneration tactics for the treatment of myocardial infarction(MI).A prospective approach for MI therapeutics encompasses the combined strategy of scavenging reactive oxygen species(ROS)to alleviate oxidative stress injury and facilitating macrophage polarization towards the regenerative M2 phenotype.In this investigation,we fabricated a ROSsensitive hydrogel engineered to deliver our previously engineered IL-1β-VHH for myocardial restoration.In mouse and rat models of myocardial infarction,the therapeutic gel was injected into the pericardial cavity,effectively disseminated over the heart surface,forming an in situ epicardial patch.The IL-1β-VHH released from the hydrogel exhibited penetrative potential into the myocardium.Our results imply that this infarct-targeting gel can adhere to the damaged cardiac tissue and augment the quantity of anti-IL-1βantibodies.Moreover,the anti-IL-1βhydrogel safeguards cardiomyocytes from apoptosis by neutralizing IL-1βand inducing M2-type polarization within the myocardial infarction regions,thereby facilitating therapeutic cardiac repair.Our results emphasize the effectiveness of this synergistic comprehensive treatment modality in the management of MI and showcase its considerable potential for promoting recovery in infarcted hearts.展开更多
There is a lack of human evidence concerning the cardiovascular effects of combined exposure to endocrine disruptors.This case-control study sought to investigate coronary heart disease(CHD)associations with exposure ...There is a lack of human evidence concerning the cardiovascular effects of combined exposure to endocrine disruptors.This case-control study sought to investigate coronary heart disease(CHD)associations with exposure to organophosphate flame retardants(OFRs),phthalates(PAEs),and polycyclic aromatic hydrocarbons(PAHs)among 148 adults with coronary-angiography-diagnosed CHD and 320 healthy adults from southern China.The mediating role of glucose-lipid metabolism was also explored.Bayesian kernel machine regression suggested that when exposure status was fixed to the 75th percentile with the median value as the reference,exposure to OFRs,PAEs,and PAHs was associated with an 84%(95%CI:36%−134%),132%(12%−252%),and 214%(89%−331%)increased risk of developing CHD,respectively.Weighted quantile sum regression indicated urinary bis(2-butoxyethyl)phosphate(BBOEP),dibutyl phosphate(DBP),monoisononyl phthalate(miNP),and metabolites of phenanthrene may be major contributors to the overall effect of mixtures.In further analyses on identified chemical risk factors,mediation analyses suggested exposure to phenanthrene may increase the risk of CHD via elevating total cholesterol and blood glucose,while exposure to DiNP mainly associates with serum lipids.Besides,we observed a slight mediation effect of oxidative DNA damage between urinary BBOEP and risk of CHD.These results provide potential direction for further experimental studies.Longitudinal evidence is needed to clarify the causation of the results.展开更多
Cardiovascular diseases(CVDs)remain the leading cause of morbidity and mortality worldwide.Recently,accumulating evidence has revealed hepatic mediators,termed as liverderived secretory factors(LDSFs),play an importan...Cardiovascular diseases(CVDs)remain the leading cause of morbidity and mortality worldwide.Recently,accumulating evidence has revealed hepatic mediators,termed as liverderived secretory factors(LDSFs),play an important role in regulating CVDs such as atherosclerosis,coronary artery disease,thrombosis,myocardial infarction,heart failure,metabolic cardiomyopathy,arterial hypertension,and pulmonary hypertension.LDSFs presented here consisted of microbial metabolite,extracellular vesicles,proteins,and microRNA,they are primarily or exclusively synthesized and released by the liver,and have been shown to exert pleiotropic actions on cardiovascular system.LDSFs mainly target vascular endothelial cell,vascular smooth muscle cells,cardiomyocytes,fibroblasts,macrophages and platelets,and further modulate endothelial nitric oxide synthase/nitric oxide,endothelial function,energy metabolism,inflammation,oxidative stress,and dystrophic calcification.Although some LDSFs are known to be detrimental/beneficial,controversial findings were also reported for many.Therefore,more studies are required to further explore the causal relationships between LDSFs and CVDs and uncover the exact mechanisms,which is expected to extend our understanding of the crosstalk between the liver and cardiovascular system and identify potential therapeutic targets.Furthermore,in the case of patients with liver disease,awareness should be given to the implications of these abnormalities in the cardiovascular system.These studies also underline the importance of early recognition and intervention of liver abnormalities in the practice of cardiovascular care,and a multidisciplinary approach combining hepatologists and cardiologists would be more preferable for such patients.展开更多
基金funded by The National Natural Science Foundation of China(NSFC)(82170256)Guangdong Major Project of Basic and Applied Basic Research(2023B0303000005)+3 种基金The National Key Research and Development Program of China(2018YFA0108700)Guangdong Provincial Special Support Program for Prominent Talents(2021JC06Y656)Science and Technology Planning Project of Guangdong Province(2022B1212010010)the Special Project of Dengfeng Program of Guangdong Provincial People’s Hospital(KJ012019119).
文摘The cardiac microenvironment profoundly restricts the efficacy of myocardial regeneration tactics for the treatment of myocardial infarction(MI).A prospective approach for MI therapeutics encompasses the combined strategy of scavenging reactive oxygen species(ROS)to alleviate oxidative stress injury and facilitating macrophage polarization towards the regenerative M2 phenotype.In this investigation,we fabricated a ROSsensitive hydrogel engineered to deliver our previously engineered IL-1β-VHH for myocardial restoration.In mouse and rat models of myocardial infarction,the therapeutic gel was injected into the pericardial cavity,effectively disseminated over the heart surface,forming an in situ epicardial patch.The IL-1β-VHH released from the hydrogel exhibited penetrative potential into the myocardium.Our results imply that this infarct-targeting gel can adhere to the damaged cardiac tissue and augment the quantity of anti-IL-1βantibodies.Moreover,the anti-IL-1βhydrogel safeguards cardiomyocytes from apoptosis by neutralizing IL-1βand inducing M2-type polarization within the myocardial infarction regions,thereby facilitating therapeutic cardiac repair.Our results emphasize the effectiveness of this synergistic comprehensive treatment modality in the management of MI and showcase its considerable potential for promoting recovery in infarcted hearts.
基金supported by the National Natural Science Foundation of China(42077385,42277424,82200435,and 82100451).
文摘There is a lack of human evidence concerning the cardiovascular effects of combined exposure to endocrine disruptors.This case-control study sought to investigate coronary heart disease(CHD)associations with exposure to organophosphate flame retardants(OFRs),phthalates(PAEs),and polycyclic aromatic hydrocarbons(PAHs)among 148 adults with coronary-angiography-diagnosed CHD and 320 healthy adults from southern China.The mediating role of glucose-lipid metabolism was also explored.Bayesian kernel machine regression suggested that when exposure status was fixed to the 75th percentile with the median value as the reference,exposure to OFRs,PAEs,and PAHs was associated with an 84%(95%CI:36%−134%),132%(12%−252%),and 214%(89%−331%)increased risk of developing CHD,respectively.Weighted quantile sum regression indicated urinary bis(2-butoxyethyl)phosphate(BBOEP),dibutyl phosphate(DBP),monoisononyl phthalate(miNP),and metabolites of phenanthrene may be major contributors to the overall effect of mixtures.In further analyses on identified chemical risk factors,mediation analyses suggested exposure to phenanthrene may increase the risk of CHD via elevating total cholesterol and blood glucose,while exposure to DiNP mainly associates with serum lipids.Besides,we observed a slight mediation effect of oxidative DNA damage between urinary BBOEP and risk of CHD.These results provide potential direction for further experimental studies.Longitudinal evidence is needed to clarify the causation of the results.
基金supported by the National Natural Science Foundation of China(No.82200435).
文摘Cardiovascular diseases(CVDs)remain the leading cause of morbidity and mortality worldwide.Recently,accumulating evidence has revealed hepatic mediators,termed as liverderived secretory factors(LDSFs),play an important role in regulating CVDs such as atherosclerosis,coronary artery disease,thrombosis,myocardial infarction,heart failure,metabolic cardiomyopathy,arterial hypertension,and pulmonary hypertension.LDSFs presented here consisted of microbial metabolite,extracellular vesicles,proteins,and microRNA,they are primarily or exclusively synthesized and released by the liver,and have been shown to exert pleiotropic actions on cardiovascular system.LDSFs mainly target vascular endothelial cell,vascular smooth muscle cells,cardiomyocytes,fibroblasts,macrophages and platelets,and further modulate endothelial nitric oxide synthase/nitric oxide,endothelial function,energy metabolism,inflammation,oxidative stress,and dystrophic calcification.Although some LDSFs are known to be detrimental/beneficial,controversial findings were also reported for many.Therefore,more studies are required to further explore the causal relationships between LDSFs and CVDs and uncover the exact mechanisms,which is expected to extend our understanding of the crosstalk between the liver and cardiovascular system and identify potential therapeutic targets.Furthermore,in the case of patients with liver disease,awareness should be given to the implications of these abnormalities in the cardiovascular system.These studies also underline the importance of early recognition and intervention of liver abnormalities in the practice of cardiovascular care,and a multidisciplinary approach combining hepatologists and cardiologists would be more preferable for such patients.
