Hypertrophic cardiomyopathy(HCM)is a primary myocardial disease characterized by myocardial hypertrophy,excluding other cardiovascular or systemic/metabolic causes of ventricular wall thickening.Apical hypertrophic ca...Hypertrophic cardiomyopathy(HCM)is a primary myocardial disease characterized by myocardial hypertrophy,excluding other cardiovascular or systemic/metabolic causes of ventricular wall thickening.Apical hypertrophic cardiomyopathy(ApHCM)represents a special form of ventricular hypertrophy predominantly affecting the left ventricular apex below the papillary muscles,typically without significant left ventricular outflow tract obstruction.[1,2]ApHCM often coexists with mild coronary artery abnormalities,[3]and reports of acute myocardial infarction with coronary artery stenosis in ApHCM or HCM patients are uncommon.展开更多
Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating ...Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.展开更多
Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The ...Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The prevalence rate in the population is 1:500-1:200.This article mainly introduces the diagnostic criteria,pathological manifestations,and genetic basis of HCM,which is the leading cause of sudden death in adolescents and athletes due to exercise,with 60%-70%showing familial clustering.It also discusses the latest progress in the relationship between different genotypes and clinical phenotypes of HCM pa-tients.展开更多
Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Mole...Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Molecular-genetic studies have confirmed that the vast majority of HCM is caused by mutations in genes encoding sarcomere proteins.HCM has a relatively wide phenotypic heterogeneity,varying from asymptomatic to sudden cardiac death,because of the many different mutations and pathogenic genes underlying it.Many studies have explored the clinical symptoms and prognosis of HCM,emphasizing the importance of genotype in evaluating patient prognosis and guiding the clinical management of HCM.To elaborate the main pathogenic genes and phenotypic prognosis in HCM to promote a better understanding of this genetic disease.Retrospective analysis of literature to evaluate the association between underlying gene mutations and clinical phenotypes in HCM patients.As sequencing technology advances,the pathogenic gene mutation spectrum and phenotypic characteristics of HCM are gradually becoming clearer.HCM is a widespread inherited disease with a highly variable clinical phenotype.The precise mechanisms linking known pathogenic gene mutations and the clinical course of this heterogeneous condition remain elusive.展开更多
BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress ...BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress to a dilated phase of HCM(DPHCM),which is associated with a poor prognosis;however,the underlying pathogenesis remains inadequately understood.CASE SUMMARY In this study,we present a case involving a pedigree with familial DPHCM and conduct a retrospective review of patients with DPHCM with identified gene mutations.Through panel sequencing targeting the coding regions of 312 genes associated with inherited cardiomyopathy,a heterozygous missense mutation(c.746G>A,p.Arg249Glu)in the MYH7 gene was identified in the proband(III-5).Sanger sequencing subsequently confirmed this pathogenic mutation in three additional family members(II-4,III-4,and IV-3).A total of 26 well-documented patients with DPHCM were identified in the literature.Patients with DPHCM are commonly middle-aged and male.The mean age of patients with DPHCM was 53.43±12.79 years.Heart failure,dyspnoea,and atrial fibrillation were the most prevalent symptoms observed,accompanied by an average left ventricular end-diastolic size of 58.62 mm.CONCLUSION Our findings corroborate the pathogenicity of the MYH7(c.746G>A,p.Arg249Glu)mutation for DPHCM and suggest that the Arg249Gln mutation may be responsible for high mortality.展开更多
BACKGROUND Hypertrophic cardiomyopathy(HCM)is characterized by left ventricular hypertrophy and interstitial fibrosis,which contribute to adverse outcomes such as heart failure and sudden cardiac death.While cardiac m...BACKGROUND Hypertrophic cardiomyopathy(HCM)is characterized by left ventricular hypertrophy and interstitial fibrosis,which contribute to adverse outcomes such as heart failure and sudden cardiac death.While cardiac magnetic resonance(CMR)imaging is commonly used to detect myocardial fibrosis,circulating microRNAs(miRNAs)have emerged as promising noninvasive biomarkers for this condition due to their stability in blood plasma and resistance to pH and temperature variance.AIM To explore the role of specific circulating miRNAs in identifying myocardial fibrosis in patients with HCM.METHODS Using PubMed/MEDLINE and Google Scholar,we reviewed studies from 2014 to 2024 examining the link between circulating miRNAs and myocardial fibrosis in HCM.We included studies measuring miRNA expression in blood samples from HCM patients and assessing fibrosis via imaging,mostly CMR.Data extraction concentrated on the population,methodology,and findings related to the correlation between miRNA levels and fibrosis.RESULTS Seven studies involving 365 HCM patients with a mean age of 49.37±10.5 years,116(31.78%)females,and one animal study identified miR-21,miR-29a,miR-133,miR-4454,and miR-221 as frequently dysregulated markers associated with fibrosis.Elevated levels of miR-21 and miR-29a correlated with more extensive fibrosis,as assessed by late gadolinium enhancement in CMR imaging,with miR-29a consistently linked to both fibrosis and hypertrophy across the studies.CONCLUSION Circulating miRNAs,particularly miR-21,miR-29a,and miR-221,show significant potential as biomarkers for myocardial fibrosis in HCM.Further research should validate these findings and investigate the clinical application of miRNA-based diagnostics in HCM.展开更多
Hypertrophic scars(HS)are fibrotic proliferative diseases that develop after deep skin injuries caused by trauma,burns,and surgery.Traditional treatment methods include both surgical and nonsurgical therapies.Early in...Hypertrophic scars(HS)are fibrotic proliferative diseases that develop after deep skin injuries caused by trauma,burns,and surgery.Traditional treatment methods include both surgical and nonsurgical therapies.Early intervention and combination therapy tailored to the individual needs of the patients are crucial for achieving optimal results.Three-dimensional(3D)printing technology,a rapid prototyping technique,is increasingly being applied in the medical field.The customization and precise functionality of 3D printing technology are particularly important for the rehabilitation of HS.This review provides an overview of HS and the role of 3D printing technology in medical applications,analyses the application of 3D-printed rehabilitation aids for HS,and discusses the use of 3D printing technology to improve HS treatment outcomes,thereby providing clinical guidance for effective HS rehabilitation.展开更多
To improve the treatment effect of obstructive hypertrophic cardiomyopathy,this article focuses on the treatment of obstructive hypertrophic cardiomyopathy and conducts a comprehensive analysis of the disease.It highl...To improve the treatment effect of obstructive hypertrophic cardiomyopathy,this article focuses on the treatment of obstructive hypertrophic cardiomyopathy and conducts a comprehensive analysis of the disease.It highlights the limitations of traditional treatment methods and elaborates on interventional and surgical treatments.Additionally,this article compares the indications,risks,treatment effects,and costs of the two different treatment methods,providing a reference for doctors and patients in selecting clinical treatment plans.展开更多
Background Hypertrophic obstructive cardiomyopathy(HOCM)is one of the main reasons for sudden cardiac death(SCD)in young people.Researches has revealed that immune-related genes are closely relevant to HOCMprogression...Background Hypertrophic obstructive cardiomyopathy(HOCM)is one of the main reasons for sudden cardiac death(SCD)in young people.Researches has revealed that immune-related genes are closely relevant to HOCMprogression.Therefore,it is important to explore the key immuneregulatory mechanisms and biomarkersof HOCM progression.Methods The bioinformatics methods,including linear models for microarray analysis(LIMMA),protein-protein interaction(PPI)network,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)and CIBERSORT,were used to assess the key pathways and hub genes involved in HOCM.Furthermore,expression levels of hub genes were validatedin human tissue.Results Our results showed that the degree of infiltration of five immune cells was linked to HOCM progression,including monocytes,macrophages M2,natural killer(NK)cell resting,B cells native,and T cells regulatory(Tregs).A total of 7 hub genes(CCL2,CXCL8,FOS,MAP2K1,NFKBIA,STAT3,and TNFRSF1A)were identified and validated by quantitative real-time polymerase chain reaction(qt-PCR).The core genes including CCL2,MAP2K1,NFKBIA,STAT3,and TNFRSF1A are closely related to monocytes infiltration during HOCM progression.Conclusions Taken together,our research provided useful information to explore the immune mechanisms underlying HCM progression and to provide a potential therapeutic target for therapy in HOCM.The interactional relationship of GATA5,BCL3,and ATF1 complex-regulation CCL2,MAP2K1,NFKBIA,STAT3,and TNFRSF1A was involved in the regulation of monocytes tissue infiltration,which was closely related to the progression of HOCM.展开更多
Background:Hypertrophic scars and keloids,common complications following median sternotomy for cardiac surgery,significantly impact patient quality of life due to their aesthetic and symptomatic burden.Recent advanceme...Background:Hypertrophic scars and keloids,common complications following median sternotomy for cardiac surgery,significantly impact patient quality of life due to their aesthetic and symptomatic burden.Recent advancements in laser therapy have made it a prominent option for managing these complex scars,yet a com-prehensive understanding of its efficacy is lacking.The aim of this scoping review is to explore the effects of laser therapy in managing hypertrophic scars and keloids after median sternotomy.Methods:This scoping review ana-lyzed studies up to February 2024 from databases including PubMed,EMBASE,CINAHL,Scopus,Web of Science,and the Cochrane Library.We included any study that assessed laser therapy’s effects on hypertrophic scars and keloids following median sternotomy.Studies were selected based on predefined inclusion criteria with-out publication year,design,or origin restrictions.Results:Six studies met the inclusion criteria,involving a total offive RCTs and one review.These studies primarily tested 585 and 595-nm pulsed dye laser(PDL)treatments,focusing on scar appearance,patient symptoms,and treatment satisfaction.Most studies reported significant improvements in scar height reduction and patient symptom relief after treatment,with mixed results for scar erythema and elasticity.Adverse events were generally mild and transient.Conclusions:Laser therapy offers a beneficial approach for improving the appearance and symptoms of hypertrophic scars and keloids post-median sternotomy.However,further research is necessary to optimize treatment parameters and explore the long-term psychosocial impacts of this therapy.This review highlights the need for more comprehensive studies to establish standardized treatment protocols and evaluate their effectiveness.展开更多
BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be e...BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.展开更多
Hypertrophic cardiomyopathy(HCM)is a genetically determined myocardial disease characterized by an increased thickness of the left ventricle(LV)wall that cannot be solely attributed to abnormal loading conditions.HCM ...Hypertrophic cardiomyopathy(HCM)is a genetically determined myocardial disease characterized by an increased thickness of the left ventricle(LV)wall that cannot be solely attributed to abnormal loading conditions.HCM may present with an intraventricular or LV outflow tract obstruction,diastolic dysfunction,myocardial fibrosis and/or ventricular arrhythmias.Differentiating HCM from other diseases associated with LV hypertrophy,such as hypertension,aortic stenosis,or LV non-compaction(LVNC),can at times be challenging.LVNC is defined by excessive LV trabeculation and deep recesses between trabeculae,often accompanied by increased LV myocardial mass.Previous studies indicate that the LVNC phenotype may be observed in up to 5%of the general population;however,in most cases,it is a benign finding with no impact on clinical outcomes.Nevertheless,LVNC can occasionally lead to LV systolic dysfunction,manifesting as a phenotype of dilated or non-dilated left ventricular cardiomyopathy,with an increased risk of thrombus formation and arterial embolism.In extreme cases,where LVNC is associated with a very thickened LV wall,it can even mimic HCM.There is growing evidence of an overlap between HCM and LVNC,including similar genetic mutations and clinical presentations.This raises the question of whether HCM and LVNC represent different phenotypes of the same disease or are,in fact,two distinct entities.展开更多
Background:Previous studies combined integrated scRNA-seq with bulk RNAdata to screen biomarkers for cardiomyopathy.This study extended this approach to identify biomarkers specific for hypertrophic cardiomyopathy(HCM...Background:Previous studies combined integrated scRNA-seq with bulk RNAdata to screen biomarkers for cardiomyopathy.This study extended this approach to identify biomarkers specific for hypertrophic cardiomyopathy(HCM).Methods:Datasets GSE36961,GSE130036,GSE249925 and GSE203274 were analyzed in this study.ScRNA-seq analysis was employed to identify distinct cell populations.Differentially expression analysis was conducted to screen vascular endothelial cells(VECs)-related feature genes.After calculating VECs score,WGCNA was used to correlate gene modules with the VECs score.Key HCM biomarkers were determined using random forest analysis,and LASSO regression analyses to construct a diagnostic model based on their diagnostic efficacy and differential expression.Results:Our analysis identified nine distinct cell populations,with VECs accounting for a notably higher proportion in HCM samples.Genes associated with the VECs were enriched in the pathways related to blood vessel,immunity and cardiac function.After classifying significant gene modules based on VEC-related genes,a strong correlation between the blue module and the VECs score was detected.Notably,genes in the blue module were enriched in the pathways related tometabolism andimmune response.Key geneswith a high expression in HCM were determined by intersecting differentially expressed genes(DEGs)in HCM with those in the bluemodule.Finally,randomforest analysis and LASSO regression analysis identified five central hub genes for the diagnosis of HCM,including Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1B(DYRK1B),Growth Arrest and DNA Damage Inducible Alpha(GADD45A),Influenza Virus NS1A Binding Protein(IVNS1ABP),Leiomodin 2(LMOD2),and Pleckstrin Homology Like Domain Family B Member 2(PHLDB2).Conclusion:Collectively,our study discovered novel VEC-related biomarkers for HCM and comprehensively examined the mechanisms underlying the pathogenesis of HCM.展开更多
BACKGROUND Apical hypertrophic cardiomyopathy(AHCM)is a subtype of hypertrophic cardiomyopathy.Due to its location,the thickening of the left ventricular apex can be missed on echocardiography.Giant negative T waves(G...BACKGROUND Apical hypertrophic cardiomyopathy(AHCM)is a subtype of hypertrophic cardiomyopathy.Due to its location,the thickening of the left ventricular apex can be missed on echocardiography.Giant negative T waves(GNTs)in left-sided chest leads are the hallmark electrocardiogram(ECG)change of AHCM.CASE SUMMARY The first patient was a 68-year-old woman complaining of recurrent chest tightness persisting for more than 3 years.The second was a 59-year-old man complaining of spasmodic chest tightness persisting for more than 2 years.The third was a 55-year-old woman complaining of recurrent chest pain persisting for 4 mo.In all three cases,GNTs were observed several years prior to apical cardiac hypertrophy after other causes of T-wave inversion were ruled out.CONCLUSION Electrophysiological abnormalities of AHCM appear earlier than structural abnormalities,confirming the early predictive value of ECG for AHCM.展开更多
BACKGROUND Immunoglobulin G4 related disease(Ig G4-RD)is a fibroinflammatory disease with markedly elevated serum Ig G4 levels and fibrous tissue proliferation,accompanied by numerous plasma cells.Ig G4 related hypert...BACKGROUND Immunoglobulin G4 related disease(Ig G4-RD)is a fibroinflammatory disease with markedly elevated serum Ig G4 levels and fibrous tissue proliferation,accompanied by numerous plasma cells.Ig G4 related hypertrophic pachymeningitis(Ig G4-RHP)is relatively rare and indistinguishable from other phymatoid diseases before the operation.The risk of long-term immunosuppression needs to be balanced with disease activity.CASE SUMMARY A 40-year-old man presented with headache and bilateral abducent paralysis.He was also diagnosed with pulmonary tuberculosis 10 years ago and was on regular treatment for the same.Before the operation and steroid therapy,the patient was suspected of having tubercular meningitis at a local hospital.A clivus lesion was found via brain magnetic resonance imaging(MRI)at this presentation.He was preliminarily diagnosed with meningioma and underwent Gamma Knife Surgery.Transnasal endoscopic resection was performed to treat deterioration of nerve function.Postoperative pathologic examination suggested Ig G4-RD.Moreover,the serum Ig G4 was elevated at 1.90 g/L(reference range:0.035-1.500 g/L).After steroid therapy for 2 mo,the lesion size diminished on MRI,and the function of bilateral abducent nerves recovered.CONCLUSION Ig G4-RHP is relatively rare and indistinguishable before the operation.Elevated serum Ig G4 levels and imaging examination help in the diagnosis of Ig G4-RHP.Surgery is necessary when lesions progress and patients start to develop cranial nerve function deficit.展开更多
Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein...Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein expression levels of Beclin-1,p62,and LC3II in normal skin tissues and HS specimens from different patients were examined.Autophagy inducers and inhibitors were used to cure established HS in rabbit ears,and the expression of Beclin-1,p62,and LC3II at the RNA and protein level was determined.Lastly,the effects of autophagy inducers and inhibitors on HS development were analyzed.Results:Compared to normal skin tissues,the expression of LC3II and Beclin-1 was higher(P<0.05),while that of p62 was lower(P<0.05)in HS tissues.In addition,the LC3II/LC3I ratio was increased during HS formation,and the altered expression of the three proteins stabilized after one year.Administration of autophagy inducers enhanced the formation of HS as well as the expression levels of LC3II and Beclin-1 but decreased p62 expression.Meanwhile,administration of autophagy inhibitors increased the expression of LC3II,Beclin-1,and p62,along with reduced HS formation.Conclusion:Autophagic activity increased during HS initiation and subsequent stabilization.In addition,autophagy inhibitors were able to inhibit HS formation by suppressing autophagy,whereas autophagy inducers promoted scar hyperplasia by enhancing autophagy。展开更多
Objective： The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods： Eight male New Zealand wh...Objective： The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods： Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed （about 15 d post wounding）. For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding. Results： Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 （p〈0.05）. Scar thickness, measured by scar elevation index （SEI） at Day 35 post wounding, was significantly reduced in the intervention group （1.09±0.19） compared with the controls （1.36±0.28）. Microvessel density （MVD） observed in the intervention group （1.73±0.94） was significantly lower than that of the control group （5.63±1.78） on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin. Conclusions： Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-dedved growth factor （PDGF） and fibroblast growth factor （FGF）, thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.展开更多
Hypertrophic cardiomyopathy(HCM),the most variable cardiac disease in terms of phenotypic presentation and clinical outcome,represents the most common inherited cardiomyopathic process with an autosomal dominant trait...Hypertrophic cardiomyopathy(HCM),the most variable cardiac disease in terms of phenotypic presentation and clinical outcome,represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance.To date,more than 1400 mutations of myofilament proteins associated with the disease have been identified,most of them "private" ones.This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations.Additionally,topics pertaining to patients' everyday lives,such as sudden cardiac death(SCD)risk stratification and prevention,along with disease prognosis,are grossly related to the genetic variation of HCM.This review incorporates contemporary research findings and addresses major aspects of HCM,including preclinical diagnosis,genetic analysis,left ventricular outflow tract obstruction and SCD.More specifically,the spectrum of genetic analysis,the selection of the best method for obstruction alleviation and the need for a unique and accuratefactor for SCD risk stratification are only some of the controversial HCM issues discussed.Additionally,future perspectives concerning HCM and myocardial ischemia,as well as atrial fibrillation,are discussed.Rather than enumerating clinical studies and guidelines,challenging problems concerning the disease are critically appraised by this review,highlighting current speculations and recommending future directions.展开更多
Apical hypertrophic cardiomyopathy(AHCM) is a relatively rare morphologic variant of HCM in which the hypertrophy of myocardium is localized to the left ventricular apex. Symptoms of AHCM might vary from none to other...Apical hypertrophic cardiomyopathy(AHCM) is a relatively rare morphologic variant of HCM in which the hypertrophy of myocardium is localized to the left ventricular apex. Symptoms of AHCM might vary from none to others mimic coronary artery disease including acute coronary syndrome, thus resulting in inappropriate hospitalization. Transthoracic echocardiography is the firstline imaging technique for the diagnosis of hypertrophic cardiomyopathies. However, when the hypertrophy of the myocardium is localized in the ventricular apex might results in missed diagnosis. Aim of this paper is to review the different imaging techniques used for the diagnosis of AHCM and their role in the detection and comprehension of this uncommon disease.展开更多
AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy(HCM).METHODS We prospectively assessed 20 patient...AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy(HCM).METHODS We prospectively assessed 20 patients(mean age 53 ± 16 years,range:18-81 years,10 were male),with apical HCM. We measured global longitudinal peak systolic strain(GLPSS) in the midwall and endocardium of the left ventricle. RESULTS The diastolic thickness of the 4 apical segments was 16.25 ± 2.75 mm. All patients had a normal global systolicfunction with a fractional shortening of 50% ± 8%. In spite of supernormal left ventricular(LV) systolic function,midwall GLPSS was decreased in all patients,more in the apical(-7.3% ±-8.8%) than in basal segments(-15.5% ±-6.93%),while endocardial GLPPS was significantly greater and reached normal values(apical:-22.8% ±-7.8%,basal:-17.9% ±-7.5%). CONCLUSION This study shows that two-dimensional strain was decreased mainly confined to the mesocardium,while endocardium myocardial deformation was preserved in HCM and allowed to identify subclinical LV dysfunction. This transmural heterogeneity in systolic strain had not been previously described in HCM and could be explained by the distribution of myofibrillar disarray in deep myocardial areas. The clinical application of this novel finding may help further understanding of the pathophysiology of HCM.展开更多
文摘Hypertrophic cardiomyopathy(HCM)is a primary myocardial disease characterized by myocardial hypertrophy,excluding other cardiovascular or systemic/metabolic causes of ventricular wall thickening.Apical hypertrophic cardiomyopathy(ApHCM)represents a special form of ventricular hypertrophy predominantly affecting the left ventricular apex below the papillary muscles,typically without significant left ventricular outflow tract obstruction.[1,2]ApHCM often coexists with mild coronary artery abnormalities,[3]and reports of acute myocardial infarction with coronary artery stenosis in ApHCM or HCM patients are uncommon.
文摘Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.
基金Supported by National Natural Science Foundation of China,No.82230065,No.82371974 and No.82272009.
文摘Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The prevalence rate in the population is 1:500-1:200.This article mainly introduces the diagnostic criteria,pathological manifestations,and genetic basis of HCM,which is the leading cause of sudden death in adolescents and athletes due to exercise,with 60%-70%showing familial clustering.It also discusses the latest progress in the relationship between different genotypes and clinical phenotypes of HCM pa-tients.
基金Supported by National Natural Science Foundation of China,No.81770379 and 81470521.
文摘Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Molecular-genetic studies have confirmed that the vast majority of HCM is caused by mutations in genes encoding sarcomere proteins.HCM has a relatively wide phenotypic heterogeneity,varying from asymptomatic to sudden cardiac death,because of the many different mutations and pathogenic genes underlying it.Many studies have explored the clinical symptoms and prognosis of HCM,emphasizing the importance of genotype in evaluating patient prognosis and guiding the clinical management of HCM.To elaborate the main pathogenic genes and phenotypic prognosis in HCM to promote a better understanding of this genetic disease.Retrospective analysis of literature to evaluate the association between underlying gene mutations and clinical phenotypes in HCM patients.As sequencing technology advances,the pathogenic gene mutation spectrum and phenotypic characteristics of HCM are gradually becoming clearer.HCM is a widespread inherited disease with a highly variable clinical phenotype.The precise mechanisms linking known pathogenic gene mutations and the clinical course of this heterogeneous condition remain elusive.
基金Supported by National Natural Science Foundation of China,No.81770379.
文摘BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress to a dilated phase of HCM(DPHCM),which is associated with a poor prognosis;however,the underlying pathogenesis remains inadequately understood.CASE SUMMARY In this study,we present a case involving a pedigree with familial DPHCM and conduct a retrospective review of patients with DPHCM with identified gene mutations.Through panel sequencing targeting the coding regions of 312 genes associated with inherited cardiomyopathy,a heterozygous missense mutation(c.746G>A,p.Arg249Glu)in the MYH7 gene was identified in the proband(III-5).Sanger sequencing subsequently confirmed this pathogenic mutation in three additional family members(II-4,III-4,and IV-3).A total of 26 well-documented patients with DPHCM were identified in the literature.Patients with DPHCM are commonly middle-aged and male.The mean age of patients with DPHCM was 53.43±12.79 years.Heart failure,dyspnoea,and atrial fibrillation were the most prevalent symptoms observed,accompanied by an average left ventricular end-diastolic size of 58.62 mm.CONCLUSION Our findings corroborate the pathogenicity of the MYH7(c.746G>A,p.Arg249Glu)mutation for DPHCM and suggest that the Arg249Gln mutation may be responsible for high mortality.
文摘BACKGROUND Hypertrophic cardiomyopathy(HCM)is characterized by left ventricular hypertrophy and interstitial fibrosis,which contribute to adverse outcomes such as heart failure and sudden cardiac death.While cardiac magnetic resonance(CMR)imaging is commonly used to detect myocardial fibrosis,circulating microRNAs(miRNAs)have emerged as promising noninvasive biomarkers for this condition due to their stability in blood plasma and resistance to pH and temperature variance.AIM To explore the role of specific circulating miRNAs in identifying myocardial fibrosis in patients with HCM.METHODS Using PubMed/MEDLINE and Google Scholar,we reviewed studies from 2014 to 2024 examining the link between circulating miRNAs and myocardial fibrosis in HCM.We included studies measuring miRNA expression in blood samples from HCM patients and assessing fibrosis via imaging,mostly CMR.Data extraction concentrated on the population,methodology,and findings related to the correlation between miRNA levels and fibrosis.RESULTS Seven studies involving 365 HCM patients with a mean age of 49.37±10.5 years,116(31.78%)females,and one animal study identified miR-21,miR-29a,miR-133,miR-4454,and miR-221 as frequently dysregulated markers associated with fibrosis.Elevated levels of miR-21 and miR-29a correlated with more extensive fibrosis,as assessed by late gadolinium enhancement in CMR imaging,with miR-29a consistently linked to both fibrosis and hypertrophy across the studies.CONCLUSION Circulating miRNAs,particularly miR-21,miR-29a,and miR-221,show significant potential as biomarkers for myocardial fibrosis in HCM.Further research should validate these findings and investigate the clinical application of miRNA-based diagnostics in HCM.
基金supported by the Cross-Disciplinary Research Fund Project of the Shanghai Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine(grant no.JYJC202236)the Shanghai Plastic Surgery Research Center of Shanghai Priority Research Center(grant no.2023ZZ02023)the Shanghai Healthcare System Key Supporting Disciplines Program(grant no.2023ZDFC0303).
文摘Hypertrophic scars(HS)are fibrotic proliferative diseases that develop after deep skin injuries caused by trauma,burns,and surgery.Traditional treatment methods include both surgical and nonsurgical therapies.Early intervention and combination therapy tailored to the individual needs of the patients are crucial for achieving optimal results.Three-dimensional(3D)printing technology,a rapid prototyping technique,is increasingly being applied in the medical field.The customization and precise functionality of 3D printing technology are particularly important for the rehabilitation of HS.This review provides an overview of HS and the role of 3D printing technology in medical applications,analyses the application of 3D-printed rehabilitation aids for HS,and discusses the use of 3D printing technology to improve HS treatment outcomes,thereby providing clinical guidance for effective HS rehabilitation.
文摘To improve the treatment effect of obstructive hypertrophic cardiomyopathy,this article focuses on the treatment of obstructive hypertrophic cardiomyopathy and conducts a comprehensive analysis of the disease.It highlights the limitations of traditional treatment methods and elaborates on interventional and surgical treatments.Additionally,this article compares the indications,risks,treatment effects,and costs of the two different treatment methods,providing a reference for doctors and patients in selecting clinical treatment plans.
基金National Natural Science Foundation of China(No.82102955)Guangzhou Basic Research Project(No.02201011326)。
文摘Background Hypertrophic obstructive cardiomyopathy(HOCM)is one of the main reasons for sudden cardiac death(SCD)in young people.Researches has revealed that immune-related genes are closely relevant to HOCMprogression.Therefore,it is important to explore the key immuneregulatory mechanisms and biomarkersof HOCM progression.Methods The bioinformatics methods,including linear models for microarray analysis(LIMMA),protein-protein interaction(PPI)network,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)and CIBERSORT,were used to assess the key pathways and hub genes involved in HOCM.Furthermore,expression levels of hub genes were validatedin human tissue.Results Our results showed that the degree of infiltration of five immune cells was linked to HOCM progression,including monocytes,macrophages M2,natural killer(NK)cell resting,B cells native,and T cells regulatory(Tregs).A total of 7 hub genes(CCL2,CXCL8,FOS,MAP2K1,NFKBIA,STAT3,and TNFRSF1A)were identified and validated by quantitative real-time polymerase chain reaction(qt-PCR).The core genes including CCL2,MAP2K1,NFKBIA,STAT3,and TNFRSF1A are closely related to monocytes infiltration during HOCM progression.Conclusions Taken together,our research provided useful information to explore the immune mechanisms underlying HCM progression and to provide a potential therapeutic target for therapy in HOCM.The interactional relationship of GATA5,BCL3,and ATF1 complex-regulation CCL2,MAP2K1,NFKBIA,STAT3,and TNFRSF1A was involved in the regulation of monocytes tissue infiltration,which was closely related to the progression of HOCM.
文摘Background:Hypertrophic scars and keloids,common complications following median sternotomy for cardiac surgery,significantly impact patient quality of life due to their aesthetic and symptomatic burden.Recent advancements in laser therapy have made it a prominent option for managing these complex scars,yet a com-prehensive understanding of its efficacy is lacking.The aim of this scoping review is to explore the effects of laser therapy in managing hypertrophic scars and keloids after median sternotomy.Methods:This scoping review ana-lyzed studies up to February 2024 from databases including PubMed,EMBASE,CINAHL,Scopus,Web of Science,and the Cochrane Library.We included any study that assessed laser therapy’s effects on hypertrophic scars and keloids following median sternotomy.Studies were selected based on predefined inclusion criteria with-out publication year,design,or origin restrictions.Results:Six studies met the inclusion criteria,involving a total offive RCTs and one review.These studies primarily tested 585 and 595-nm pulsed dye laser(PDL)treatments,focusing on scar appearance,patient symptoms,and treatment satisfaction.Most studies reported significant improvements in scar height reduction and patient symptom relief after treatment,with mixed results for scar erythema and elasticity.Adverse events were generally mild and transient.Conclusions:Laser therapy offers a beneficial approach for improving the appearance and symptoms of hypertrophic scars and keloids post-median sternotomy.However,further research is necessary to optimize treatment parameters and explore the long-term psychosocial impacts of this therapy.This review highlights the need for more comprehensive studies to establish standardized treatment protocols and evaluate their effectiveness.
基金Supported by the 2022 Shaoxing City Health Science and Technology Program(Health Science and Technology Program),No.2022KY050。
文摘BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.
基金Supported by The Department of Scientific Research and Structural Funds of Medical College,Jagiellonian University,No.N41/DBS/000594.
文摘Hypertrophic cardiomyopathy(HCM)is a genetically determined myocardial disease characterized by an increased thickness of the left ventricle(LV)wall that cannot be solely attributed to abnormal loading conditions.HCM may present with an intraventricular or LV outflow tract obstruction,diastolic dysfunction,myocardial fibrosis and/or ventricular arrhythmias.Differentiating HCM from other diseases associated with LV hypertrophy,such as hypertension,aortic stenosis,or LV non-compaction(LVNC),can at times be challenging.LVNC is defined by excessive LV trabeculation and deep recesses between trabeculae,often accompanied by increased LV myocardial mass.Previous studies indicate that the LVNC phenotype may be observed in up to 5%of the general population;however,in most cases,it is a benign finding with no impact on clinical outcomes.Nevertheless,LVNC can occasionally lead to LV systolic dysfunction,manifesting as a phenotype of dilated or non-dilated left ventricular cardiomyopathy,with an increased risk of thrombus formation and arterial embolism.In extreme cases,where LVNC is associated with a very thickened LV wall,it can even mimic HCM.There is growing evidence of an overlap between HCM and LVNC,including similar genetic mutations and clinical presentations.This raises the question of whether HCM and LVNC represent different phenotypes of the same disease or are,in fact,two distinct entities.
基金supported by Technology Project of Nantong Municipal Health Commission(grant number MSZ2022045).
文摘Background:Previous studies combined integrated scRNA-seq with bulk RNAdata to screen biomarkers for cardiomyopathy.This study extended this approach to identify biomarkers specific for hypertrophic cardiomyopathy(HCM).Methods:Datasets GSE36961,GSE130036,GSE249925 and GSE203274 were analyzed in this study.ScRNA-seq analysis was employed to identify distinct cell populations.Differentially expression analysis was conducted to screen vascular endothelial cells(VECs)-related feature genes.After calculating VECs score,WGCNA was used to correlate gene modules with the VECs score.Key HCM biomarkers were determined using random forest analysis,and LASSO regression analyses to construct a diagnostic model based on their diagnostic efficacy and differential expression.Results:Our analysis identified nine distinct cell populations,with VECs accounting for a notably higher proportion in HCM samples.Genes associated with the VECs were enriched in the pathways related to blood vessel,immunity and cardiac function.After classifying significant gene modules based on VEC-related genes,a strong correlation between the blue module and the VECs score was detected.Notably,genes in the blue module were enriched in the pathways related tometabolism andimmune response.Key geneswith a high expression in HCM were determined by intersecting differentially expressed genes(DEGs)in HCM with those in the bluemodule.Finally,randomforest analysis and LASSO regression analysis identified five central hub genes for the diagnosis of HCM,including Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1B(DYRK1B),Growth Arrest and DNA Damage Inducible Alpha(GADD45A),Influenza Virus NS1A Binding Protein(IVNS1ABP),Leiomodin 2(LMOD2),and Pleckstrin Homology Like Domain Family B Member 2(PHLDB2).Conclusion:Collectively,our study discovered novel VEC-related biomarkers for HCM and comprehensively examined the mechanisms underlying the pathogenesis of HCM.
文摘BACKGROUND Apical hypertrophic cardiomyopathy(AHCM)is a subtype of hypertrophic cardiomyopathy.Due to its location,the thickening of the left ventricular apex can be missed on echocardiography.Giant negative T waves(GNTs)in left-sided chest leads are the hallmark electrocardiogram(ECG)change of AHCM.CASE SUMMARY The first patient was a 68-year-old woman complaining of recurrent chest tightness persisting for more than 3 years.The second was a 59-year-old man complaining of spasmodic chest tightness persisting for more than 2 years.The third was a 55-year-old woman complaining of recurrent chest pain persisting for 4 mo.In all three cases,GNTs were observed several years prior to apical cardiac hypertrophy after other causes of T-wave inversion were ruled out.CONCLUSION Electrophysiological abnormalities of AHCM appear earlier than structural abnormalities,confirming the early predictive value of ECG for AHCM.
基金Supported by 1·3·5 Project for Disciplines of Excellence–Clinical Research Incubation Project,West China Hospital,Sichuan University,No.2019HXFH018。
文摘BACKGROUND Immunoglobulin G4 related disease(Ig G4-RD)is a fibroinflammatory disease with markedly elevated serum Ig G4 levels and fibrous tissue proliferation,accompanied by numerous plasma cells.Ig G4 related hypertrophic pachymeningitis(Ig G4-RHP)is relatively rare and indistinguishable from other phymatoid diseases before the operation.The risk of long-term immunosuppression needs to be balanced with disease activity.CASE SUMMARY A 40-year-old man presented with headache and bilateral abducent paralysis.He was also diagnosed with pulmonary tuberculosis 10 years ago and was on regular treatment for the same.Before the operation and steroid therapy,the patient was suspected of having tubercular meningitis at a local hospital.A clivus lesion was found via brain magnetic resonance imaging(MRI)at this presentation.He was preliminarily diagnosed with meningioma and underwent Gamma Knife Surgery.Transnasal endoscopic resection was performed to treat deterioration of nerve function.Postoperative pathologic examination suggested Ig G4-RD.Moreover,the serum Ig G4 was elevated at 1.90 g/L(reference range:0.035-1.500 g/L).After steroid therapy for 2 mo,the lesion size diminished on MRI,and the function of bilateral abducent nerves recovered.CONCLUSION Ig G4-RHP is relatively rare and indistinguishable before the operation.Elevated serum Ig G4 levels and imaging examination help in the diagnosis of Ig G4-RHP.Surgery is necessary when lesions progress and patients start to develop cranial nerve function deficit.
基金the National Natural Science Foundation of China(grant no.81872219)Science and Technology Project of Hunan Provincial Health Commission(grant no.B2015-040)+2 种基金Major Scientific and Technological Projects in Hunan Province(grant no.2019SK1010)2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant(grant nos.2020LKSFG18B,2020LKSFG02E)Guangdong University Innovation Team Project(grant no.2021KCXTD047).
文摘Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein expression levels of Beclin-1,p62,and LC3II in normal skin tissues and HS specimens from different patients were examined.Autophagy inducers and inhibitors were used to cure established HS in rabbit ears,and the expression of Beclin-1,p62,and LC3II at the RNA and protein level was determined.Lastly,the effects of autophagy inducers and inhibitors on HS development were analyzed.Results:Compared to normal skin tissues,the expression of LC3II and Beclin-1 was higher(P<0.05),while that of p62 was lower(P<0.05)in HS tissues.In addition,the LC3II/LC3I ratio was increased during HS formation,and the altered expression of the three proteins stabilized after one year.Administration of autophagy inducers enhanced the formation of HS as well as the expression levels of LC3II and Beclin-1 but decreased p62 expression.Meanwhile,administration of autophagy inhibitors increased the expression of LC3II,Beclin-1,and p62,along with reduced HS formation.Conclusion:Autophagic activity increased during HS initiation and subsequent stabilization.In addition,autophagy inhibitors were able to inhibit HS formation by suppressing autophagy,whereas autophagy inducers promoted scar hyperplasia by enhancing autophagy。
基金supported by the National Natural Science Foundation of China (No.81272120)the Health Department of the Zhejiang Province (No.2007B086),China
文摘Objective： The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods： Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed （about 15 d post wounding）. For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding. Results： Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 （p〈0.05）. Scar thickness, measured by scar elevation index （SEI） at Day 35 post wounding, was significantly reduced in the intervention group （1.09±0.19） compared with the controls （1.36±0.28）. Microvessel density （MVD） observed in the intervention group （1.73±0.94） was significantly lower than that of the control group （5.63±1.78） on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin. Conclusions： Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-dedved growth factor （PDGF） and fibroblast growth factor （FGF）, thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.
文摘Hypertrophic cardiomyopathy(HCM),the most variable cardiac disease in terms of phenotypic presentation and clinical outcome,represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance.To date,more than 1400 mutations of myofilament proteins associated with the disease have been identified,most of them "private" ones.This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations.Additionally,topics pertaining to patients' everyday lives,such as sudden cardiac death(SCD)risk stratification and prevention,along with disease prognosis,are grossly related to the genetic variation of HCM.This review incorporates contemporary research findings and addresses major aspects of HCM,including preclinical diagnosis,genetic analysis,left ventricular outflow tract obstruction and SCD.More specifically,the spectrum of genetic analysis,the selection of the best method for obstruction alleviation and the need for a unique and accuratefactor for SCD risk stratification are only some of the controversial HCM issues discussed.Additionally,future perspectives concerning HCM and myocardial ischemia,as well as atrial fibrillation,are discussed.Rather than enumerating clinical studies and guidelines,challenging problems concerning the disease are critically appraised by this review,highlighting current speculations and recommending future directions.
文摘Apical hypertrophic cardiomyopathy(AHCM) is a relatively rare morphologic variant of HCM in which the hypertrophy of myocardium is localized to the left ventricular apex. Symptoms of AHCM might vary from none to others mimic coronary artery disease including acute coronary syndrome, thus resulting in inappropriate hospitalization. Transthoracic echocardiography is the firstline imaging technique for the diagnosis of hypertrophic cardiomyopathies. However, when the hypertrophy of the myocardium is localized in the ventricular apex might results in missed diagnosis. Aim of this paper is to review the different imaging techniques used for the diagnosis of AHCM and their role in the detection and comprehension of this uncommon disease.
文摘AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy(HCM).METHODS We prospectively assessed 20 patients(mean age 53 ± 16 years,range:18-81 years,10 were male),with apical HCM. We measured global longitudinal peak systolic strain(GLPSS) in the midwall and endocardium of the left ventricle. RESULTS The diastolic thickness of the 4 apical segments was 16.25 ± 2.75 mm. All patients had a normal global systolicfunction with a fractional shortening of 50% ± 8%. In spite of supernormal left ventricular(LV) systolic function,midwall GLPSS was decreased in all patients,more in the apical(-7.3% ±-8.8%) than in basal segments(-15.5% ±-6.93%),while endocardial GLPPS was significantly greater and reached normal values(apical:-22.8% ±-7.8%,basal:-17.9% ±-7.5%). CONCLUSION This study shows that two-dimensional strain was decreased mainly confined to the mesocardium,while endocardium myocardial deformation was preserved in HCM and allowed to identify subclinical LV dysfunction. This transmural heterogeneity in systolic strain had not been previously described in HCM and could be explained by the distribution of myofibrillar disarray in deep myocardial areas. The clinical application of this novel finding may help further understanding of the pathophysiology of HCM.
