The journal of cardiovascular aging最新文献

{"title":"Thrombosis and myocardial infarction: the role of bioresorbable scaffolds.","authors":"Massoud A Leesar,&nbsp;Marc D Feldman","doi":"10.20517/jca.2022.41","DOIUrl":"https://doi.org/10.20517/jca.2022.41","url":null,"abstract":"<p><p>Coronary stents have dramatically improved the treatment of coronary artery stenosis. In-stent-restenosis (ISR) and stent thrombosis (ST) pose major obstacles to the success of coronary stenting. Drug-eluting stents (DES) emerged as a major breakthrough in stenting and significantly reduced ISR. Despite taking dual antiplatelet therapy (DAPT), very late ST has remained a major obstacle in the success of DES. This occurs regardless of the type of polymer or antiproliferative agent in the contemporary stents. Such adverse events occur at a rate of approximately 2% to 3% per year after first year, which have been attributed to the strut fractures, loss of vessel compliance and vasomotion, and neoatherosclerosis. Fully bioresorbable scaffolds (BRS) have emerged in an effort to overcome these limitations leading to a \"leave nothing behind\" approach. While appealing, the initial experience with BRS technology was hampered by increased rates of BRS thrombosis compared with DES. In this review, we summarized underlying mechanisms leading to BRS failure and provided insights into optimizing BRS deployment with intravascular imaging. In addition, we outlined the perspectives of new generations BRS with thinner struts and new designs as well as alternative materials to improve outcome.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10288217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10102879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid overload - a culprit for hypertrophic cardiomyopathy?","authors":"Lilei Zhang,&nbsp;Na Li","doi":"10.20517/jca.2022.43","DOIUrl":"https://doi.org/10.20517/jca.2022.43","url":null,"abstract":"Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy in the absence of loading conditions such as hypertension or valvular diseases. It is the most common cause of inherited cardiac diseases, with a prevalence of 1 in 500 worldwide [1] . It is also the most common cause of sudden death in the young [2] . While etiology is heterogenous, at least half of the HCMs with a molecular diagnosis were due to pathogenic or likely pathogenic variants in sarcomere protein encoding genes, predominantly MYH7 (encoding beta-myosin heavy chain) and MYBPC3 (encoding cardiac myosin binding protein C) [2] . While the pathophysiology of HCM has been heavily debated, the most recent studies converge on the hypercontractility hypothesis [3] . Contractile protein mutations that cause either increased contractility or impaired relaxation can result in HCM. The main mechanisms that have been proposed are associated with increased calcium sensitivity, increased myosin head ATPase activity, or reduced myosin super-relaxed state among others. This hypothesis has been well supported by studies utilizing the disease-modeling murine models carrying human pathogenic variants or the patient-derived human induced pluripotent stem cell differentiated cardiomyocytes models [4] . The concentric hypertrophy associated with HCM has been attributed to increased calcium induced calcineurin signaling and activation of mitogen-activated protein kinase kinase 1-extracellular signal-regulated kinase 1/2 (MEK1-ERK1/2) signaling pathways [5","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9363658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What ails the NIH peer review study sections and how to fix the review process of the grant applications.","authors":"Ali J Marian","doi":"10.20517/jca.2023.3","DOIUrl":"https://doi.org/10.20517/jca.2023.3","url":null,"abstract":"The concern has been on my mind for a while, but I had procrastinated putting it down on paper till now. It was the recent announcement by the National Institutes of Health (NIH) Center for Scientific Review on the proposed changes to the review criteria of the grant applications submitted to the NIH study sections that provided the impetus to write this opinion article. The Christmas holidays provided the time needed to write it. Accordingly, “NIH proposes to reorganize the (current) five review criteria into three factors” as follows:","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10763443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PANoptosis is a prominent feature of desmoplakin cardiomyopathy.","authors":"Melis Olcum,&nbsp;Leila Rouhi,&nbsp;Siyang Fan,&nbsp;Maya M Gonzales,&nbsp;Hyun-Hwan Jeong,&nbsp;Zhongming Zhao,&nbsp;Priyatansh Gurha,&nbsp;Ali J Marian","doi":"10.20517/jca.2022.34","DOIUrl":"https://doi.org/10.20517/jca.2022.34","url":null,"abstract":"<p><strong>Introduction: </strong>Arrhythmogenic cardiomyopathy (ACM) is hereditary cardiomyopathy caused by pathogenic variants (mutations) in genes encoding the intercalated disc (ID), particularly desmosome proteins. ACM caused by mutations in the <i>DSP</i> gene encoding desmoplakin (DSP) is characterized by the prominence of cell death, myocardial fibrosis, and inflammation, and is referred to as desmoplakin cardiomyopathy.</p><p><strong>Aim: </strong>The aim of this article was to gain insight into the pathogenesis of DSP cardiomyopathy.</p><p><strong>Methods and results: </strong>The <i>Dsp</i> gene was exclusively deleted in cardiac myocytes using tamoxifen-inducible MerCreMer (<i>Myh6-Mcm</i> ^Tam) and floxed <i>Dsp</i> (<i>Dsp</i> ^F/F) mice (<i>Myh6-Mcm</i> ^Tam:<i>Dsp</i> ^F/F). Recombination was induced upon subcutaneous injection of tamoxifen (30 mg/kg/d) for 5 days starting post-natal day 14. Survival was analyzed by Kaplan-Meier plots, cardiac function by echocardiography, arrhythmias by rhythm monitoring, and gene expression by RNA-Seq, immunoblotting, and immunofluorescence techniques. Cell death was analyzed by the TUNEL assay and the expression levels of specific markers were by RT-PCR and immunoblotting. Myocardial fibrosis was assessed by picrosirius red staining of the myocardial sections, RT-PCR, and immunoblotting. The <i>Myh6-Mcm</i> ^Tam: <i>Dsp</i> ^F/F mice showed extensive molecular remodeling of the IDs and the differential expression of ~10,000 genes, which predicted activation of KDM5A, IRFs, and NFκB and suppression of PPARGC1A and RB1, among others in the DSP-deficient myocytes. Gene set enrichment analysis predicted activation of the TNFα/NFκB pathway, inflammation, cell death programs, and fibrosis. Analysis of cell death markers indicated PANoptosis, comprised of apoptosis (increased CASP3, CASP8, BAD and reduced BCL2), necroptosis (increased RIPK1, RIPK3, and MLKL), and pyroptosis (increased GSDMD and ASC or PYCARD) in the DSP-deficient myocytes. Transcript levels of the pro-inflammatory and pro-fibrotic genes were increased and myocardial fibrosis comprised ~25% of the myocardium in the DSP-deficient hearts. The <i>Myh6-Mcm</i> ^Tam:<i>Dsp</i> ^F/F mice showed severe cardiac systolic dysfunction and ventricular arrhythmias, and died prematurely with a median survival rate of ~2 months.</p><p><strong>Conclusion: </strong>The findings identify PANoptosis as a prominent phenotypic feature of DSP cardiomyopathy and set the stage for delineating the specific molecular mechanisms involved in its pathogenesis. The model also provides the opportunity to test the effects of pharmacological and genetic interventions on myocardial fibrosis and cell death.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9473096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parsing cell death in arrhythmogenic cardiomyopathy: PANoptosis.","authors":"Calum A MacRae","doi":"10.20517/jca.2022.45","DOIUrl":"https://doi.org/10.20517/jca.2022.45","url":null,"abstract":"There are many ways for a cell to die and each of the modes of cell death has been subject to intense evolutionary selection pressure[1]. Discrete survival pathways and related programmed cell death (PCD) pathways have emerged in single cells, across communities of cells, and in all multicellular organisms. Many of the factors which trigger programmed cell death act through perturbations in homeostatic parameters such as osmotic pressure, mechanical force, temperature, oxygen tension, pH, transmembrane potential, DNA damage or metabolic substrate availability. Although they use distinctive sensor systems and signaling pathways, microbial or other injuries and their responses can often be understood using these same rubrics and the survival of whole organs and organisms can be framed through community behaviors that typically integrate heterogeneous responses to single insults across different cells or cell types[2].","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10162710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9799986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare variants in the FBN1 gene are associated with sporadic dilated cardiomyopathy in a Chinese Han population","authors":"Dong-Qing Wu, Yang Sun, Chenze Li, Lei Xiao, Jiaqi Dai, Yanghui Chen, Peng Chen, Hong Wang, Bo Yu, Haoran Wei, Rui Li, Xiuli Song, Ting Yu, Leming Shi, D. Wang","doi":"10.20517/jca.2023.12","DOIUrl":"https://doi.org/10.20517/jca.2023.12","url":null,"abstract":"Introduction: Dilated cardiomyopathy (DCM) represents a diverse set of myocardial diseases characterized by notable genetic heterogeneity. Although over 50 genes have been associated with DCM, these collectively explain 35% of idiopathic DCM cases. Variants in the FBN1 gene encoding fibrillin-1 are primarily linked to connective tissue disorders. Considering the potential of these disorders to impact myocardial tissue, this study probes into the possible association between FBN1 variants and DCM. Aim: The objective of this study was to investigate the association between FBN1 variants and DCM in a Chinese Han population. Methods and Results: We performed whole-exome sequencing (WES) to identify rare FBN1 variants among 1,059 DCM cases and 514 controls. Utilizing a case-control strategy and the optimal sequence kernel association test (SKAT-O), we found a significant enrichment of rare deleterious FBN1 variants in DCM patients (19 of 1,059 vs. 0 of 514, PSKAT-O = 7.49E-04). Clinical characteristics analysis indicated a higher occurrence of atrial fibrillation and a higher rate of implantable cardioverter-defibrillator (ICD) implantation among DCM patients carrying FBN1 variants (FBN1+) compared to non-carriers (FBN1-). However, these FBN1 variants did not significantly affect primary endpoints, defined as cardiac mortality or heart transplantation, yet appeared to increase the risk of secondary endpoints, including all-cause mortality or heart failure recurrence. Conclusion: The findings suggest an association between rare deleterious variants in the FBN1 gene and DCM in a Chinese Han population. Our findings underline the importance of further research to validate these results and elucidate the role of FBN1 in DCM. Potential Impact of the findings: This research provides fresh insights into the potential role of FBN1 rare variants in DCM, pointing to new directions for future genetic studies and potential therapeutic strategies in DCM management.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Passion for science: a journey of inspiration and dedication","authors":"L. Rouhi","doi":"10.20517/jca.2023.21","DOIUrl":"https://doi.org/10.20517/jca.2023.21","url":null,"abstract":"","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of paracrine crosstalk between myeloid and endothelial cells in myocardial angiogenesis and infarcted heart repair.","authors":"Kyu-Won Cho,&nbsp;Seongho Bae,&nbsp;Young-Sup Yoon","doi":"10.20517/jca.2022.37","DOIUrl":"https://doi.org/10.20517/jca.2022.37","url":null,"abstract":"Ischemic heart disease is one of the leading causes of morbidity and mortality in the USA. It is mainly caused by the narrowing or occlusion of coronary arteries by plaque buildup, leading to a limited supply of oxygen and nutrients to the cardiac muscle. This results in necrotic death of cardiomyocytes (CMs). CM necrosis leads to the production of cytokines, chemokines, and damage-associated molecular patterns (DAMPs), which recruit immune cells from the bone marrow (BM) [1] . Infiltrated immune cells secrete proteases and cytokines that mediate inflammatory responses and fibroblast activation [1] . Subsequently, the damaged cardiac muscle is replaced with extracellular matrix produced by activated fibroblasts, leading to myocardial remodeling and dysfunction. Attempts to restore blood vessels (a.k.a. therapeutic angiogenesis) reduced fibrosis and improved the performance of the infarcted heart [2] . A possible underlying mechanism is that the supply of oxygen and nutrients via new blood vessels would preserve CM survival and support the health and function of remaining cardiovascular cells, thereby preventing adverse cardiac remodeling. Thus, therapeutic angiogenesis has been considered one of the important therapeutic approaches for ischemic heart diseases. Investigations","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10464960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune mechanisms of cardiac aging.","authors":"Daniel R Goldstein, Ahmed Abdel-Latif","doi":"10.20517/jca.2023.02","DOIUrl":"10.20517/jca.2023.02","url":null,"abstract":"<p><p>Advances in healthcare and improvements in living conditions have led to rising life expectancy worldwide. Aging is associated with excessive oxidative stress, a chronic inflammatory state, and limited tissue healing, all of which result in an increased risk of heart failure. In fact, the prevalence of heart failure approaches 40% in the ninth decade of life, with the majority of these cases suffering from heart failure with preserved ejection fraction (HFpEF). In cardiomyocytes (CMs), age-related mitochondrial dysfunction results in disrupted calcium signaling and covalent protein-linked aggregates, which cause cardiomyocyte functional disturbances, resulting in increased stiffness and diastolic dysfunction. Importantly, aging is also associated with chronic low-grade, sterile inflammation, which alters the function of interstitial cardiac cells and leads to cardiac fibrosis. Taken together, cardiac aging is associated with cellular, structural, and functional changes in the heart that contribute to the rising prevalence of heart failure in older people.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9742667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mTOR signaling pathway in cardiac aging.","authors":"Dao-Fu Dai,&nbsp;Ping Kang,&nbsp;Hua Bai","doi":"10.20517/jca.2023.10","DOIUrl":"https://doi.org/10.20517/jca.2023.10","url":null,"abstract":"<p><p>The mammalian target of rapamycin (mTOR) is one of the most important signaling pathways that regulate nutrient sensing, cell growth, metabolism, and aging. The mTOR pathway, particularly mTOR complex 1 (mTORC1), has been shown to control aging, lifespan, and healthspan through the regulation of protein synthesis, autophagy, mitochondrial function, and metabolic health. The mTOR pathway also plays critical roles in the heart, from cardiac development, growth and maturation, and maintenance of cardiac homeostasis. Hyperactivation of mTORC1 signaling is well documented in aging and many age-related pathologies, including age-related cardiac dysfunction and heart failure. Suppression of mTORC1 by calorie restriction or rapamycin not only extends lifespan but also restores youthful phenotypes in the heart. In this article, we review model organisms of cardiac aging and highlight recent advances in the impact of the mTORC1 pathway on organismal and cardiac aging, particularly in <i>Drosophila</i> and mice. We focus on the downstream signaling pathways S6 kinase and 4EBP1, which regulates protein synthesis, as well as ULK1 and its related pathway that regulates autophagy. The interaction with mTOR complex 2 (mTORC2) and its potential role in cardiac aging are also discussed.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10237620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9939349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}