The journal of cardiovascular aging最新文献

{"title":"Adipose tissue lymphocytes and obesity.","authors":"Feng Gao, Benjamin Litchfield, Huaizhu Wu","doi":"10.20517/jca.2023.38","DOIUrl":"10.20517/jca.2023.38","url":null,"abstract":"<p><p>Obesity is associated with chronic inflammation in adipose tissue (AT), mainly evidenced by infiltration and phenotypic changes of various types of immune cells. Macrophages are the major innate immune cells and represent the predominant immune cell population within AT. Lymphocytes, including T cells and B cells, are adaptive immune cells and constitute another important immune cell population in AT. In obesity, CD8+ effector memory T cells, CD4+ Th1 cells, and B2 cells are increased in AT and promote AT inflammation, while regulatory T cells and Th2 cells, which usually function as immune regulatory or type 2 inflammatory cells, are reduced in AT. Immune cells may regulate the metabolism of adipocytes and other cells through various mechanisms, contributing to the development of metabolic diseases, including insulin resistance and type 2 diabetes. Efforts targeting immune cells and inflammation to prevent and treat obesity-linked metabolic disease have been explored, but have not yielded significant success in clinical studies. This review provides a concise overview of the changes in lymphocyte populations within AT and their potential role in AT inflammation and the regulation of metabolic functions in the context of obesity.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061510","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":"Fueling cardiac myocyte proliferation","authors":"Manisha Deogharia, Priyatansh Gurha","doi":"10.20517/jca.2023.47","DOIUrl":"https://doi.org/10.20517/jca.2023.47","url":null,"abstract":"","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"49 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139125220","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":"Nobiletin, a polymethoxylated flavonoid, regulates cell survival via the nuclear receptor RORα in cardiomyocytes","authors":"Yuka Shiheido-Watanabe, J. Sadoshima","doi":"10.20517/jca.2023.46","DOIUrl":"https://doi.org/10.20517/jca.2023.46","url":null,"abstract":"","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"18 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139129877","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":"Molecular mechanisms underlying sarcopenia in heart failure","authors":"Cody A. Rutledge","doi":"10.20517/jca.2023.40","DOIUrl":"https://doi.org/10.20517/jca.2023.40","url":null,"abstract":"The loss of skeletal muscle, also known as sarcopenia, is an aging-associated muscle disorder that is disproportionately present in heart failure (HF) patients. HF patients with sarcopenia have poor outcomes compared to the overall HF patient population. The prevalence of sarcopenia in HF is only expected to grow as the global population ages, and novel treatment strategies are needed to improve outcomes in this cohort. Multiple mechanistic pathways have emerged that may explain the increased prevalence of sarcopenia in the HF population, and a better understanding of these pathways may lead to the development of therapies to prevent muscle loss. This review article aims to explore the molecular mechanisms linking sarcopenia and HF, and to discuss treatment strategies aimed at addressing such molecular signals.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"190 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139637992","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":"Hypoxia-induced stabilization of HIF2A promotes cardiomyocyte proliferation by attenuating DNA damage.","authors":"Shah R Ali, Ngoc Uyen Nhi Nguyen, Ivan Menendez-Montes, Ching-Cheng Hsu, Waleed Elhelaly, Nicholas T Lam, Shujuan Li, Abdallah Elnwasany, Yuji Nakada, Suwannee Thet, Roger S Y Foo, Hesham A Sadek","doi":"10.20517/jca.2023.43","DOIUrl":"10.20517/jca.2023.43","url":null,"abstract":"<p><strong>Introduction: </strong>Gradual exposure to a chronic hypoxic environment leads to cardiomyocyte proliferation and improved cardiac function in mouse models through a reduction in oxidative DNA damage. However, the upstream transcriptional events that link chronic hypoxia to DNA damage have remained obscure.</p><p><strong>Aim: </strong>We sought to determine whether hypoxia signaling mediated by the hypoxia-inducible factor 1 or 2 (HIF1A or HIF2A) underlies the proliferation phenotype that is induced by chronic hypoxia.</p><p><strong>Methods and results: </strong>We used genetic loss-of-function models using cardiomyocyte-specific HIF1A and HIF2A gene deletions in chronic hypoxia. We additionally characterized a cardiomyocyte-specific HIF2A overexpression mouse model in normoxia during aging and upon injury. We performed transcriptional profiling with RNA-sequencing on cardiac tissue, from which we verified candidates at the protein level. We find that HIF2A - rather than HIF1A - mediates hypoxia-induced cardiomyocyte proliferation. Ectopic, oxygen-insensitive HIF2A expression in cardiomyocytes reveals the cell-autonomous role of HIF2A in cardiomyocyte proliferation. HIF2A overexpression in cardiomyocytes elicits cardiac regeneration and improvement in systolic function after myocardial infarction in adult mice. RNA-sequencing reveals that ectopic HIF2A expression attenuates DNA damage pathways, which was confirmed with immunoblot and immunofluorescence.</p><p><strong>Conclusion: </strong>Our study provides mechanistic insights about a new approach to induce cardiomyocyte renewal and mitigate cardiac injury in the adult mammalian heart. In light of evidence that DNA damage accrues in cardiomyocytes with aging, these findings may help to usher in a new therapeutic approach to overcome such age-related changes and achieve regeneration.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061762","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":"Arriving on time: decoding macrophage involvement in atrial fibrillation.","authors":"Yue Yuan,&nbsp;Na Li","doi":"10.20517/jca.2023.28","DOIUrl":"10.20517/jca.2023.28","url":null,"abstract":"Atrial fibrillation (AF) is the most common arrhythmia in adults, with a rising incidence and prevalence [1] . It is associated with increased risks of stroke, heart failure, and death. The risk of AF is associated with various factors, including aging, structural heart disease, obesity, hypertension, inflammation, and others. Rhythm control and rate control are the primary strategies for managing AF in clinical practice. While the focus of rate control is to slow down the heart rate without necessarily converting the abnormal rhythm to normal sinus rhythm, the more desirable rhythm control is to restore and maintain the normal sinus rhythm by utilizing cardioversion, antiarrhythmic drugs, or catheter ablation. The catheter-based ablation techniques have significantly progressed over the past several decades and generally yield satisfactory immediate results, yet the recurrence of AF remains a persistent challenge. Understanding the mechanisms that lead to AF is crucial for developing novel therapeutic strategies.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10287496","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":"Fibroblasts, myofibroblasts and cardiac arrhythmias","authors":"Nikolaos G. Frangogiannis","doi":"10.20517/jca.2023.37","DOIUrl":"https://doi.org/10.20517/jca.2023.37","url":null,"abstract":"","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135112697","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":"GDF11 and aging biology - controversies resolved and pending","authors":"Laura Ben Driss, John Lian, Ryan G. Walker, James A. Howard, Thomas B. Thompson, Lee L. Rubin, Amy J. Wagers, Richard T. Lee","doi":"10.20517/jca.2023.23","DOIUrl":"https://doi.org/10.20517/jca.2023.23","url":null,"abstract":"Since the exogenous administration of GDF11, a TGF-ß superfamily member, was reported to have beneficial effects in some models of human disease, there have been many research studies in GDF11 biology. However, many studies have now confirmed that exogenous administration of GDF11 can improve physiology in disease models, including cardiac fibrosis, experimental stroke, and disordered metabolism. GDF11 is similar to GDF8 (also called Myostatin), differing only by 11 amino acids in their mature signaling domains. These two proteins are now known to be biochemically different both in vitro and in vivo . GDF11 is much more potent than GDF8 and induces more strongly SMAD2 phosphorylation in the myocardium compared to GDF8. GDF8 and GDF11 prodomain are only 52% identical and are cleaved by different Tolloid proteases to liberate the mature signaling domain from inhibition of the prodomain. Here, we review the state of GDF11 biology, highlighting both resolved and remaining controversies.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135667171","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":"mt-tRNAs in the polymerase gamma mutant heart","authors":"M. Bilal Bayazit, Ashley Francois, Erin McGrail, Federica Accornero, Matthew S. Stratton","doi":"10.20517/jca.2023.26","DOIUrl":"https://doi.org/10.20517/jca.2023.26","url":null,"abstract":"Introduction: Mice harboring a D257A mutation in the proofreading domain of the mitochondrial DNA polymerase, Polymerase Gamma (POLG), experience severe metabolic dysfunction and display hallmarks of accelerated aging. We previously reported a mitochondrial unfolded protein response (UPTmt) - like (UPRmt-like) gene and protein expression pattern in the right ventricular tissue of POLG mutant mice. Aim: We sought to determine if POLG mutation altered the expression of genes encoded by the mitochondria in a way that might also reduce proteotoxic stress. Methods and Results: The expression of genes encoded by the mitochondrial DNA was interrogated via RNA-seq and northern blot analysis. A striking, location-dependent effect was seen in the expression of mitochondrial-encoded tRNAs in the POLG mutant as assayed by RNA-seq. These expression changes were negatively correlated with the tRNA partner amino acid’s amyloidogenic potential. Direct measurement by northern blot was conducted on candidate mt-tRNAs identified from the RNA-seq. This analysis confirmed reduced expression of MT-TY in the POLG mutant but failed to show increased expression of MT-TP, which was dramatically increased in the RNA-seq data. Conclusion: We conclude that reduced expression of amyloid-associated mt-tRNAs is another indication of adaptive response to severe mitochondrial dysfunction in the POLG mutant. Incongruence between RNA-seq and northern blot measurement of MT-TP expression points towards the existence of mt-tRNA post-transcriptional modification regulation in the POLG mutant that alters either polyA capture or cDNA synthesis in RNA-seq library generation. Together, these data suggest that 1) evolution has distributed mt-tRNAs across the circular mitochondrial genome to allow chromosomal location-dependent mt-tRNA regulation (either by expression or PTM) and 2) this regulation is cognizant of the tRNA partner amino acid’s amyloidogenic properties.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"80 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135884211","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":"Retinoic acid-related orphan receptors regulate autophagy and cell survival in cardiac myocytes during hypoxic stress","authors":"Eryn Kirshenbaum, Huong Nguyen, Victoria Margulets, Molly Crandall, Darya Nematisouldaragh, Inna Rabinovich-Nikitin","doi":"10.20517/jca.2023.31","DOIUrl":"https://doi.org/10.20517/jca.2023.31","url":null,"abstract":"Introduction: Autophagy is a highly conserved evolutionary process that regulates cell quality control through protein degradation, organelle turnover, and recycling of cellular components by fusing with lysosomes. Defects in autophagy can lead to increased reactive oxygen species (ROS) and oxidative stress from impaired mitochondrial clearance by mitophagy. These defects are commonly associated with chronic human diseases such as cancer, myocardial infarction, neurodegenerative diseases, and aging. Aim: Herein, we show that the gene Retinoic Acid-Related Orphan Receptors α (Rora ) is cardioprotective through modulation of autophagy and clearance of damaged ROS-producing mitochondria in cardiac myocytes. Methods and results: We show that RORα is downregulated during hypoxia, leading to increased death of cardiac cells and enhanced mitochondrial perturbations. We demonstrate that the small molecule Nobiletin, a polymethoxy flavonoid, can induce RORα activation and downregulate the aging-associated marker p16, coincident with reduced ROS-producing mitochondria. We further show that Nobiletin binds directly to the Rora gene promoter, leading to activation of autophagic function and increased cell survival of cardiac myocytes during hypoxia. Interestingly, loss of RORα activity during hypoxia resulted in the failure of Nobiletin to rescue autophagy and inhibits its capacity for cardiac protection. Furthermore, the inactivation of autophagy by ATG7 knockdown abrogated the cytoprotective effects of Nobiletin on autophagic activation. Conclusion: Collectively, these results demonstrate that RORα regulates autophagic processes linked to aging upon activation with Nobiletin. Interventions that activate RORα may prove beneficial in reducing hypoxia-induced mitochondrial ROS associated with cardiac aging.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135992785","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}