The journal of cardiovascular aging最新文献

{"title":"COVID-19 and BRD4: a stormy and cardiotoxic bromo-romance.","authors":"Emma L Robinson, Timothy A McKinsey","doi":"10.20517/jca.2021.20","DOIUrl":"10.20517/jca.2021.20","url":null,"abstract":"<p><p>Severe systemic inflammation in COVID-19 patients can lead to dysfunction of multiple organs, including the heart. Using an ex vivo cardiac organoid system, Mills et al discovered that inhibitors of the chromatin reader protein, bromodomain-containing protein 4, protect cardiomyocytes from COVID-associated \"cytokine storm\". We briefly review these important findings and highlight the translational significance of the work.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39583644","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":"Transient reprogramming primes the heart for repair.","authors":"Natalie A Gude,&nbsp;Fareheh Firouzi,&nbsp;Mark A Sussman","doi":"10.20517/jca.2021.31","DOIUrl":"https://doi.org/10.20517/jca.2021.31","url":null,"abstract":"Graphical Abstract","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39583645","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":"Metabolic targets in cardiac aging and rejuvenation","authors":"Chang Liu, Xiao Zhang, Meiyu Hu, Yi Lu, P. Gokulnath, Gururaja Vulugundam, Junjie Xiao","doi":"10.20517/jca.2022.31","DOIUrl":"https://doi.org/10.20517/jca.2022.31","url":null,"abstract":"Cardiac aging is accompanied by progressive loss of cellular function, leading to impaired heart function and heart failure. There is an urgent need for efficient strategies to combat this age-related cardiac dysfunction. A growing number of events suggest that age-related cardiac diseases are tightly related to metabolic imbalance. This review summarizes recent findings concerning metabolic changes during cardiac aging and highlights the therapeutic approaches that target metabolic pathways in cardiac aging.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657204","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":"Associations between estimated and measured carotid-femoral pulse wave velocity in older Black and White adults: the atherosclerosis risk in communities (ARIC) study.","authors":"Kevin Heffernan, Lee Stoner, Michelle L Meyer, Adam Keifer, Lauren Bates, Patricia Pagan Lassalle, Erik D Hanson, Masahiro Horiuchi, Erin D Michos, Anna Kucharska-Newton, Kunihiro Matsushita, Timothy M Hughes, Hirofumi Tanaka","doi":"10.20517/jca.2021.22","DOIUrl":"10.20517/jca.2021.22","url":null,"abstract":"<p><strong>Introduction: </strong>Aortic stiffness offers important insight into vascular aging and cardiovascular disease (CVD) risk. The referent measure of aortic stiffness is carotid-femoral pulse wave velocity (cfPWV). cfPWV can be estimated (ePWV) from age and mean arterial pressure. Few studies have directly compared the association of ePWV to measured cfPWV, particularly in non-White adults. Moreover, whether ePWV and cfPWV correlate similarly with CVD risk remains unexplored.</p><p><strong>Aim: </strong>(1) To estimate the strength of the agreement between ePWV and cfPWV in both Black and White older adults; and (2) to compare the associations of ePWV and cfPWV with CVD risk factors and determine whether these associations were consistent across races.</p><p><strong>Methods and results: </strong>We evaluated 4478 [75.2 (SD 5.0) years] Black and White older adults in the Atherosclerosis Risk in Communities (ARIC) Study. cfPWV was measured using an automated pulse waveform analyzer. ePWV was derived from an equation based on age and mean arterial pressure. Association and agreement between the two measurements were determined using Pearson's correlation coefficient (<i>r</i>), standard error of estimate (SEE), and Bland-Altman analysis. Associations between traditional risk factors with ePWV and cfPWV were evaluated using linear mixed regression models. We observed weak correlations between ePWV and cfPWV within White adults (<i>r</i> = 0.36) and Black adults (<i>r</i> = 0.31). The mean bias for Bland-Altman analysis was low at -0.17 m/s (95%CI: -0.25 to -0.09). However, the inspection of the Bland-Altman plots indicated systematic bias (<i>P</i> < 0.001), which was consistent across race strata. The SEE, or typical absolute error, was 2.8 m/s suggesting high variability across measures. In models adjusted for sex, prevalent diabetes, the number of prevalent cardiovascular diseases, and medication count, both cfPWV and ePWV were positively associated with heart rate, triglycerides, and fasting glucose, and negatively associated with body mass index (BMI) and smoking status in White adults (<i>P</i> < 0.05). cfPWV and ePWV were not associated with heart rate, triglycerides, and fasting glucose in Black adults, while both measures were negatively associated with BMI in Black adults.</p><p><strong>Conclusions: </strong>Findings suggest a weak association between ePWV and cfPWV in older White and Black adults from ARIC. There were similar weak associations between CVD risk factors with ePWV and cfPWV in White adults with subtle differences in associations in Black adults.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9190637","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":"Systemic delivery of large-scale manufactured Wharton's Jelly mesenchymal stem cell-derived extracellular vesicles improves cardiac function after myocardial infarction.","authors":"Michael A Bellio,&nbsp;Rosemeire M Kanashiro-Takeuchi,&nbsp;Lauro Takeuchi,&nbsp;Shathiyah Kulandavelu,&nbsp;Yee-Shuan Lee,&nbsp;Wayne Balkan,&nbsp;Karen C Young,&nbsp;Joshua M Hare,&nbsp;Aisha Khan","doi":"10.20517/jca.2021.21","DOIUrl":"https://doi.org/10.20517/jca.2021.21","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiovascular disease and myocardial infarction are leading causes of morbidity and mortality in aged populations. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are under evaluation as a therapeutic option for the treatment of myocardial infarction.</p><p><strong>Aim: </strong>This study aimed to develop a large-scale manufacturing procedure to harvest clinical-grade EVs required for the translation of EVs to the clinic.</p><p><strong>Methods and results: </strong>We compared the efficiency of large scale MSC-derived EV production and characterized EV miRNA cargo using the Quantum bioreactor with either fetal bovine serum or human platelet lysate (PLT)-containing expansion media. We tested the potency of the EV products in a murine model of acute myocardial infarction. Our results demonstrate an advantage of the Quantum bioreactor as a large-scale platform for EV production using PLT media; however, both media produced EVs with similar effects <i>in vivo.</i> The systemic delivery of EV products improved cardiac function following myocardial infarctions as indicated by a significant improvement in ejection fraction as well as parameters of cardiac performance, afterload, contractility and lusitropy.</p><p><strong>Conclusion: </strong>These findings have important implications for scale-up strategies of EVs and will facilitate clinical trials for their clinical evaluation.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39883093","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":"New insights into the dynamics of age-related clonal hematopoiesis","authors":"M. Zuriaga, J. Fuster","doi":"10.20517/jca.2022.38","DOIUrl":"https://doi.org/10.20517/jca.2022.38","url":null,"abstract":"© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657262","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":"Find Your Ikigai in Science","authors":"L. Rouhi","doi":"10.20517/jca.2022.04","DOIUrl":"https://doi.org/10.20517/jca.2022.04","url":null,"abstract":"","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657528","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":"Boosting circadian autophagy by means of intermittent time-restricted feeding: a novel anti-ageing strategy?","authors":"Sebastiano Sciarretta,&nbsp;Maurizio Forte,&nbsp;Junichi Sadoshima","doi":"10.20517/jca.2021.33","DOIUrl":"https://doi.org/10.20517/jca.2021.33","url":null,"abstract":"© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10459288","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":"Taking in the trash: bioreactors for the mass production of clinical-grade extracellular vesicles","authors":"Matthew J. Robeson, Michael E. Davis","doi":"10.20517/jca.2021.32","DOIUrl":"https://doi.org/10.20517/jca.2021.32","url":null,"abstract":"© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657468","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":"Mutant SRF and YAP synthetic modified mRNAs drive cardiomyocyte nuclear replication","authors":"Siyu C. Xiao, Rui Liang, Azeez B. Muili, Xuanye Cao, S. Navran, R. Schwartz, Dinakar Iyer","doi":"10.20517/jca.2022.17","DOIUrl":"https://doi.org/10.20517/jca.2022.17","url":null,"abstract":"Introduction: Aging is associated with sarcopenia, myocyte loss, and dysfunction. The problem is compounded as the adult heart lacks the regenerative capacity to self-repair. Serum response factor’s (SRF’s) dual activity is essential for cell replication and heart cell differentiation. SRF interacts with cofactors, such as NKX2-5 and GATA4, which give cardiac-specific gene activity, and ETS factors such as ELK1 drive cell replication. Recently, the mutant YAP-5SA of the Hippo pathway was implicated in cardiomyocyte proliferation and growth. Aim: We hypothesized that disruption of interactions of SRF with NKX2-5 and GATA4 would lead to dedifferentiation of cardiomyocytes to a proliferative stem cell state and complement YAP-5SA to generate undifferentiated cardiomyocytes in a more primitive replicative state. Methods and results: To weaken SRF interactions with NKX2-5 and GATA4, alanine scanning mutations were generated across the SRF N-terminus of the MADS-box. One SRF mutant, SRF153(A3), was tested along with the YAP-5SA mutant, as degradable synthetic modified mRNAs (mmRNAs), in rat primary cardiomyocytes. To measure cell replication, adult cardiomyocytes were pulsed with alpha-EdU and then DAPI stained, while gene activity was assayed by RNA sequencing. To measure chromatin remodeling, Transposon 5 was used in ATAC sequencing. We observed that single and triple alanine substitutions of mutants centering over SRF-Lys154 essentially blocked myocyte differentiation, and NKX2-5 and GATA4 failed to stabilize mutated SRF DNA binding. Instead, many stem cell factors including NANOG and OCT4 were induced. SRF153(A3) does not recognize SRF response elements per ATAC sequencing and consequently induces stem cell factors such as NANOG and OCT4, cardiomyocyte dedifferentiation, and cell cycle reentry. SRF153(A3) and YAP5SA mmRNA led to alpha-EDU incorporation in ~35% of the cardiomyocytes. DIAPH 3, a marker of the contractile ring during anaphase, appeared between and around replicated nuclei in three-month-old adult mouse cardiac myocytes. The combination of these synthetic mRNA increased nuclei replication with the expression of origin of replication genes, while genes associated with cardiomyocyte differentiation were down-regulated. ATAC sequencing revealed SRF153(A3) and YAP5SA mmRNA-induced chromatin remodeling of cell cycle, spindle, and growth factor genes by additive and synergistic activities. Conclusion: SRF153(A3) synthetic mmRNA and the mutant YAP-5SA mmRNA induced cardiomyocyte dedifferentiation, to nuclear replication in adult cardiac myocytes. The combinatorial use of mmRNA encoding SRF153(A3) and YAP-5SA has the potential to become a powerful clinical strategy for treating human heart disease.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657093","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}