The journal of cardiovascular aging最新文献

{"title":"The TNNI3 p.R186Q mutation is responsible for hypertrophic cardiomyopathy via promoting FASN-stimulated abnormal fatty acid metabolism","authors":"Linjuan Guo, Yuhao Su, Chen Chen, Qiongqiong Zhou, Yang Shen, Zhenhong Jiang, Xia Yan, Xiaoqing Li, Wen Zhuo, Xiaogang Peng, R. Wan, K. Hong","doi":"10.20517/jca.2022.29","DOIUrl":"https://doi.org/10.20517/jca.2022.29","url":null,"abstract":"Introduction: The TNNI3 gene encodes the protein of cardiac troponin I (cTnI), which is an inhibitory subunit of sarcomeres. Mutations in this gene account for 3% of hypertrophic cardiomyopathy (HCM) and the molecular mechanism is complex. Recently, lipid metabolism has been revealed to be involved in HCM. Aim: The purpose of this work is to identify whether the pathological mechanism of the hotspot mutation TNNI3 p.R186Q in HCM is related to abnormal lipid metabolism. Methods and Results: A knock-in (KI) mouse model carrying the Tnni3 p.R186Q homozygous mutation (Tnni3R186Q/R186Q) was novelty generated by CRISPR/Cas9 technology and successfully constructed a typical phenotype of cardiac-myopathy. Likewise, neonatal rat cardiomyocytes (NRCMs) transfected with a mutant plasmid with the TNNI3 p.R186Q mutation showed the same phenomenon. In-depth experiments on related functions and molecular mechanisms were conducted, and Tnni3R186Q/R186Q mice exhibited abnormal fatty acid metabolism, which was induced by the activation of epidermal growth factor receptor (EGFR)-dependent high expression of fatty acid synthase (FASN) in vivo and in vitro. Specifically, the direct binding of EGFR and cTnI was destroyed by TNNI3 p.R186Q mutation, as observed through bioinformatics, Co-IP and GST-pull down analysis. Conclusion: In the present study, we successfully engineered Tnni3R186Q/R186Q mice with the typical phenotype of myocardial hypertrophy. We demonstrated that the TNNI3 p.R186Q mutation could induce HCM by the dissociation of EGFR and cTnI, which further led to EGFR-dependent increased expression of FASN and abnormal lipid metabolism.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657164","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 use of targeted LNP/mRNA technology to generate functional, transient CAR T cells and treat cardiac injury in vivo","authors":"G. Ellison‐Hughes","doi":"10.20517/jca.2022.05","DOIUrl":"https://doi.org/10.20517/jca.2022.05","url":null,"abstract":"Rurik et al. [1] published in Science provide results from an elegant proof-of-concept study that modified messenger RNA (mRNA) encapsulated in targeted lipid nanoparticles (LNPs) can be delivered intravenously to produce functional engineered T cells in vivo . Specifically, they generated transient anti-fibrotic chimeric antigen receptor (CAR) T cells in vivo by delivering modified mRNA in CD5 T cell-targeted LNPs.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657538","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":"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":" ","pages":""},"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":" ","pages":""},"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":"1 1","pages":""},"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":"2 1","pages":""},"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":" ","pages":""},"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":"1 1","pages":""},"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":"1 1","pages":""},"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":"2 ","pages":""},"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}