The journal of cardiovascular aging最新文献_第9页

Cellular aging and rejuvenation in ischemic heart disease: a translation from basic science to clinical therapy 缺血性心脏病的细胞衰老和年轻化:从基础科学到临床治疗的转化

The journal of cardiovascular aging Pub Date : 2022-01-01 DOI: 10.20517/jca.2021.34

R. Madonna

{"title":"Cellular aging and rejuvenation in ischemic heart disease: a translation from basic science to clinical therapy","authors":"R. Madonna","doi":"10.20517/jca.2021.34","DOIUrl":"https://doi.org/10.20517/jca.2021.34","url":null,"abstract":"Ischemic heart disease and heart failure (HF) remain the leading causes of death worldwide. The inability of the adult heart to regenerate itself following ischemic injury and subsequent scar formation may explain the poor prognosis in these patients, especially when necrosis is extensive and leads to severe left ventricular dysfunction. Under physiological conditions, the crosstalk between cardiomyocytes and cardiac interstitial/vascular cells plays a pivotal role in cardiac processes by limiting ischemic damage or promoting repair processes, such as angiogenesis, regulation of cardiac metabolism, and the release of soluble paracrine or endocrine factors. Cardiovascular risk factors are the main cause of accelerated senescence of cardiomyocytes and cardiac stromal cells (CSCs), causing the loss of their cardioprotective and repairing functions. CSCs are supportive cells found in the heart. Among these, the pericytes/mural cells have the propensity to differentiate, under appropriate stimuli in vitro, into adipocytes, smooth muscle cells, osteoblasts, and chondroblasts, as well as other cell types. They contribute to normal cardiac function and have an antifibrotic effect after ischemia. Diabetes represents a condition of accelerated senescence. Among the new pharmacological armamentarium with hypoglycemic effect, gliflozins have been shown to reduce the incidence of HF and re-hospitalization, probably through the anti-remodeling and anti-senescent effect on the heart, regardless of diabetes. Therefore, either reducing the senescence of CSC or removing senescent cells from the infarcted heart could represent future antisenescence strategies capable of preventing the deterioration of heart function leading to HF.","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":"67657477","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}

引用次数: 2

Oligogenic cardiomyopathy. 寡基因心肌病。

The journal of cardiovascular aging Pub Date : 2022-01-01 DOI: 10.20517/jca.2021.27

Ali J Marian

引用次数: 1

Mitochondrial DAMPs-dependent inflammasome activation during aging induces vascular smooth muscle cell dysfunction and aortic stiffness in low aerobic capacity rats 衰老过程中线粒体damps依赖性炎性体激活诱导低有氧能力大鼠血管平滑肌细胞功能障碍和主动脉僵硬

The journal of cardiovascular aging Pub Date : 2022-01-01 DOI: 10.20517/jca.2022.35

Chandrika Canugovi, M. Stevenson, Aleksandr E. Vendrov, A. Lozhkin, S. Britton, L. Koch, M. Runge, N. Madamanchi

{"title":"Mitochondrial DAMPs-dependent inflammasome activation during aging induces vascular smooth muscle cell dysfunction and aortic stiffness in low aerobic capacity rats","authors":"Chandrika Canugovi, M. Stevenson, Aleksandr E. Vendrov, A. Lozhkin, S. Britton, L. Koch, M. Runge, N. Madamanchi","doi":"10.20517/jca.2022.35","DOIUrl":"https://doi.org/10.20517/jca.2022.35","url":null,"abstract":"Introduction: Low aerobic exercise capacity is an independent risk factor for cardiovascular disease (CVD) and a predictor of premature death. In combination with aging, low aerobic capacity lowers the threshold for CVD. Aim: Since low aerobic capacity and aging have been linked to mitochondrial oxidative stress and dysfunction, we investigated whether aged Low-Capacity Runner (LCR) rats (27 months) had vascular dysfunction compared to High-Capacity Runner (HCR) rats. Methods and Results: A significant decrease in aortic eNOS levels and vasodilation as well as an increase in aortic collagen and stiffness were observed in aged LCR rats compared to age and sex-matched HCR rats. There was a correlation between age-related vascular dysfunction and increased levels of ROS and DNA damage in aortas of LCR rats. Moreover, mitochondrial oxygen consumption, membrane potential, ATP levels, and mitophagy were lower in VSMCs of aged LCR rats. VSMCs from older LCR rats showed AIM2 inflammasome activation. VSMCs of young (4 months old) LCR rats treated with purified mitochondrial damage-associated molecular patterns (DAMP) recapitulated an inflammasome activation phenotype similar to that seen in aged rat VSMCs. Rapamycin, a potent immunosuppressant, induced mitophagy, stimulated electron transport chain activity, reduced inflammasome activity, mitochondrial ROS and DAMP levels in VSMCs from aged LCR rats. MitoTEMPO, a mitochondrial ROS scavenger, was similarly effective on VSMCs from aged rats. Conclusion: The findings suggest that impaired mitophagy and inflammasome activation in the vasculature under conditions of low aerobic exercise capacity during aging results in arterial dysfunction and aortic stiffness. In older adults with reduced aerobic capacity, mitochondrial antioxidants, mitophagy induction, and inflammasome inhibition may be effective therapeutic strategies for enhancing vascular health.","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":"67657254","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}

引用次数: 0

WNT links metabolism and cell cycle in postnatal cardiomyocytes. WNT与出生后心肌细胞的代谢和细胞周期有关。

The journal of cardiovascular aging Pub Date : 2022-01-01 DOI: 10.20517/jca.2022.18

Ivan Menendez-Montes, Hesham A Sadek

引用次数: 0

YAP/TAZ dull the STING of aging. YAP/TAZ淡化老化的刺痛。

The journal of cardiovascular aging Pub Date : 2022-01-01 Epub Date: 2022-08-05 DOI: 10.20517/jca.2022.33

Jamie Francisco, Dominic P Del Re

引用次数: 1

Effects of tamoxifen inducible MerCreMer on gene expression in cardiac myocytes in mice. 他莫昔芬诱导的MerCreMer对小鼠心肌细胞基因表达的影响。

The journal of cardiovascular aging Pub Date : 2022-01-01 Epub Date: 2022-01-05 DOI: 10.20517/jca.2021.30

Leila Rouhi, Siyang Fan, Sirisha M Cheedipudi, Melis Olcum, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

{"title":"Effects of tamoxifen inducible MerCreMer on gene expression in cardiac myocytes in mice.","authors":"Leila Rouhi, Siyang Fan, Sirisha M Cheedipudi, Melis Olcum, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian","doi":"10.20517/jca.2021.30","DOIUrl":"https://doi.org/10.20517/jca.2021.30","url":null,"abstract":"The Cre-LoxP technology, including the tamoxifen (TAM) inducible MerCreMer (MCM), is increasingly used to delineate gene function, understand the disease mechanisms, and test therapeutic interventions. We set to determine the effects of TAM-MCM on cardiac myocyte transcriptome. Expression of the MCM was induced specifically in cardiac myocytes upon injection of TAM to myosin heavy chain 6-MCM (Myh6-Mcm) mice for 5 consecutive days. Cardiac function, myocardial histology, and gene expression (RNA-sequencing) were analyzed 2 weeks after TAM injection. A total of 346 protein coding genes (168 up- and 178 down-regulated) were differentially expressed. Transcript levels of 85 genes, analyzed by a reverse transcription-polymerase chain reaction in independent samples, correlated with changes in the RNA-sequencing data. The differentially expressed genes were modestly enriched for genes involved in the interferon response and the tumor protein 53 (TP53) pathways. The changes in gene expression were relatively small and mostly transient and had no discernible effects on cardiac function, myocardial fibrosis, and apoptosis or induction of double-stranded DNA breaks. Thus, TAM-inducible activation of MCM alters cardiac myocytes gene expression, provoking modest and transient interferon and DNA damage responses without exerting other discernible phenotypic effects. Thus, the effects of TAM-MCM on gene expression should be considered in discerning the bona fide changes that result from the targeting of the gene of interest.","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/PMC8785140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39949695","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}

引用次数: 10

SGLT2 inhibitors in patients with HFpEF: how old is too old? SGLT2抑制剂在HFpEF患者中的应用:多大才算太老?

The journal of cardiovascular aging Pub Date : 2022-01-01 Epub Date: 2022-07-20 DOI: 10.20517/jca.2022.30

Dan Tong

引用次数: 0

To Live in Your Growth Zone, You Need to Leave Your Comfort Zone 为了生活在你的成长区，你需要离开你的舒适区

The journal of cardiovascular aging Pub Date : 2022-01-01 DOI: 10.20517/jca.2022.22

L. Rouhi

引用次数: 0

The TNNI3 p.R186Q mutation is responsible for hypertrophic cardiomyopathy via promoting FASN-stimulated abnormal fatty acid metabolism TNNI3 p.R186Q突变通过促进fasn刺激的异常脂肪酸代谢而导致肥厚性心肌病

The journal of cardiovascular aging Pub Date : 2022-01-01 DOI: 10.20517/jca.2022.29

Linjuan Guo, Yuhao Su, Chen Chen, Qiongqiong Zhou, Yang Shen, Zhenhong Jiang, Xia Yan, Xiaoqing Li, Wen Zhuo, Xiaogang Peng, R. Wan, K. Hong

{"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":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":"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}

引用次数: 1

The use of targeted LNP/mRNA technology to generate functional, transient CAR T cells and treat cardiac injury in vivo 利用靶向LNP/mRNA技术在体内生成功能性、瞬态CAR - T细胞并治疗心脏损伤

The journal of cardiovascular aging Pub Date : 2022-01-01 DOI: 10.20517/jca.2022.05

G. Ellison‐Hughes

引用次数: 0