The journal of cardiovascular aging最新文献

{"title":"The WNT/β-catenin pathway regulates expression of the genes involved in cell cycle progression and mitochondrial oxidative phosphorylation in the postmitotic cardiac myocytes","authors":"Melis Olcum, Sirisha M Cheedipudi, L. Rouhi, S. Fan, Hyun-hwan Jeong, Zhongming Zhao, Priyatansh Gurha, A. Marian","doi":"10.20517/jca.2021.35","DOIUrl":"https://doi.org/10.20517/jca.2021.35","url":null,"abstract":"Introduction: Aging is associated with cardiac myocyte loss, sarcopenia, and cardiac dysfunction. Adult cardiac myocytes are postmitotic cells with an insufficient proliferative capacity to compensate for myocyte loss. The canonical WNT (cWNT) pathway is involved in the regulation of cell cycle reentry in various cell types. The effects of the cWNT pathway on the expression of genes involved in cell cycle reentry in the postmitotic cardiac myocytes are unknown. Aim: The aim of the study was to identify genes whose expression is regulated by the β-catenin, the indispensable component to the cWNT signaling, in the postmitotic myocytes. Methods and Results: Cardiac myocyte-specific tamoxifen-inducible MerCreMer (Myh6-Mcm) mice were used to delete the floxed exon 3 or exons 8 to 13 of the Ctnnb1 gene to induce gain-of-function (GoF) or loss-of-function (LoF) the β-catenin, respectively. Deletion of exon 3 leads to the expression of a stable β-catenin. In contrast, deletion of exons 8–13 leads to the expression of transcriptionally inactive truncated β-catenin, which is typically degraded. GoF or LoF of the β-catenin was verified by reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting, and immunofluorescence. Myocyte transcripts were analyzed by RNA-Sequencing (RNA-Seq) at 4 weeks of age. The GoF of β-catenin was associated with differential expression of ~1700 genes, whereas its LoF altered expression of ~400 genes. The differentially expressed genes in the GoF myocytes were enriched in pathways regulating the cell cycle, including karyokinesis and cytokinesis, whereas the LoF was associated with increased expression of genes involved in mitochondrial oxidative phosphorylation. These findings were validated by RT-PCR in independent samples. Short-term GoF nor LoF of β-catenin did not affect the number of cardiac myocytes, cardiac function, myocardial fibrosis, myocardial apoptosis, or adipogenesis at 4 weeks of age. Conclusion: Activation of the β-catenin of the cWNT pathway in postmitotic myocytes leads to cell cycle reentry and expression of genes involved in cytokinesis without leading to an increase in the number of myocytes. In contrast, suppression of the β-catenin modestly increases the expression of genes involved in oxidative phosphorylation. The findings provide insights into the role of β-catenin of the cWNT pathway in the regulation of cell cycle reentry and oxidative phosphorylation in the postmitotic cardiac myocytes.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43993892","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":"Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications.","authors":"Priyanka Banerjee,&nbsp;Elizabeth A Olmsted-Davis,&nbsp;Anita Deswal,&nbsp;Minh Th Nguyen,&nbsp;Efstratios Koutroumpakis,&nbsp;Nicholas L Palaskas,&nbsp;Steven H Lin,&nbsp;Sivareddy Kotla,&nbsp;Cielito Reyes-Gibby,&nbsp;Sai-Ching J Yeung,&nbsp;Syed Wamique Yusuf,&nbsp;Momoko Yoshimoto,&nbsp;Michihiro Kobayashi,&nbsp;Bing Yu,&nbsp;Keri Schadler,&nbsp;Joerg Herrmann,&nbsp;John P Cooke,&nbsp;Abhishek Jain,&nbsp;Eduardo Chini,&nbsp;Nhat-Tu Le,&nbsp;Jun-Ichi Abe","doi":"10.20517/jca.2022.13","DOIUrl":"https://doi.org/10.20517/jca.2022.13","url":null,"abstract":"<p><p>Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family that is not only a kinase but also a transcriptional co-activator) were vital signaling events that played crucial roles in linking mitochondrial dysfunction, nuclear telomere dysfunction, persistent SASP induction, and atherosclerosis. In this review, we will discuss the role of NAD⁺ depletion in instigating SASP and its downstream signaling and regulatory mechanisms that lead to the premature onset of atherosclerotic cardiovascular diseases in cancer survivors.</p>","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/PMC9258520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9333624","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":"In-depth characterization of a mouse model of postoperative atrial fibrillation.","authors":"Joshua A Keefe,&nbsp;Jose Alberto Navarro-Garcia,&nbsp;Li Ni,&nbsp;Svetlana Reilly,&nbsp;Dobromir Dobrev,&nbsp;Xander H T Wehrens","doi":"10.20517/jca.2022.21","DOIUrl":"https://doi.org/10.20517/jca.2022.21","url":null,"abstract":"<p><strong>Introduction: </strong>Postoperative atrial fibrillation (POAF), characterized as AF that arises 1-3 days after surgery, occurs after 30%-40% of cardiac and 10%-20% of non-cardiac surgeries, and is thought to arise due to transient surgery-induced triggers acting on a preexisting vulnerable atrial substrate often associated with inflammation and autonomic nervous system dysfunction. Current experimental studies often rely on human atrial tissue samples, collected during surgery prior to arrhythmia development, or animal models such as sterile pericarditis and atriotomy, which have not been robustly characterized.</p><p><strong>Aim: </strong>To characterize the demographic, electrophysiologic, and inflammatory properties of a POAF mouse model.</p><p><strong>Methods and results: </strong>A total of 131 wild-type C57BL/6J mice were included in this study. A total of 86 (65.6%) mice underwent cardiothoracic surgery (THOR), which consisted of bi-atrial pericardiectomy with 20 s of aortic cross-clamping; 45 (34.3%) mice underwent a sham procedure consisting of dissection down to but not into the thoracic cavity. Intracardiac pacing, performed 72 h after surgery, was used to assess AF inducibility. THOR mice showed greater AF inducibility (38.4%) compared to Sham mice (17.8%, <i>P</i> = 0.027). Stratifying the cohort by tertiles of age showed that the greatest risk of POAF after THOR compared to Sham occurred in the 12-19-week age group. Stratifying by sex showed that cardiothoracic (CT) surgery increased POAF risk in females but had no significant effect in males. Quantitative polymerase chain reaction of atrial samples revealed upregulation of transforming growth factor beta 1 <i>(TGF-β1)</i> and interleukin 6 (IL6) and 18 (IL18) expression in THOR compared to Sham mice.</p><p><strong>Conclusion: </strong>Here, we demonstrate that the increased POAF risk associated with CT surgery is most pronounced in female and 12-19-week-old mice, and that the expression of inflammatory cytokines is upregulated in the atria of THOR mice prone to inducible AF.</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/PMC9632544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40682907","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":"Pulse wave velocity: why is it important to know to estimate?","authors":"A. Reddy, G. Taffet","doi":"10.20517/jca.2021.36","DOIUrl":"https://doi.org/10.20517/jca.2021.36","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":"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":"67657488","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":"Mechanisms and implications of sex differences in cardiac aging.","authors":"Aykhan Yusifov, Kathleen C Woulfe, Danielle R Bruns","doi":"10.20517/jca.2022.01","DOIUrl":"10.20517/jca.2022.01","url":null,"abstract":"<p><p>Aging promotes structural and functional remodeling of the heart, even in the absence of external factors. There is growing clinical and experimental evidence supporting the existence of sex-specific patterns of cardiac aging, and in some cases, these sex differences emerge early in life. Despite efforts to identify sex-specific differences in cardiac aging, understanding how these differences are established and regulated remains limited. In addition to contributing to sex differences in age-related heart disease, sex differences also appear to underlie differential responses to cardiac stress such as adrenergic activation. Identifying the underlying mechanisms of sex-specific differences may facilitate the characterization of underlying heart disease phenotypes, with the ultimate goal of utilizing sex-specific therapeutic approaches for cardiac disease. The purpose of this review is to discuss the mechanisms and implications of sex-specific cardiac aging, how these changes render the heart more susceptible to disease, and how we can target age- and sex-specific differences to advance therapies for both male and female patients.</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/PMC9004711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47654352","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":"Promoting healthy cardiovascular aging: emerging topics.","authors":"Zachary S Clayton, Daniel H Craighead, Sanna Darvish, McKinley Coppock, Katelyn R Ludwig, Vienna E Brunt, Douglas R Seals, Matthew J Rossman","doi":"10.20517/jca.2022.27","DOIUrl":"10.20517/jca.2022.27","url":null,"abstract":"<p><p>The development of age-related cardiovascular (CV) dysfunction increases the risk of CV disease as well as other chronic age-associated disorders, including chronic kidney disease, and Alzheimer's disease and related dementias. Major manifestations of age-associated CV dysfunction that increase disease risk are vascular dysfunction, primarily vascular endothelial dysfunction and arterial stiffening, and elevated systolic blood pressure. Declines in nitric oxide bioavailability secondary to increased oxidative stress and inflammation are established mechanisms of CV dysfunction with aging. Moreover, fundamental mechanisms of aging, termed the \"hallmarks of aging\" extend to the CV system and, as such, may be considered \"hallmarks of CV aging\". These mechanisms represent viable therapeutic targets for treating CV dysfunction with aging. Healthy lifestyle behaviors, such as regular aerobic exercise and certain dietary patterns, are considered \"first-line\" strategies to prevent and/or treat age-associated CV dysfunction. Despite the well-established benefits of these strategies, many older adults do not meet the recommended guidelines for exercise or consume a healthy diet. Therefore, it is important to establish alternative and/or complementary evidence-based approaches to prevent or reverse age-related CV dysfunction. Targeting fundamental mechanisms of CV aging with interventions such as time-efficient exercise training, food-derived molecules, termed nutraceuticals, or select synthetic pharmacological agents represents a promising approach. In the present review, we will highlight emerging topics in the field of healthy CV aging with a specific focus on how exercise, nutrition/dietary patterns, nutraceuticals and select synthetic pharmacological compounds may promote healthy CV aging, in part, by targeting the hallmarks of CV aging.</p>","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/PMC9632540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9888980","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":"Principles of scientific research conduct, peer review, and publication: an editor's perspective.","authors":"Ali J Marian","doi":"10.20517/jca.2021.37","DOIUrl":"https://doi.org/10.20517/jca.2021.37","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":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39826181","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":"Male carriers of HLA-C*04:01 have increased risk of cardiac injury in COVID-19","authors":"P. Suwalski, Michele Violano, Melina Müller, D. Patriki, C. Thibeault, C. Quedenau, Xiaomin Wang, Zehra Karadeniz, J. Saccomanno, Jan-Moritz Doehn, R. Hübner, B. Hinzmann, H. Beer, B. Wiggli, Sandra Siemann, N. Suttorp, M. Witzenrath, S. Hippenstiel, C. Skurk, W. Poller, L. Sander, F. Kurth, Tatiana Borodina, T. Guettouche, U. Landmesser, B. Heidecker","doi":"10.20517/jca.2022.19","DOIUrl":"https://doi.org/10.20517/jca.2022.19","url":null,"abstract":"Identification of factors that lead to the severe clinical course of COVID-19 is crucial for timely allocation of resources. The purpose of this study was to evaluate possible sex differences in cardiac injury associated with HLA-C*04:01. High sensitivity troponin T on admission (hs-TnTa) and maximum high sensitivity troponin T (hs-TnTmax) were used to assess for cardiac injury in patients with COVID-19 (n = 435). We tested for the association of elevated hs-TnT with HLA-C* 04:01 and evaluated for potential sex-specific differences. An association between hs-TnTa and the severity of clinical course was identified. In addition, our study revealed that hs-TnTmax was higher in men who were carriers of HLA-C*04:01 compared to men without the risk allele. Male carriers of HLA-C*04:01 with COVID-19 developed higher hs-TnTmax, suggesting a larger extent of cardiac injury. This association suggests the presence of different pathomechanisms in COVID-19 based on sex.","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":"67657100","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":"Pursuing the physician-scientist path to satisfy research curiosity and passion for patient care","authors":"L. Rouhi","doi":"10.20517/jca.2022.39","DOIUrl":"https://doi.org/10.20517/jca.2022.39","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":"67657272","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":"Physical exercise in older patients with heart failure","authors":"Hirofumi Tanaka","doi":"10.20517/jca.2021.23","DOIUrl":"https://doi.org/10.20517/jca.2021.23","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":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657408","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}