American journal of physiology. Heart and circulatory physiology最新文献

{"title":"Emerging roles of noncoding RNAs in cardiovascular pathophysiology.","authors":"Malak Abbas, Amadou Gaye","doi":"10.1152/ajpheart.00681.2024","DOIUrl":"10.1152/ajpheart.00681.2024","url":null,"abstract":"<p><p>This review comprehensively examines the diverse roles of noncoding RNAs (ncRNAs) in the pathogenesis and treatment of cardiovascular disease (CVD), focusing on microRNA (miRNA), long noncoding RNA (lncRNA), piwi-interacting RNA (piRNA), small-interfering RNA (siRNA), circular RNA (circRNA), and vesicle-associated RNAs. These ncRNAs are integral regulators of key cellular processes, including gene expression, inflammation, and fibrosis, and they hold great potential as both diagnostic biomarkers and therapeutic targets. The review highlights novel insights into how these RNA species, particularly miRNAs, lncRNAs, and piRNAs, contribute to various CVDs such as hypertension, atherosclerosis, and myocardial infarction. In addition, it explores the emerging role of extracellular vesicles (EVs) in intercellular communication and their therapeutic potential in cardiovascular health. The review underscores the need for continued research into ncRNAs and RNA-based therapies, with a focus on advancing delivery systems and expanding personalized medicine approaches to improve cardiovascular outcomes.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H603-H621"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in aortic valve inflammation and remodeling in chronic severe aortic regurgitation.","authors":"Carolina Tiraplegui, Mattie Garaikoetxea, Alba Sádaba, Susana San Ildefonso-García, Miriam Goñi-Olóriz, Amaya Fernández-Celis, Ernesto Martín-Núñez, Virginia Álvarez, Rafael Sádaba, Vidhu Anand, Eva Jover, Adela Navarro, Natalia López-Andrés","doi":"10.1152/ajpheart.00645.2024","DOIUrl":"10.1152/ajpheart.00645.2024","url":null,"abstract":"<p><p>Aortic regurgitation (AR) is more prevalent in males, although cellular and molecular mechanisms underlying the sex differences in prevalence and pathophysiology are unknown. This study evaluates the impact of sex on aortic valve (AV) inflammation and remodeling and the cellular differences in valvular interstitial cells (VICs) and valvular endothelial cells (VECs) in patients with AR. A total of 144 patients (27.5% female) with severe chronic AR were included. AVs were analyzed by imaging, histological, and molecular biology techniques (ELISA, RT-PCR). VICs and VECs isolated from patients with AR were characterized and further treated with transforming growth factor (TGF)-β. Anatomically, male had smaller index aortic dimensions and greater AV thickness. Proteome profiler analyzes in AVs (<i>n</i> = 40/sex) evidenced higher expression of inflammatory markers in male and that was further validated (interleukins, chemokines). Histological composition showed higher expression of inflammatory mediators and collagen thick fibers in AVs from male. Male VICs and VECs secreted higher levels of inflammatory markers than female cells. Interestingly, male VICs produced higher amounts of collagen type I and lower fibronectin and aggrecan, whereas male VECs secreted lower decorin. TGF-β exclusively enhanced inflammation in male VICs and decorin and aggrecan in female VICs. Compared with male, AVs from female were thinner, less inflamed, and fibrotic. VICs seem to be the key cell type responsible for the sex-differences. Valvular inflammation associated with an active remodeling process could be a key pathophysiological process involved in AR.<b>NEW & NOTEWORTHY</b> The pathogenesis of chronic aortic regurgitation (AR) is different in male and female. Female patients with AR showed less aortic valve inflammation and collagen accumulation as compared with male. Valvular cells from female patients secreted less inflammatory molecules and collagen and higher levels of proteoglycans. Valvular interstitial cells from females were more sensitive to transforming growth factor (TGF)-β-induced proteoglycans secretion. Our study opens a new perspective oriented toward sex-specific molecular pathways and therapeutic targets in chronic severe AR.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H693-H710"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Favorable alterations in ventricular-arterial interactions across the menstrual cycle in healthy premenopausal women.","authors":"Ninette Shenouda, Joseph M Stock, Nicholas V Chouramanis, Zoe R Lincoln, Megan M Wenner, Julio A Chirinos, David G Edwards","doi":"10.1152/ajpheart.00363.2024","DOIUrl":"10.1152/ajpheart.00363.2024","url":null,"abstract":"<p><p>Increased arterial wave reflections can increase left ventricular wasted pressure effort (WPE) and cardiovascular disease risk. Naturally menstruating women experience fluctuations in sex hormones with known cardioprotective effects. We sought to determine whether hormonal fluctuations alter arterial hemodynamics or wave reflections, and thereby WPE, or contribute to sex differences. We hypothesized that premenopausal women would have favorable wave reflection changes and reduced WPE during high- versus low-hormone cycle phases and compared with men. We tested 13 women (28 ± 7 yr) during the early follicular (EF, <i>cycle days 3</i> ± <i>1</i>), late follicular (LF, <i>cycle days 12</i> ± <i>2</i>), and mid-luteal (ML, <i>cycle days 22</i> ± <i>3</i>) phases. Eleven men (28 ± 3 yr) underwent time-matched visits. Sex hormones and arterial hemodynamics were measured at all visits. Wave reflection indices and WPE were assessed via aortic pressure-flow analyses. We observed sex-by-visit interactions for WPE and total peripheral resistance (TPR; both <i>P</i> < 0.01). Women showed favorable reductions in WPE (EF: 2,758 ± 966 and LF: 2,489 ± 1,230 vs. ML: 1,954 ± 1,085 mmHg·ms, both <i>P</i> < 0.05) and TPR (EF: 1,885 ± 271 vs. ML: 1,699 ± 255 dyn·s·cm^-5, <i>P</i> = 0.01) from low- to high-hormone phases. These reductions were not observed in men and were not paralleled in classic wave reflection indices (<i>P</i> > 0.05). Increased estradiol predicted a reduction in TPR (<i>R</i>² = 0.45, <i>P</i> < 0.001), whereas TPR, reflected wave amplitude, and timing of wave reflection predicted reductions in WPE (<i>R</i>² = 0.71, <i>P</i> < 0.001). These data implicate a role of estradiol on the peripheral vasculature, leading to reduced left ventricular WPE, suggesting a need to consider cycle phases when assessing ventricular load in naturally menstruating women.<b>NEW & NOTEWORTHY</b> Using aortic pressure-flow analyses, we demonstrate favorable reductions in left ventricular wasted pressure effort across menstrual cycle phases in healthy premenopausal women, but not across time-matched visits in men. Increases in estradiol were related to changes in total peripheral resistance, which, along with reflected wave amplitude and timing, leads to a reduced wasted pressure effort. Our findings suggest a need to consider sex hormones and cycle phases when assessing ventricular load in naturally menstruating women.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H648-H657"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling hidden dangers: quantitative analysis of ischemic risks in high-risk patients with ASCVD and dyslipidemia.","authors":"Shih-Hsien Sung, Min-Ji Charng","doi":"10.1152/ajpheart.00555.2024","DOIUrl":"10.1152/ajpheart.00555.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H415-H418"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical applications for lipid mediators in STEMI.","authors":"Hiroe Toba, Denan Jin, Shinji Takai","doi":"10.1152/ajpheart.00013.2025","DOIUrl":"10.1152/ajpheart.00013.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H441-H443"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel endothelial-specific adhesion molecule deficiency influences on pulmonary vascular function potentially contributing to cardiovascular disease progression.","authors":"Michael S Wolin","doi":"10.1152/ajpheart.00071.2025","DOIUrl":"10.1152/ajpheart.00071.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H444-H446"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of mechanosignaling in the control of myocardial mass.","authors":"Maicon Landim-Vieira, Paula F Nieto Morales, Summer ElSafty, Aida Rahimi Kahmini, Mark J Ranek, Christopher Solís","doi":"10.1152/ajpheart.00277.2024","DOIUrl":"10.1152/ajpheart.00277.2024","url":null,"abstract":"<p><p>Regulation of myocardial mass is key for maintaining cardiovascular health. This review highlights the complex and regulatory relationship between mechanosignaling and myocardial mass, influenced by many internal and external factors including hemodynamic and microgravity, respectively. The heart is a dynamic organ constantly adapting to changes in workload (preload and afterload) and mechanical stress exerted on the myocardium, influencing both physiological adaptations and pathological remodeling. Mechanosignaling pathways, such as the mitogen-activated protein kinases (MAPKs) and the phosphoinositide 3-kinases and serine/threonine kinase (PI3K/Akt) pathways, mediate downstream effects on gene expression and play key roles in transducing mechanical cues into biochemical signals, thereby modulating cellular processes, including control of myocardial mass. Dysregulation of these processes can lead to pathological cardiac remodeling, such as hypertrophic cardiomyopathy. Furthermore, recent studies have highlighted the importance of protein quality control mechanisms, such as the ubiquitin-proteasome system, in settings of extreme physiological conditions that alter the heart workload such as pregnancy and microgravity. Overall, this review provides a thorough insight into how mechanical signals are converted into chemical signals to regulate myocardial mass in both healthy and diseased conditions.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H622-H638"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemerin is a new sex-specific target in aortic stenosis concomitant with diabetes regulated by the aldosterone/mineralocorticoid receptor axis.","authors":"Miriam Goñi-Olóriz, Mattie Garaikoetxea Zubillaga, Susana San Ildefonso-García, Amaya Fernández-Celis, Paula Castillo, Adela Navarro, Virginia Álvarez, Rafael Sádaba, Eva Jover, Ernesto Martín-Núñez, Natalia López-Andrés","doi":"10.1152/ajpheart.00763.2024","DOIUrl":"10.1152/ajpheart.00763.2024","url":null,"abstract":"<p><p>Diabetes mellitus (DM) increases the risk of aortic stenosis (AS) and worsens its pathophysiology in a sex-specific manner. Aldosterone/mineralocorticoid receptor (Aldo/MR) pathway participates in the early stages of AS and in other diabetic-related cardiovascular complications. We aim to identify new sex-specific Aldo/MR targets in AS complicated with DM. We performed discovery studies using Olink Proteomics technology in 87 AS patient-derived aortic valves (AVs) (<i>N</i> = 28 and <i>N</i> = 19 nondiabetic and diabetic men; <i>N</i> = 32 and <i>N</i> = 8 nondiabetic and diabetic women, respectively) and human cytokine array (<i>N</i> = 24 AVs/sex/condition). Both approaches revealed chemerin as a target differentially upregulated in AVs from male diabetic patients, further validated in a cohort of stenotic AVs (<i>N</i> = 283, 27.6% DM, 59.4% men). Valvular chemerin levels are directly correlated with valve interstitial cell (VIC) activation, MR, inflammation, angiogenesis, and calcification markers exclusively in diabetic men. In vitro, Aldo (10^-8 M) treatment exclusively increased chemerin levels in valve interstitial cells (VICs) from male patients with DM. Aldo also upregulated inflammatory, angiogenic, and osteogenic markers in DM and non-DM donors' VICs, which were prevented by MR antagonism. Increased glucose levels in cell media upregulated chemerin in VICs from male diabetic patients. Overall, <i>RARRES2</i>-knockdown in male diabetic VICs resulted in the downregulation of inflammatory, angiogenic, and osteogenic markers and blocked Aldo-induced responses in high glucose conditions. These data suggest the Aldo/MR pathway selectively increases chemerin in VICs from diabetic men, promoting inflammation, angiogenesis, and calcification associated with AS progression.<b>NEW & NOTEWORTHY</b> Chemerin is upregulated in AV of male diabetic patients with AS, correlating with valve degeneration markers and influenced by Aldo/MR activation. This highlights chemerin as a sex-specific target for AS therapy.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H639-H647"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo effects of cardiomyocyte-specific β-1 blockade on afterload- and frequency-dependent cardiac performance.","authors":"Genri Numata, Yu Otsu, Shun Nakamura, Masayuki Toyoda, Hiroyuki Tokiwa, Yusuke Adachi, Taro Kariya, Kota Sueo, Mayo Shigeta, Takaya Abe, Tetsuo Sasano, Atsuhiko Naito, Issei Komuro, Eiki Takimoto","doi":"10.1152/ajpheart.00795.2024","DOIUrl":"10.1152/ajpheart.00795.2024","url":null,"abstract":"<p><p>Pharmacologic β-blockade is a well-established therapy for reducing adverse effects from sympathetic overactivity in cardiovascular diseases, such as heart failure. Despite decades of research efforts, in vivo cardiac functional studies using genetic animal models remain scant. We generated a mouse model of cardiomyocyte-specific deletion (cKO) of β-1 adrenergic receptor (ADRB1), the primary subtype expressed in cardiac myocytes, and demonstrated the role of ADRB1 in the maintenance of cardiac function at baseline and during exposure to increase in cardiac afterload by transient aortic occlusion and increasing heart rates (HRs) via atrial pacing. cKO hearts showed mildly depressed baseline left ventricular (LV) function, including slower HR, decreased contractility (dP/dt max/IP), and prolonged relaxation (Tau) in both sexes. Exposure to increased LV afterload depressed LV function in either genotype similarly; however, the functional recovery following the removal of the afterload was severely impaired in cKO hearts, whereas cardiac function was immediately normalized in wild-type (WT) hearts. When HR was altered from 400 to 700 beats/min, cKO hearts were deficient in HR-dependent improvement of cardiac contractility and relaxation, known as positive force-frequency relationship, that was evident in WT hearts. Enhanced phosphorylation of phospholamban by the HR increase was markedly blunted in cKO myocardium versus wild types, whereas CaMKII phosphorylation was comparable between the genotypes, suggesting the critical involvement of PKA. These results provide the first experimental evidence for the role of ADRB1 in cardiomyocytes for maintaining cardiac function at baseline and during acute stress, providing a clinical perspective relating to the management of patients on β-blockers.<b>NEW & NOTEWORTHY</b> Although the benefits of β-1 adrenergic receptor (ADRB1) blockade to cardiovascular disease are established, in vivo role for cardiomyocyte ADRB1 remains undetermined. Generating cardiomyocyte-specific <i>ADRB1</i> knockout mice, we show that ADRB1 is pivotal to cardiac functional recovery from afterload elevation and heart rate-dependent functional enhancement as well as baseline performance. Our findings highlight the importance of cardiomyocyte ADRB1 in cardiac stress adaptability, which is of clinical importance in the management of patients on β-blockers.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H543-H549"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2 purinergic receptors at the heart of pathological left ventricular remodeling following acute myocardial infarction.","authors":"Ana Valéria Vinhais da Silva, Simon Chesseron, Oumnia Benouna, Jérôme Rollin, Sébastien Roger, Thierry Bourguignon, Stéphanie Chadet, Fabrice Ivanes","doi":"10.1152/ajpheart.00599.2024","DOIUrl":"10.1152/ajpheart.00599.2024","url":null,"abstract":"<p><p>Pathological left ventricular remodeling is a complex process following an acute myocardial infarction, leading to architectural disorganization of the cardiac tissue. This phenomenon is characterized by sterile inflammation and the exaggerated development of fibrotic tissue, which is noncontractile and poorly conductive, responsible for organ dysfunction and heart failure. At present, specific therapies are lacking for both prevention and treatment of this condition, and no biomarkers are currently validated to identify at-risk patients. Physiopathological understanding of this process is limited, probably due to the combination of the multicellular responses involved that are initially necessary for tissue healing but may be detrimental in the longer term. Current research focuses on understanding and modulating the inflammatory response, a key aspect of the tissue healing process. Inflammation is triggered by the release of inflammatory mediators from cardiomyocytes undergoing cell death in the context of ischemia-reperfusion injury. Among them, extracellular ATP is a strong mediator of inflammation through the activation of P2 purinergic receptors, regulating the behavior of all the cellular actors of the postmyocardial infarction response and impacting organ function and recovery. Rather than considering each cellular protagonist independently, this review provides an integrated overview of the inflammatory and tissue response to myocardial infarction by members of the P2 receptor family. Finally, it explores the possibility of reducing pathological left ventricular remodeling through the modulation of these receptors and their associated signaling pathways.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H550-H564"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}