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

{"title":"From signal to action: the roles of β₁-adrenergic receptors in cardiac function and disease.","authors":"W Glen Pyle","doi":"10.1152/ajpheart.00151.2025","DOIUrl":"10.1152/ajpheart.00151.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H830-H831"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583797","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":"Role of shear stress-induced red blood cell released ATP in atherosclerosis.","authors":"Yunpei Zhang, Haoyu Sun, Aayush Gandhi, Yong Du, Saman Ebrahimi, Yanyan Jiang, Sulei Xu, Hope Uwase, Alane Seidel, Sarah S Bingaman, Amy C Arnold, Christian Nguyen, Wei Ding, Matthew D Woolard, Ryan Hobbs, Prosenjit Bagchi, Pingnian He","doi":"10.1152/ajpheart.00875.2024","DOIUrl":"10.1152/ajpheart.00875.2024","url":null,"abstract":"<p><p>Altered hemodynamics is a key factor for atherosclerosis. For decades, endothelial cell (EC) responses to fluid-generated wall shear stress have been the central focus for atherogenesis. However, circulating blood is not a cell-free fluid, it contains mechanosensitive red blood cells (RBCs) that are also subjected to altered hemodynamics and release a large amount of ATP, but their impact on atherosclerosis has been overlooked. The focus of this study is the role of shear stress (SS)-induced RBC-released ATP in atherosclerosis. Hypercholesterolemic mouse models with and without RBC-Pannexin 1 deletion were used for the study. Results showed that SS-induced release of ATP from RBCs was at µM concentrations, three-orders of magnitude higher than that from other cell types. Suppression of RBC-released ATP via deletion of Pannexin 1, a mechanosensitive ATP-permeable channel, reduced high-fat diet-induced aortic plaque burden by 40%-60%. Importantly, the location and the extent of aortic atherosclerotic lesions spatially matched with the ATP deposition profile at aortic wall predicted by a computational fluid dynamic (CFD) model. Furthermore, hypercholesterolemia increases EC susceptibility to ATP with potentiated increase in [Ca²⁺]_i, an initial signaling for aortic EC barrier dysfunction, and an essential cause for lipid accumulation and inflammatory cell infiltration. The computational prediction also provides a physics-based explanation for RBC-released ATP-induced sex disparities in atherosclerosis. Our study reveals an important role of RBC-released ATP in the initiation and progression of atherosclerosis. These novel findings provide a more comprehensive view of how altered hemodynamics and systemic risk factors synergistically contribute to atherosclerosis.<b>NEW & NOTEWORTHY</b> This study reveals that, in addition to fluid-derived wall shear stress, the disturbed blood flow-induced release of ATP from mechanosensitive red blood cells (RBCs), the major cellular components of blood, along with hypercholesterolemia-induced increases in endothelial cell susceptibility to ATP contribute significantly to the initiation and progression of atherosclerosis. These novel findings advance our current understanding of how altered hemodynamics and hypercholesterolemia synergistically contribute to atherosclerosis for the first time with the inclusion of RBCs.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H774-H791"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466655","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":"Immune checkpoint inhibitor-associated myocarditis: a historical and comprehensive review.","authors":"Garrett Jensen, Xinjie Wang, Jacob Kuempel, Nicolas Palaskas, Zhishi Chen, Wei Yu, Yanping Chen, Haseeb Mohammad, Weijia Luo, Jiang Chang","doi":"10.1152/ajpheart.00687.2024","DOIUrl":"10.1152/ajpheart.00687.2024","url":null,"abstract":"<p><p>The most fatal side effect associated with revolutionary immune checkpoint inhibitor (ICI) cancer therapies is myocarditis, a rare and devastating complication with a mortality rate approaching 40%. This review comprehensively examines the limited knowledge surrounding this recently recognized condition, emphasizing the absence of evidence-based therapeutic strategies, diagnostic modalities, and reliable biomarkers that hinder effective management. It explores advancements in preclinical models that are uncovering disease mechanisms and enabling the identification of therapeutic targets. These efforts have informed the design of early clinical trials aimed at reducing mortality. With the growing prevalence of ICI therapies in oncology, addressing critical gaps, such as long-term outcomes and risk stratification, has become increasingly urgent. By synthesizing current evidence, this work seeks to enhance understanding and guide the development of strategies to improve patient outcomes and ensure the continued safe use of ICIs in cancer care.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H734-H751"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381527","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":"Salsalate negatively impacts microvascular function in women with endometriosis.","authors":"Auni C Williams, Virginia G Content, Lacy M Alexander","doi":"10.1152/ajpheart.00012.2025","DOIUrl":"10.1152/ajpheart.00012.2025","url":null,"abstract":"<p><p>Women with endometriosis, an inflammatory disease, are at increased risk of cardiovascular disease and demonstrate impaired microvascular endothelial function, characterized by reduced nitric oxide (NO)-mediated vasodilation. In some clinical cohorts, nuclear factor-kappa B (NFκB) inhibition with salsalate improves endothelial function. We hypothesized that salsalate would improve cutaneous microvascular endothelial function in women with endometriosis. Following placebo or salsalate (3,000 mg·day^-1 for 5 days), four intradermal microdialysis probes were placed in 11 women (33 ± 7 yr) with endometriosis. Local heating units (set to 33°C) and laser-Doppler flowmetry (red blood cell flux) probes were placed over the probes. Increasing doses of acetylcholine (ACh; dissolved in lactated Ringer's solution) were perfused, alone (control) or coperfused with: <i>N</i>^G-nitro-l-arginine methyl ester (l-NAME), atorvastatin (statin), or l-NAME + statin (combo). Maximal vasodilation was then induced (local heat at 43°C + sodium nitroprusside perfusion). Data were normalized as percentage of maximal cutaneous vascular conductance (CVC_%max red blood cell flux/mean arterial pressure). To measure macrovascular endothelial function, flow-mediated dilation (FMD) was additionally performed. During placebo, coperfusion with statin did not impact the CVC_%max ACh dose-response (<i>P</i> = 0.93). Oral salsalate attenuated the CVC_%max response to ACh perfusion alone (<i>P</i> < 0.01) but did not impact the l-NAME site (<i>P</i> = 0.09). Salsalate significantly augmented the CVC_%max response of the statin site (<i>P</i> < 0.01) but did not affect the combo site response (<i>P</i> = 1.00). FMD was not different between treatments (<i>P</i> = 0.79). Salsalate treatment impairs vasodilation in the cutaneous microcirculation in women with endometriosis through non-NO-dependent mechanisms.<b>NEW & NOTEWORTHY</b> Our results show that oral salsalate treatment negatively impacts microvascular function but does not alter macrovascular function. In contrast to the majority of other clinical populations with endothelial dysfunction, salsalate treatment reduces microcirculatory function through non-NO-dependent mechanisms in women with endometriosis.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H915-H922"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of microRNA-146a-5p, but not -155-5p and -29b-5p, in left ventricular remodeling and dysfunction in spontaneously hypertensive rats.","authors":"Siluleko A Mkhize, Sulé Gunter, Ashmeetha Manilall, Lebogang Mokotedi, Kgotso L Mosoma, Refentshe Nthlane, Aletta M E Millen, Frederic S Michel","doi":"10.1152/ajpheart.00696.2024","DOIUrl":"10.1152/ajpheart.00696.2024","url":null,"abstract":"<p><p>The contribution of microRNAs remains poorly understood in the context of hypertensive cardiac pathology. The role of miR-146a-5p, miR-155-5p, and miR-29b-5p in cardiac hypertrophy and dysfunction was investigated in spontaneously hypertensive rats (SHRs). Seven-month-old SHR (<i>n</i> = 7 male, <i>n</i> = 9 female) and normotensive Wistar Kyoto rats (WKY; <i>n</i> = 7 male, <i>n</i> = 9 female) underwent echocardiography. Plasma concentrations of inflammatory markers were measured by ELISA. Interstitial and perivascular fibrosis and percentage macrophage infiltration were determined by histology. Left ventricular (LV) mRNA expressions of cardiac remodeling markers and miRNA expressions were determined by RT-PCR. Circulating vascular cell adhesion molecule-1 (VCAM-1), macrophage infiltration, interstitial and perivascular fibrosis, relative wall thickness (RWT), early diastolic mitral inflow to tissue lengthening velocity at lateral mitral annulus (E/e'), and LV mRNA expression of <i>NFKBIA</i> and <i>SOD2</i> were greater in SHRs. MidFS, e', and a' were lower in SHRs. Expression of <i>LOX1</i>, <i>Col1a/Col3a</i> ratio, circulating c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and RWT were greater in females. No difference in miR-29b-5p expression was noted. MiR-155-5p expression was lower in female and associated with stroke volume and absolute heart and LV masses. MiR-146a-5p expression was greater in SHRs and associated with systolic blood pressure (SBP), circulating VCAM-1, macrophage infiltration, interstitial fibrosis, normalized heart and LV masses, RWT, and a'. MiR-146a-5p was also associated with circulating VCAM-1 after adjustments for SBP. In addition, greater expression of miRNA-146a-5p reversed the relationship between circulating VCAM-1 and macrophage infiltration. Changes in the expression of miR-155-5p may be involved with a cardiac phenotype related to sexual dimorphism. Conversely, upregulation of miR-146a-5p expression may act as a countermechanism induced by myocardial inflammation in the setting of reactive fibrosis, established LV hypertrophy, and impaired diastolic function.<b>NEW & NOTEWORTHY</b> We investigated roles of microRNAs-146a-5p, -155-5p, and -29b-5p in development of cardiac hypertrophy and dysfunction in SHRs. We showed that miR-146a-5p expression was upregulated in SHRs and positively associated with indices of concentric LVH and diastolic dysfunction, potentially as countermechanism in response to myocardial inflammation, whereas miR-155-5p was expressed in a manner consistent with sexual dimorphism. Our data may offer novel insights on involvement of miRNAs in myocardial inflammation in hypertension-induced cardiac hypertrophy and dysfunction.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H885-H899"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539933","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":"Regulatory roles of PIWI-interacting RNAs in cardiovascular disease.","authors":"Pushkar Shivam, Destiny Ball, Ayorinde Cooley, Inmar Osi, Kayla J Rayford, Said B Gonzalez, Alayjha D Edwards, Antonisha R McIntosh, Jessica Devaughn, Jada P Pugh-Brown, Smita Misra, Annet Kirabo, Aramandla Ramesh, Merry L Lindsey, Amos M Sakwe, Amadou Gaye, Antentor Hinton, Pamela M Martin, Pius N Nde","doi":"10.1152/ajpheart.00833.2024","DOIUrl":"10.1152/ajpheart.00833.2024","url":null,"abstract":"<p><p>Cardiovascular disease remains the number one cause of death worldwide. Across the spectrum of cardiovascular pathologies, all are accompanied by changes in gene expression profiles spanning a variety of cellular components of the myocardium. Alterations in gene expression are regulated by small noncoding RNAs (sncRNAs), with P-element-induced WImpy testis (PIWI)-interacting RNAs (piRNAs) being the most abundant of the sncRNAs in the human genome. Composed of 21-35 nucleotides in length with a protective methyl group at the 3' end, piRNAs complex with highly conserved RNA-binding proteins termed PIWI proteins to recruit enzymes used for histone, DNA, RNA, and protein modifications. Thus, specific piRNA expression patterns can be exploited for early clinical diagnosis of cardiovascular disease and the development of novel RNA therapeutics that may improve cardiac health outcomes. This review summarizes the latest progress made on understanding how piRNAs regulate cardiovascular health and disease progression, including a discussion of their potential in the development of biomarkers and therapeutics.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H991-H1004"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic underpinnings of AGEs-RAGE via DIAPH1 in ischemic, diabetic, and failing hearts.","authors":"Gautham Yepuri, Syed Nurul Hasan, Vikas Kumar, Michaele B Manigrasso, Gregory Theophall, Alexander Shekhtman, Ann Marie Schmidt, Ravichandran Ramasamy","doi":"10.1152/ajpheart.00685.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00685.2024","url":null,"abstract":"<p><p>Diabetes is a major risk factor for cardiovascular diseases. Patients with diabetes are at greater risk for morbidity and mortality post myocardial infarction. As the epidemic of diabetes continues at an alarming pace, identification of specific therapeutic interventions to protect diabetic patients from the devastating consequences of myocardial infarction is an urgent need. Advanced glycation end products (AGEs), the products of nonenzymatic glycation and oxidation of proteins and lipids, accumulate in the diabetic circulation and heart. The interaction of AGEs with its key receptor, receptor for AGE or RAGE, contributes to cardiac injury and dysfunction. The discovery that intracellular domain of RAGE binds to the formin, DIAPH1, and that DIAPH1 is essential for RAGE ligand-mediated signal transduction, unveiled the specific cellular means by which RAGE functions and highlights a new target for therapeutic interruption of pathological RAGE signaling during myocardial infarction. This review delves into intrinsic mechanisms by which AGE-RAGE axis via RAGE-DIAPH1 driven DIAPH1-Mitofusin2 (MFN2) interaction modulates pathogenic inter-organelle communications and opens opportunities for intensive studies to uncover the comprehensive mechanisms that drive injury-provoking actions from the intracellular space. This review illustrates the potential therapeutic cardioprotective benefits of antagonism of RAGE-DIAPH1interactions in the diabetic heart.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707920","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: A key but underexplored player in post-myocardial infarction healing.","authors":"Cécile Dufeys, Luc Bertrand, Christophe Beauloye, Sandrine Horman","doi":"10.1152/ajpheart.00179.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00179.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699350","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":"No effect of stage 1 hypertension or hypertensive medication on critical environmental limits (PSU HEAT Project).","authors":"Olivia K Leach, Kat G Fisher, Rachel M Cottle, W Larry Kenney","doi":"10.1152/ajpheart.00038.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00038.2025","url":null,"abstract":"<p><p>Middle-aged and older individuals with hypertension are often considered to be at increased risk during environmental heat waves due to blunted increases in skin blood flow and subsequently elevated core temperatures. Additionally, common antihypertensive medications (i.e., ACE inhibitors, diuretics, and beta blockers) can independently impair heat loss mechanisms, reportedly heightening heat related risk. If these groups are at increased risk, differences should be observed in the environmental conditions in which thermal balance can occur. Identifying critical environmental limits is an integrative method to determine the conditions that separate safe from unsafe heat exposure. Seventy-two participants (F=43) (63±11 yrs; range: 40-92 yrs) were exposed to progressive heat stress at a low metabolic rate. Thirty-seven of the participants were hypertensive (defined by current AHA guidelines for stage 1 hypertension) and 15 participants were taking antihypertensive medications. Experiments were conducted in both hot-dry (HD; up to 53°C, ≤25% rh) and warm-humid (WH; ~35°C, ≥50% rh) environments. One way ANOVA was used to compare normotensives with hypertensive individuals with and without the use of antihypertensive medications in the WH environment. Unpaired t-tests were used to compare differences between hypertensives and normotensives in the HD environment. No differences in critical environmental limits were observed in either environment among all groups (all p>0.05). These data challenge the hypotheses that hypertension increases heat-related risk. Despite potential alterations in heat loss mechanisms due to hypertension and antihypertensive medications, there were not differences in the compensable environmental conditions in individuals with stage 1 hypertension.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646780","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":"Splicing Factor Kinase SRPK1 inhibition in Monocyte: A Novel Therapeutic Approach for Peripheral Arterial Disease.","authors":"Tohru Fukai, Masuko Ushio-Fukai","doi":"10.1152/ajpheart.00156.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00156.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646783","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}