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

{"title":"The two-pore K⁺ channel TREK-1 regulates pressure overload-induced cardiac remodeling.","authors":"Cemantha M L Johnson, Drew M Nassal, Alexander J Winkle, Benjamin Buck, Xianyao Xu, Xiaoping Wan, Mei Han, Simon Lococo, Nicholas Leahy, Shivangi Mohta, Rebecca Shaheen, Omer Cavus, Aaryan Kohli, Yuanyuan Cao, Mona El Refaey, Sakima Smith, Xun Ai, Isabelle Deschenes, Thomas J Hund","doi":"10.1152/ajpheart.00821.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00821.2024","url":null,"abstract":"<p><p>Heart failure (HF) represents a major burden on the healthcare system with HF patients at increased risk for a host of comorbidities including ventricular arrhythmias. Despite considerable advances in defining cell- and organ-level changes associated with HF, the precise mechanisms driving structural and electrical remodeling remain to be defined. We sought to elucidate the role of the two-pore K⁺ channel TREK-1 in cardiac remodeling in pressure overload-induced HF. Cardiac-specific TREK-1 conditional knockout (TREK1cKO) and floxed control mice were subjected to transaortic contraction (TAC) or sham procedure and evaluated for 6 weeks by echocardiography and sub-surface electrocardiograms. Ventricular myocytes were isolated for action potential, intracellular Ca²⁺, and contractility measurements. The expression/regulation of key cell signaling pathways were evaluated early in remodeling. TREK1cKO and control mice showed a significant decrease in cardiac systolic function with evidence of hypertrophy as early as 2 weeks post-TAC compared to sham. However, TREK1cKO mice displayed a more severe decline in function with enhanced left ventricular chamber dilation (eccentric remodeling) compared to control 6 weeks post-TAC. Similarly, TAC TREK1cKO mice demonstrated greater prolongation of the QT and QRS intervals compared to TAC control. TAC TREK1cKO ventricular myocytes exhibited greater action potential prolongation with paradoxical improvements in Ca²⁺ homeostasis and contractility compared to control. 2 weeks post-TAC, TREK1cKO hearts exhibited elevation of STAT3 phosphorylation at Y705 compared to control. Our findings reveal a complex interaction between chronic stress, TREK-1, STAT3 regulation, and cardiac remodeling, with TREK-1 exerting both maladaptive and protective effects on overall cardiac function.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092276","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":"Women's Cardiovascular Health at Risk: An Urgent Call to Protect the U.S. Biomedical Research System and Prevent Setbacks in Women's Health Research.","authors":"Styliani Goulopoulou, Donna A Santillan, Julia Unternaehrer","doi":"10.1152/ajpheart.00182.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00182.2025","url":null,"abstract":"<p><p>This paper calls on the scientific community and academic institutions to take urgent actions to protect research and infrastructure, ensuring that hard-won gains in understanding sex-specific cardiovascular disease mechanisms are not lost in an already underfunded field. We provide a roadmap with recommended actions and implementation strategies to address challenges and threats to women's cardiovascular health research.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101170","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 Biomarkers in Cardio-Oncology: From Promise to Practice Through Prospective Study.","authors":"Caitlin F Bell, Zachary S Clayton","doi":"10.1152/ajpheart.00338.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00338.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092332","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":"From the Operating Room to the Bench: Use of Reverse Translation to Identify Targets in Aortic Aneurysm.","authors":"Rashi Purohit, Julie K Freed","doi":"10.1152/ajpheart.00304.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00304.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075521","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-Specific Modulation of Cardiac Fibrosis and Lipid Metabolism by B-Vitamins in Heart Failure with Reduced Ejection Fraction in Mice.","authors":"Chloé David, Sonia Deschênes, Gabriel Ichkhan, Caroline Daneault, Isabelle Robillard Frayne, Bertrand Bouchard, Anik Forest, Yan Fen Shi, Marie-Ève Higgins, Martin G Sirois, Jean-Claude Tardif, Mathias Mericskay, Jérôme Piquereau, Matthieu Ruiz","doi":"10.1152/ajpheart.00841.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00841.2024","url":null,"abstract":"<p><p><b>Aims:</b> Despite significant advancements in therapies, heart failure (HF) remains a major health challenge. Women, who are underrepresented in HF research, are particularly in need of effective treatments. B-vitamins are a promising and cost-effective option for improving cardiac function. Our study aimed to investigate the sex-specific effects of B-vitamin supplementation on HF with reduced ejection fraction in mice. <b>Methods and results:</b> Male and female mice underwent transverse aortic constriction (TAC) to induce pressure overload. Four weeks post-TAC, mice were randomized to receive either a standard or a vitamin B-enriched (VitB) diet. We found that in females, but not in males, VitB: i) extended survival, ii) slowed down the decrease in ejection fraction (EF), and iii) improved left ventricular morphology. The observed benefits in females were associated with evidence of improved cardiac and lung fibrosis as well as lower inflammation. In contrast, in males, VitB treatment did not reduce cardiac and lung fibrosis while inflammation remained active in the myocardium. Regarding the circulating lipidome, disturbances were normalized in females with a specific enrichment in long-chain and polyunsaturated triglycerides (TG) in response to VitB. Conversely, in males, lipidomic alterations remained under VitB treatment and were characterized by the accumulation of shorter and saturated TG in the circulation and myocardium. <b>Conclusion:</b> These data reveal a sex-specific response to VitB supplementation in HF in the context of pressure overload and point to a differential lipidomic remodeling that is only favorable in females.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960833","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":"Adding insult to injury - myocardial cell death and dysfunction in donor hearts subjected to warm ischemia.","authors":"Oscar van der Have, Karin Tran-Lundmark","doi":"10.1152/ajpheart.00284.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00284.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956444","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":"Rapamycin Reduces Arterial Mineral Density and Promotes Beneficial Vascular Remodeling in a Murine Model of Severe Medial Arterial Calcification.","authors":"Parya Behzadi, Andrew A Wendling, Rolando A Cuevas, Alex Crane, Claire C Chu, William J Moorhead, Ryan Wong, Mark Brown, Joshua Tamakloe, Swathi Suresh, Payam Salehi, Iris Z Jaffe, Allison L Kuipers, Lyudmila Lukashova, Konstantinos Verdelis, Cynthia St Hilaire","doi":"10.1152/ajpheart.00530.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00530.2024","url":null,"abstract":"<p><p>Peripheral artery disease (PAD) is the narrowing of the arteries that carry blood to the lower extremities. PAD has been traditionally associated with atherosclerosis. However, recent studies have found that thrombotic events triggered by medial arterial calcification (MAC) is the primary cause of chronic limb ischemia below the knee. MAC is localized around the elastic fibers surrounding smooth muscle cells (SMCs) in arteries. Matrix GLA protein (MGP) binds circulating calcium and prevents hydroxyapatite mineral deposition, while also modulating pro-osteogenic signaling by attenuating BMP-2-mediated activation of <i>Runx2</i> gene expression. <i>Mgp^-/-</i> mice develop severe MAC and die around 8 weeks after birth due to aortic rupture or heart failure. We previously discovered a rare genetic disease Arterial Calcification due to Deficiency of CD73 (ACDC), in which patients present with extensive MAC in their lower extremity arteries. Using a patient-specific induced pluripotent stem cell model, we found that rapamycin inhibited calcification. Here we investigated whether rapamycin could reduce MAC in vivo using the <i>Mgp^-/-</i> murine model. <i>Mgp^+/+</i> and <i>Mgp^-/-</i> mice received 5mg/kg rapamycin or vehicle. Calcification content was assessed via microCT, and vascular morphology and extracellular matrix content were assessed histologically. Immunostaining and western blot analysis were used to examine SMC phenotype and extracellular matrix content. Rapamycin prolonged <i>Mgp^-/-</i> mice lifespan, decreased mineral density in the arteries, maintained SMC contractile phenotype, and improved vessel structure, however, calcification volume was unchanged. <i>Mgp^-/-</i> mice with SMC-specific deletion of Raptor or Rictor did not recapitulate treatment with rapamycin. These findings suggest rapamycin promotes beneficial vascular remodeling in vessels with MAC.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962166","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":"Loss of RET-ROS at complex I induces diastolic dysfunction in mice that is reversed by aerobic exercise.","authors":"Ana Vujic, Amy Koo, Guillaume Bidault, Jan Lj Miljkovic, Andrew M James, Andreas Dannhorn, Xiaowen Duan, Lucy M Davis, Jiro Abe, Joyce Valadares, Jordan J Lee, Alexis Diaz-Vegas, Keira Turner, Richard Goodwin, Daniel J Fazakerley, Antonio Vidal Puig, Michael P Murphy, Thomas Krieg","doi":"10.1152/ajpheart.00482.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00482.2024","url":null,"abstract":"<p><p>Central to the development of heart failure with preserved ejection fraction (HFpEF) is the redox disruption of metabolic processes, however, the underlying mechanisms are not fully understood. This study utilized a murine model (ND6) carrying a homoplasmic mitochondrial DNA point mutation (<i>ND6 G13997A</i>), which maintains functional NADH oxidation but lacks the site-specific reactive oxygen species (ROS) generation <i>via</i> reverse electron transport (RET). We demonstrate that mice with RET-ROS deficiency have reduced exercise capacity despite higher lean body mass, impaired resilience to high-fat/high-sucrose dietary stress, and cardiac hypertrophy with diastolic dysfunction. Importantly, dobutamine-induced stress elevated succinate levels in the heart, accompanied by RET-ROS production in WT but not in ND6 mice. Furthermore, ND6 mice showed perturbation in metabolite profiles following dobutamine stress. Mechanistically, the ND6 heart had an upregulated expression of fatty acid transport, oxidation, and synthesis genes (<i>CD36, Cpt1b, Acly, Fas, Elovl6</i> and <i>Scd1</i>) and increased protein levels of lipid metabolism regulators (acetyl-CoA carboxylase and perilipin 2). Interestingly, 8 weeks of forced treadmill running increased acetyl-CoA abundance, alleviated metabolic stress, and improved diastolic function in RET-ROS mutant hearts. In summary, these findings reveal a critical role for RET-ROS in regulating exercise capacity and cardiometabolic health, identifying it as a potentially selective target for modulating cardiac metabolism.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962159","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-specific cardiac electrophysiological remodeling influences the susceptibility to arrhythmias in elderly rats.","authors":"Rosario Statello, Giovanna Pelà, Roberta Maestri, Fabio Leonardi, Aderville Cabassi, Ignazio Verzicco, Alessandra Rossi, Luca Carnevali, Paolo Pastori, Domenico Corradi, Michele Miragoli, Emilio Macchi, Stefano Rossi","doi":"10.1152/ajpheart.00199.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00199.2025","url":null,"abstract":"<p><p>Advanced age is a well-known risk factor for cardiovascular disease (CVD), with sex differences contributing significantly to age-dependent clinical heterogeneity. The incidence of CVD increases with age in both sexes, although men and women are predisposed toward different CVDs. However, the sex-specific arrhythmogenic alterations in aged individuals are still not described in depth. The present work aimed to analyze gross anatomical and relevant cardiac electrophysiological parameters <i>in vivo</i> in aged female and male rats, emphasizing sex-related disparities and their relationship with enhanced arrhythmia vulnerability. Studies were performed on healthy wild-type Groningen rats: 13 adult males (8.2±1.2months), 13 aged males (25.6±0.7months), 13 adult females (9.8±3.2months), and 13 aged females (23.0±1.4months). The adult female heart was hypertrophic compared to adult males, but aging was associated with cardiac hypertrophy only in male rats. Adult female rats had longer effective refractory period and QTc than males, but only male rats showed a significant increase in these parameters with age. Conversely, aged animals showed longer ventricular activation time than adults in both sexes. Although conduction velocity remained consistent across groups, phase map study revealed prolonged activation time in the aged female compared to all other groups. Notably, while aged rats were more prone to spontaneous supraventricular extrasystoles, only aged males were more susceptible to spontaneous ventricular arrhythmias. In conclusion, sex strongly influences the cardiac electrical remodeling, with male that could experience more significant adaptations. Accordingly, when the heart is exposed to proarrhythmic stimuli, the susceptibility to arrhythmias differs between elderly males and females.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952338","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":"Evolving Hemodynamics in Fontan Circulation: Age-Driven Insights in Patients with Interrupted Inferior Vena Cava and Hepatoazygos Shunt.","authors":"Vikas Kannojiya, Akshita Sahni, Emily Eickhoff, Neha Zacharia, Nicole St Clair, Noah Schulz, Peter E Hammer, Pedro J Del Nido, Rahul Rathod, David M Hoganson, Vijay Govindarajan","doi":"10.1152/ajpheart.00072.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00072.2025","url":null,"abstract":"<p><p>Patients with interrupted inferior vena cava (I-IVC) and azygos continuation who undergo Fontan completion via hepatoazygos shunting (HAS) exhibit unique hemodynamic challenges. This study evaluates age-related shifts in systemic venous return dominance, hepatic flow distribution (HFD), power loss (PL), and flow disturbances using patient-specific computational fluid dynamics (CFD). Data analysis from 95 I-IVC patients showed a non-linear shift in upper-to-lower body systemic flow dominance with ratios of 2, 1, and 0.5 (correlating to ages ~3, ~10, and ~20 respectively). CFD simulations for 17 selected patients revealed a trend of increasing HFD toward the right pulmonary artery (RPA), with median splits of 45%-49%, 48%-52%, and 40%-60% for the respective flow ratios. Power loss increased significantly with lower-body flow dominance. Median values for absolute PL were 4.75 mW (ratio 2), 16.5 mW (ratio 1), and 33.7 mW (ratio 0.5). Indexed PL showed a similar trend, rising from 0.04 mW/m² to 0.11 mW/m² across the flow ratios. Vorticity (VOR) and viscous dissipation rates (VDR), key metrics of flow disturbances, also increased with lower-body flow dominance, showing strong correlations with PL (R = 0.58-0.76). Kruskal-Wallis based statistical analysis identified significant statistical differences in absolute PL (p = 0.0045) and flow disturbances (p < 0.001), emphasizing the impact of age-related flow dynamics on Fontan efficiency. Our findings emphasize the need for targeted interventions in patients with I-IVC with azygos continuation to mitigate evolving hemodynamic inefficiencies and optimize Fontan outcomes during critical growth periods.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965405","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}