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

{"title":"TREM2 as a regulator of obesity-induced cardiac remodeling: mechanisms and therapeutic insights.","authors":"Eunhee Chung, David Zhang, Maria Gonzalez Porras, Chia George Hsu","doi":"10.1152/ajpheart.00075.2025","DOIUrl":"10.1152/ajpheart.00075.2025","url":null,"abstract":"<p><p>Obesity and type 2 diabetes mellitus (T2DM) are global health challenges that significantly increase the risk of cardiovascular diseases (CVD). Advances in immunometabolism have identified triggering receptor expressed on myeloid cells 2 (TREM2) as a key regulator of macrophage function, lipid metabolism, and inflammation resolution. Although extensively studied in neurodegenerative diseases, TREM2's role in metabolic disorders and cardiovascular health is an emerging area of research. This review explores TREM2's molecular structure and functions, emphasizing its contributions to immunometabolic regulation in obesity and T2DM. Evidence from preclinical models demonstrates that TREM2 modulates macrophage-driven inflammatory responses, lipid clearance, plaque stability, fibrosis, and myocardial remodeling. Translational findings suggest that TREM2 expression correlates with cardiometabolic outcomes, underscoring its potential as a therapeutic target. Key knowledge gaps include TREM2's temporal dynamics during disease progression, sex-specific effects, and interactions with recruited or resident macrophage activation in obesity and T2DM. Integrating mechanistic and translational insights is critical to harness TREM2's immunoregulatory potential for improving CVD outcomes in metabolic disorders.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1073-H1082"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727483","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":"Ventriculo-arterial coupling in pulmonary regurgitation following transannular patch repair of pulmonary stenosis.","authors":"Rahi S Alipour Symakani, Wouter J van Genuchten, Lotte M Zandbergen, Alexander Hirsch, Piotr Wielopolski, Thierry Bové, Yannick J H J Taverne, Willem A Helbing, Beatrijs Bartelds, Daphne Merkus","doi":"10.1152/ajpheart.00614.2024","DOIUrl":"10.1152/ajpheart.00614.2024","url":null,"abstract":"<p><p>Pulmonary regurgitation is a common consequence following the repair of tetralogy of Fallot and can lead to heart failure. Early detection of right ventricular dysfunction remains challenging, and current clinical markers have limited predictive value to identify which patients are at risk for heart failure and require interventions. This study aimed to investigate the potential of ventriculo-arterial coupling as a marker of early right ventricular dysfunction in a porcine model of chronic pulmonary regurgitation following transannular patch repair of neonatal pulmonary stenosis. Neonatal swine were subjected to pulmonary artery banding for 1 mo to induce right ventricular (RV) pressure overload, followed by transannular patch repair (rTAP, <i>n</i> = 10) to create chronic pulmonary regurgitation, and were compared with Sham animals (<i>n</i> = 6). Longitudinal hemodynamic assessments, including pressure-volume analysis and cardiac magnetic resonance imaging, were performed. Ventriculo-arterial coupling (VAC) was defined as the ratio of end-systolic elastance to effective arterial elastance. Over the follow-up period of 4 mo, VAC was preserved in the rTAP group. Effective arterial elastance was significantly lower in rTAP animals (<i>P</i> = 0.001), whereas end-systolic elastance remained unchanged. Lower end-diastolic pulmonary artery pressures and increased early systolic ejection were observed in rTAP, correlating with higher VAC. Ventriculo-arterial coupling remains preserved in chronic pulmonary regurgitation due to decreased afterload, making it unsuitable as an early marker for right ventricular dysfunction. Low afterload, a consequence of diastolic emptying of the pulmonary artery into the right ventricle, may pseudo-normalize systolic function. Alternative markers, for example, focusing on diastolic function and atrio-ventricular interactions should be investigated.<b>NEW & NOTEWORTHY</b> We used a porcine model of sequential loading with pulmonary artery banding and transannular patch mimicking tetralogy of Fallot to test ventriculo-arterial coupling as a marker of early right ventricular dysfunction. Ventriculo-arterial coupling is preserved despite right ventricular dysfunction and afterload is decreased. Pulmonary regurgitation results in low afterload following pulmonary artery pressure drop during diastole. Early systolic ejection is increased and correlates with ventriculo-arterial coupling.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1054-H1064"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646808","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":"Overexpression of adipose tissue ERα enhances PVAT anticontractility via NOX4-derived H₂O₂ and is protective against high-fat diet-induced dysfunction.","authors":"Tiago J Costa, Milene T Fontes, Paula R Barros, Marion C Hope, R Clinton Webb, Camilla F Wenceslau, Reilly T Enos, Cameron G McCarthy","doi":"10.1152/ajpheart.00180.2025","DOIUrl":"10.1152/ajpheart.00180.2025","url":null,"abstract":"<p><p>Menopause has unequivocally been associated with cardiovascular risk and obesity. Loss of estrogen bioavailability is a hallmark of menopause. Estrogen is generally considered vasculoprotective, with estrogen receptor α (ERα) being the predominant receptor subtype that mediates these positive effects. Similarly, estrogen and ERα are known to stimulate white adipose tissue metabolism. However, it is unknown whether ERα could exert a beneficial effect on mesenteric perivascular adipose tissue (PVAT). PVAT is a heterogeneous tissue that surrounds most peripheral blood vessels. In physiological conditions, PVAT has an anticontractile effect on the vasculature. However, in several diseases, PVAT switches its phenotype to become procontractile. To date, the role of ERα in PVAT function in health and disease is unknown. Therefore, we hypothesized that overexpression of adipose tissue ERα (ERα^OE) would <i>1</i>) increase the anticontractile effect of PVAT in chow diet conditions and <i>2</i>) protect mice against a high-fat diet (HFD)-induced PVAT dysfunction. To test this hypothesis, mesenteric resistance arteries, with and without PVAT, were isolated from female ERα^OE mice, which had either been on a regular chow diet or an HFD for 19 wk. We observed that ERα^OE amplifies the anticontractile effect of mesenteric PVAT via NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H₂O₂) in chow conditions, and ERα^OE is protective against a dysfunctional PVAT that is observed after an HFD, via the same anticontractile mechanism. Collectively, these data demonstrate that ERα is vasculoprotective in the context of PVAT. Harnessing this signaling could be important for reducing cardiovascular risk in postmenopausal women.<b>NEW & NOTEWORTHY</b> We have revealed for the first time that overexpression of adipose tissue estrogen receptor α (ERα^OE) amplifies the anticontractile effect of mesenteric PVAT via the biosynthesis of NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H₂O₂), and this overexpression is protective against HFD-induced PVAT dysfunction. Collectively, these data demonstrate an important mechanism by which ERα signaling is vasculoprotective in the context of PVAT.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1065-H1072"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699413","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":"Mitochondrial dynamics: deciphering the role of HDL-C in regulating mitochondrial function and fatty acid oxidation in human skeletal muscle.","authors":"Mauricio Castro-Sepúlveda, Francesca Amati","doi":"10.1152/ajpheart.00219.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00219.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"328 5","pages":"H1087-H1088"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959906","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":"Extracellular matrix cues regulate cardiac pacemaker cell induction from ventricular myocytes.","authors":"Ernest Ngou, Kyoung-Han Kim, Wenbin Liang","doi":"10.1152/ajpheart.00217.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00217.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"328 5","pages":"H1144-H1145"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962178","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":"Cardiac energy metabolism in diabetes: emerging therapeutic targets and clinical implications.","authors":"Archee Panwar, Sufyan O Malik, Muhtasim Adib, Gary D Lopaschuk","doi":"10.1152/ajpheart.00615.2024","DOIUrl":"10.1152/ajpheart.00615.2024","url":null,"abstract":"<p><p>Patients with diabetes are at an increased risk for developing diabetic cardiomyopathy and other cardiovascular complications. Alterations in cardiac energy metabolism in patients with diabetes, including an increase in mitochondrial fatty acid oxidation and a decrease in glucose oxidation, are important contributing factors to this increase in cardiovascular disease. A switch from glucose oxidation to fatty acid oxidation not only decreases cardiac efficiency due to increased oxygen consumption but it can also increase reactive oxygen species production, increase lipotoxicity, and redirect glucose into other metabolic pathways that, combined, can lead to heart dysfunction. Currently, there is a lack of therapeutics available to treat diabetes-induced heart failure that specifically target cardiac energy metabolism. However, it is becoming apparent that part of the benefit of existing agents such as GLP-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors may be related to their effects on cardiac energy metabolism. In addition, direct approaches aimed at inhibiting cardiac fatty acid oxidation or increasing glucose oxidation hold future promise as potential therapeutic approaches to treat diabetes-induced cardiovascular disease.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1089-H1112"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794412","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":"Transport across the thoracic aortic wall: implications for aneurysm pathobiology, diagnosis, and treatment.","authors":"Keshav A Kailash, Shamimur R Akanda, Alexandra L Davis, Christie L Crandall, Mohamed S Zaghloul, Lori A Setton, Carmen M Halabi, Mohamed A Zayed, Jessica E Wagenseil","doi":"10.1152/ajpheart.00886.2024","DOIUrl":"10.1152/ajpheart.00886.2024","url":null,"abstract":"<p><p>Thoracic aortic aneurysms (TAAs) are a dilation of the aorta that may fatally dissect or rupture. The current clinical management for TAA is continuous monitoring and surgical replacement once the aortic diameter reaches a specified size or rate of growth. Although operative intervention is often successful in preventing fatal outcomes, not all patients will reach surgical criteria before an aortic event, and the surgery carries significant risk with a potential requirement for reoperation. There is a need for patient-specific diagnostic tools and/or novel therapeutics to treat TAA. In this review, we discuss fluid and solute transport through the aortic wall (transmural aortic transport), its potential contributions to TAA progression, and possible applications for diagnosis and treatment. We first discuss the structural organization of the aortic wall with a focus on cellular and extracellular matrix (ECM) changes associated with TAA that may alter transmural transport. We then focus on aortic transmural transport processes defined with biphasic and multiphasic theory. Biphasic theory describes fluid interactions with a porous solid (i.e., the aortic wall), whereas multiphasic theory describes fluid and solute(s) interactions with a porous solid. We summarize experimental and computational methods to quantify transport through the aortic wall. Finally, we discuss how transmural transport may be used to diagnose, monitor, or treat TAA. Further understanding of transmural transport may lead to new insights into TAA pathobiology and future clinical solutions.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1113-H1129"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794416","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":"Deficiency of fibroblast growth factor 2 promotes contractile phenotype of pericytes in ascending thoracic aortic aneurysm.","authors":"Weijian Huang, Jennifer C Hill, Sakshi Patel, Tara D Richards, Ibrahim Sultan, David J Kaczorowski, Julie A Phillippi","doi":"10.1152/ajpheart.00834.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00834.2024","url":null,"abstract":"<p><p>Pericytes exhibit progenitor cell-like qualities and associate with the vasa vasorum-vital microvessels nourishing larger arteries and veins. How pericytes change in human ascending thoracic aortic aneurysm (ATAA) remains unknown. Here, we used the public single-nuclei sequencing data to reveal a contractile phenotype transition of pericytes in human ATAA specimens. In addition, we found that a protective factor, fibroblast growth factor 2 (FGF2), is decreased in the aortic adventitia of both male and female patients with ATAA and impacts pericytes. We demonstrated that FGF2 maintained pericytes in a less contractile and high angiogenic phenotype via MAPK and PI3K-AKT signaling pathways. These findings suggested the latent engagement of pericytes in ATAA, providing insights that could guide the development of new therapies against aortic disease.<b>NEW & NOTEWORTHY</b> Here, we revealed that pericytes transition into a contractile phenotype in human ATAA. We demonstrated that FGF2 maintained pericytes in a less contractile and high angiogenic stage via MAPK and PI3K-AKT signaling pathway, whereas we found FGF2 is decreased in the aortic adventitia of patients with ATAA. Our findings suggest how growth factor deficiency in the microenvironment affects pericytes during ATAA, offering leads for potential new therapies for aortic diseases.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"328 5","pages":"H1130-H1143"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965339","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":"Insights into the effect of pre- and postnatal nicotine exposure on cardiovascular development and function.","authors":"Benjamin Rodriguez, Ashton Oliver, Han Le, Chanel Harris, Andrea G Marshall, Pamela Martin, Amadou Gaye, Lori Banks, Antentor Hinton","doi":"10.1152/ajpheart.00768.2024","DOIUrl":"10.1152/ajpheart.00768.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1051-H1053"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456529","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":"X's, Y's, and vascular ties: exploring the role of sex chromosomes in arterial stiffness and vascular aging.","authors":"Zachary S Clayton, Kerrie L Moreau","doi":"10.1152/ajpheart.00130.2025","DOIUrl":"10.1152/ajpheart.00130.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"328 5","pages":"H1083-H1085"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061944","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}