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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175171/pdf/","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":"OA","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":"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":"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172006/pdf/","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":"OA","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}

{"title":"Parental obesity predisposes male and female offspring to exacerbated cardiac dysfunction and increased mortality after myocardial infarction.","authors":"Jussara M do Carmo, Ana C M Omoto, John E Hall, Xuemei Dai, Emily C Ladnier, Marilia C Mouro, Odecio E S Tosta, Zhen Wang, Xuan Li, Alexandre A da Silva","doi":"10.1152/ajpheart.00827.2024","DOIUrl":"10.1152/ajpheart.00827.2024","url":null,"abstract":"<p><p>Acute myocardial infarction (MI) is a leading cause of death worldwide, accounting for >1 million deaths/year in the United States alone. Although parental obesity is a risk factor for offspring cardiovascular diseases, the impact of parental obesity on offspring outcomes after MI is unknown. This study examined if non-obese male and female offspring from obese Sprague-Dawley rat parents fed a high-fat diet (HFD-Offs, <i>n</i> = 11-19/sex) are at greater risk of death and worse cardiac dysfunction after MI, compared with offspring from lean parents fed a normal diet (ND-Offs, <i>n</i> = 12-15/sex). All offspring were fed ND from weaning and subjected to left descending coronary artery ligation at 12 wk of age to induce MI. Survival rate 24 h post-MI was examined, and cardiac function was measured by echocardiography and intraventricular catheterization with a Millar catheter on <i>day 7</i> post-MI. Compared with ND-Offs, male and female HFD-Offs exhibited increased ventricular fibrillation and reduced survival post-MI (male: 37% vs. 80% and female: 55% vs. 83% for HFD-Offs and ND-Offs, respectively). In surviving rats, systolic dysfunction was more pronounced in male and female HFD-Offs compared with ND-Offs at <i>day 7</i> post-MI, despite similar infarct size in all groups. We also found reductions in baseline O₂ consumption rate and pyruvate-supported mitochondrial respiration, as well as increased mitochondria-derived superoxide production in cardiac fibers from HFD-Offs. Thus, parental obesity is associated with an increased 24-h mortality rate in their offspring after induction of MI and worse systolic function even when the offspring are fed a healthy diet after weaning and remain lean.<b>NEW & NOTEWORTHY</b> A major new finding of this study is that parental obesity markedly reduces survival rate and exacerbates cardiac dysfunction after myocardial infarction in their offspring, and this effect is independent of offspring sex.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1039-H1050"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668897","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":"Carotid artery stiffness mechanisms, heart failure events, and atrial fibrillation in MESA: the Multi-Ethnic Study of Atherosclerosis.","authors":"Ryan Pewowaruk, Claudia E Korcarz, David A Bluemke, Mohamed H Hamdan, Susan R Heckbert, Joao A C Lima, Yacob Tedla, Adam D Gepner","doi":"10.1152/ajpheart.00047.2025","DOIUrl":"10.1152/ajpheart.00047.2025","url":null,"abstract":"<p><p>Arterial stiffness can be separated into two main mechanisms: <i>1</i>) load-dependent stiffening from higher blood pressure and <i>2</i>) structural stiffening due to remodeling of the vessel wall. The relationship of stiffness mechanisms with heart failure (HF) and atrial fibrillation (AF) is unknown. MESA (multi-ethnic study of atherosclerosis) participants with baseline carotid ultrasound images were included in this study (HF <i>n</i> = 6,278; AF <i>n</i> = 5,292). Carotid pulse wave velocity (cPWV) was calculated from B-mode carotid ultrasound to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 mmHg blood pressure with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Associations with incident heart failure events and atrial fibrillation diagnosis were assessed with adjusted Cox hazard models. Four hundred-seven HF events and 1,157 AF diagnoses occurred during a median 17.7 and 16.8 years of follow-up. The associations of carotid artery stiffness mechanisms with HF events were: total cPWV adjusted HR per 1 SD 1.09 [0.98-1.22], <i>P</i> = 0.11; structural cPWV adjusted HR 1.06 [0.94-1.18], <i>P</i> = 0.33; and load-dependent PWV adjusted HR 1.23 [1.05-1.44] per 1 m/s, <i>P</i> = 0.009. The associations of carotid artery stiffness mechanisms with AF diagnoses were: total cPWV adjusted HR 1.11 (1.04-1.20), <i>P</i> = 0.004; structural cPWV adjusted HR 1.10 [1.02-1.16], <i>P</i> = 0.017; load-dependent cPWV adjusted HR 1.12 [1.02-1.23], <i>P</i> = 0.020. Both structural and load-dependent cPWV were associated with the development of AF, and load-dependent cPWV was associated with HF events. These findings indicate that load-dependent cPWV may be a potential treatment target to reduce the incidence of both HF and AF.<b>NEW & NOTEWORTHY</b> We evaluated associations between novel components of arterial stiffness: <i>1</i>) load-dependent stiffening from higher blood pressure and <i>2</i>) structural stiffening due to remodeling of the vessel wall and their associations with incident heart failure (<i>n</i> = 6,278) and atrial fibrillation (<i>n</i> = 5,292) over ∼17 years of follow-up. We found that both baseline structural and load-dependent stiffness were associated with the development of atrial fibrillation and load-dependent stiffness was associated with heart failure events.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1019-H1025"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668895","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":"Oxidative stress and pediatric diabetic cardiovascular complications: emerging research and clinical applications.","authors":"Saman Saedi, Yi Tan, Sara E Watson, Joshua D Sparks, Kupper A Wintergerst, Lu Cai","doi":"10.1152/ajpheart.00673.2024","DOIUrl":"10.1152/ajpheart.00673.2024","url":null,"abstract":"<p><p>The prevalence and incidence of diabetes in pediatrics have dramatically increased over the last three decades. Comparatively, pediatric diabetes has faster pancreatic β-cells decline and early progression to complications compared with adult diabetes. Therefore, diabetic complications are a major concern in children and adolescents with diabetes. Diabetes has detrimental effects on the macro- and microvascular systems, resulting in cardiovascular diseases, leading causes of morbidity and mortality in youth with diabetes. Oxidative stress plays a critical role in developing cardiovascular complications in the context of pediatric diabetes. In pediatric patients with diabetes, several factors can contribute to the development of excess reactive oxygen species and oxidative stress, including nutritional deficiencies, puberty, environmental exposures, and metabolic disorders such as obesity and high blood pressure. The present study aims to raise awareness of diabetic cardiovascular complications in children and adolescents with diabetes and the role of oxidative stress and their molecular mechanisms in the pathogenesis of cardiovascular complications. In addition, some novel therapeutic strategies for the treatment and prevention of diabetic cardiovascular complications in the pediatric populations are highlighted. In summary, children and adolescents with diabetes no matter type 1 diabetes (T1D) or type 1 diabetes (T2D), have many features similar to those in adults with same kinds of diabetes, but also have many their own features distinct from adults. By developing targeted therapies and preventive measures, healthcare providers can better address the rising incidence of diabetes-related complications in children and adolescents.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H945-H962"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522456","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}