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

{"title":"Elevated maternal cholesterol is linked to a coexpression network of neonatal indole metabolism and birth weight.","authors":"Lik Hang Wu, Jielin Yang, Leroy Sivappiragasam Pakkiri, Lara J Monteiro, Reyna Peñailillo, Poh Leong Lim, Mahesh A Choolani, Matthew W Kemp, Ling-Jun Li, Claudette Cantin, Ignacio Valenzuela, Andrea Leiva, Chester Lee Drum, Sebastián E Illanes","doi":"10.1152/ajpheart.00854.2025","DOIUrl":"10.1152/ajpheart.00854.2025","url":null,"abstract":"<p><p>The developmental origins of health and disease (DOHaD) hypothesis links intrauterine exposure to suboptimal fetal development and later-life cardiometabolic health. In 56 mother-newborn pairs, we quantified 389 newborn cord blood metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and recorded 24 clinical variables. With weighted coexpression network analysis, we identified <i>module 05</i>, comprising birth weight and metabolites enriched for the \"gut-liver indole metabolism\" pathway (indole, indole-3-pyruvic acid, and indole-3-lactic acid). Multivariable regression revealed that each 1-SD higher <i>module 05</i> expression score was associated with -0.26 [95% confidence interval (CI): -0.51, -0.01]-SD lower 3rd-trimester total cholesterol (<i>P</i> = 0.039), adjusting for newborn and maternal covariates. This supports a coordinated newborn pattern of lower birth weight and lower cord blood indole metabolite abundance in pregnancy cases with higher late-pregnancy total cholesterol. Stratified analyses further suggested that, among pregnancies with maternal supraphysiological hypercholesterolemia (MSPH; 3rd-trimester total cholesterol ≥ 280 mg/dL), higher maternal age and higher 1st-trimester systolic blood pressure were accompanied by lower <i>module 05</i> score, whereas these associations were not observed in non-MSPH pregnancies. Complementary regression analysis associated each tertile higher cord blood indole-3-propionic acid (IPA) with -9.09 [-17.45, -0.72]-mg/dL lower 1st-trimester cholesterol (<i>P</i> = 0.038). Separately, each 1-tertile higher IPA was linked to 192.22 [55.44, 329.00]-g higher newborn weight (<i>P</i> = 0.008). Both 1st- and 3rd-trimester total cholesterols were positively associated with higher cord blood oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG). In conclusion, maternal cholesterol level varies with cord blood indole metabolites and birth weight, suggesting a potential shared metabolic axis modifiable by maternal cholesterol level in mother-newborn pairs.<b>NEW & NOTEWORTHY</b> This study identifies a coexpression network module connecting birth weight with cord blood indole metabolites, highlighting an integrated neonatal growth-metabolism signature. Maternal lipid status tracks with this signature, adding molecular resolution to the developmental origins of health and disease (DOHaD) paradigm by implicating growth-linked biochemical perturbations in gut-derived indole metabolites. Given the established relevance of indole metabolites to cardiovascular health, our preliminary results motivate future studies aimed at targeting neonatal metabolism as an early window for cardiovascular health intervention.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1405-H1419"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497289","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 Medium Chain Fatty Acid Octanoate is a Beneficial Fuel for the Failing Heart.","authors":"Nikoloz Gorgodze, Timothy R Matsuura, Noemi Nisini, Remus Berretta, Alessandra Recchia, Alisha Werlen, Tao Wang, Kirill Batmanov, Steven Houser, Daniel P Kelly, Fabio A Recchia","doi":"10.1152/ajpheart.00153.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.00153.2026","url":null,"abstract":"<p><p>The failing heart displays marked alterations of energy substrate metabolism, with a reduced oxidation of long chain fatty acids (FA) associated with increased glucose oxidation. Recent pre-clinical and human studies have shown that the delivery of ketone bodies as an alternative substrate reduces pathologic cardiac remodeling and dysfunction in heart failure. However, chronic administration of ketone bodies is challenging. Therefore, using a clinically relevant canine model of tachypacing-induced dilated cardiomyopathy, we tested the hypothesis that other shorter chain FA may also be beneficial. Seven dogs received cardiac tachypacing and continuous infusion of sodium octanoate, a medium-chain FA, starting after 2 weeks of pacing when cardiac dysfunction was still moderate. Six dogs received cardiac pacing with no octanoate infusion. Octanoate did not significantly alter circulating levels of ketone bodies, while it still exerted protection resulting in a delayed progression of systolic and diastolic cardiac dysfunction and normalized myocardial metabolism. These results identify the delivery of medium-chain FA as a potential actionable therapeutic for heart failure with reduced ejection fraction. Octanoate has translational promise due to proven methods of dietary supplementation with no need for parenteral administration.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759995","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":"Myeloid transglutaminase 2 regulates Treg-Th17 balance in a female model of Angiotensin II-induced hypertension and vascular stiffening.","authors":"Huma Naz, Emma Teixeiro, Camila Manrique-Acevedo, Guido Lastra","doi":"10.1152/ajpheart.00095.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.00095.2026","url":null,"abstract":"<p><p>Hypertension and arterial stiffening are major contributors to cardiovascular disease and are closely linked to vascular inflammation. Activation of the renin-angiotensin-aldosterone system promotes unfavorable immune responses that lead to vascular inflammation and remodeling; however, the exact molecular mediators connecting immune activation to arterial stiffening remain poorly understood. Transglutaminase 2 (TG2) is a multifunctional enzyme involved in extracellular matrix remodeling and inflammatory signaling, expressed in both vascular and immune cells. We hypothesized that TG2 in myeloid cells facilitates Angiotensin II (Ang II)-induced hypertension and aortic stiffening by driving detrimental immune responses. Female mice with myeloid-specific deletion of TG2 (MyTG2KO) and littermate controls were infused with Ang II for 14 days. Ang II infusion resulted in elevated systolic blood pressure, aortic stiffness, and vascular collagen deposition in control mice, whereas these responses were markedly reduced in MyTG2KO mice. Deleting myeloid TG2 lowered vascular expression of proinflammatory markers and circulating cytokines. Flow cytometry analysis showed that Ang II was associated with disruption of immune balance, characterized by decreased regulatory T cells (Tregs) and increased Th17 cells; these changes were attenuated in MyTG2KO mice. Consistent with these results, TG2-deficient macrophages promoted Treg development, suppressed Th17 polarization, and decreased CD8⁺T cell cytotoxicity in co-culture experiments. These findings highlight myeloid TG2 as an important contributor to Ang II-related immune imbalance, vascular inflammation, aortic stiffening, and hypertension. Targeting TG2 in myeloid cells could be a novel strategy to reduce immune-driven vascular remodeling in hypertensive cardiovascular disease.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760045","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":"Parental obesity exacerbates cognitive dysfunction and cardiac vulnerability in offspring of an Alzheimer disease model.","authors":"Jussara M do Carmo, John E Hall, Emily Ladnier, Xuemei Dai, Zhen Wang, Alan J Mouton, Ana C M Omoto, Luciana Jorge, Alexandre A da Silva","doi":"10.1152/ajpheart.00047.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.00047.2026","url":null,"abstract":"<p><p>Alzheimer disease (AD) is a growing health problem characterized by neurocognitive and cardiovascular dysfunction. Although parental obesity programs adverse cardiometabolic complications, including obesity, hypertension and cardiorenal dysfunction in their offspring, whether parental obesity worsens cardiac, metabolic, and cognitive function in lean offspring that are susceptible to AD (3xTg-AD mice) remains unclear. Male and female offspring from control diet-fed or high fat diet (HFD)-fed parents were examined at 26-28 weeks of age. Cognitive function was assessed by Morris Water Maze and New Object Recognition (NOR) tests, cardiac function by echocardiography and invasive hemodynamic measurements, and mitochondrial (MT) function by high-resolution respirometry in isolated cardiac fibers and brain cortex. AD offspring from obese parents (HFD-Offs) exhibited worse memory retention compared to AD offspring from lean parents (ND-Offs), whereas recognition memory assessed by NOR was not significantly different between groups although there was greater variability in HFD-Offs. Although systolic function by echocardiography was similar between groups, male HFD-Offs showed impaired diastolic relaxation with prolonged isovolumetric relaxation time (IVRT), while E/e' remained unchanged. Left ventricular catheterization showed reduced indices of contractility and relaxation, including maximal and minimal rates of pressure changes: dP/dtmax (8,038±1011 vs. 18,704±183 mmHg/sec), dP/dtmin (-7,724±471 vs. -13,634±1139) and prolonged Tau (4.0±0.1 vs. 2.9±0.1) in HFD-Offs compared to ND-Offs. Male HFD-Offs exhibited reduced MT glucose and fatty acid oxidation in heart and brain. These findings indicate that parental obesity exacerbates AD-related cognitive decline and cardiac dysfunction in a sex-specific manner, suggesting parental metabolic status as an important determinant of AD-related cardiometabolic vulnerability.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759987","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":"Beyond the Agatston Score: Unmasking the Metabolic and Cellular Imprint of Coronary Artery Calcification in Postmenopausal Women.","authors":"Sarah Pribil Pardun, Spencer Duff, Lie Gao","doi":"10.1152/ajpheart.00315.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.00315.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760009","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":"Inflammation-Autonomic Crosstalk Contributes to Left Ventricular Diastolic Dysfunction in Type 2 Diabetes: A Rationale for Neuromodulation.","authors":"Nuwani Wijesooriya, Senali Silva, Dulani Kottahachchi, Nadisha Badanasinghe, Dinu S Chandran, Yugeesh R Lankadeva, Tania Warnakulasuriya","doi":"10.1152/ajpheart.01006.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.01006.2025","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a globally prevalent metabolic disorder frequently complicated by cardiovascular pathologies, notably left ventricular diastolic dysfunction (LVDD), which can progress to heart failure with preserved ejection fraction (HFpEF). There is emerging evidence of a crucial interplay between autonomic dysfunction and chronic low-grade inflammation in the pathogenesis of LVDD in T2DM patients. The bidirectional crosstalk between the autonomic nervous system and the immune system has been a novel area explored in preclinical studies. Autonomic dysfunction, as evidenced by reduced heart rate variability and impaired baroreflex sensitivity, is common among patients with T2DM. The interaction between the autonomic nervous system and inflammation is altered in T2DM, shifting towards vagal withdrawal and the release of pro-inflammatory cytokines (e.g., TNF-α, IL1β, IL-6, and TGF-β), which can promote myocardial stiffening and fibrosis. These pathophysiological mechanisms, together with metabolic and hemodynamic dysfunction in T2DM, can lead to HFpEF. Neuromodulation techniques, such as vagal nerve stimulation, have shown promise in reducing myocardial fibrosis and HFpEF in preclinical studies. Vagal nerve stimulation is thought to dampen the pro-inflammatory responses, thereby promoting tissue repair and protecting against cardiac dysfunction. In this review, we explore how inflammation-autonomic crosstalk represents a pivotal mechanism in the development of LVDD in T2DM, providing a scientific rationale for neuro-modulatory interventions.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760047","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":"Stress, Behavior, and Cardiovascular Disease: Is Physical Activity a Missing Link?","authors":"Han Le, Amadou Gaye","doi":"10.1152/ajpheart.00241.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.00241.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759956","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 Bump to Pump: Extracellular Matrix Remodeling, Dynamics, and Biomechanics in the Maternal Heart.","authors":"Avery N Kendall, Iona M A Palmer, Helen E Collins","doi":"10.1152/ajpheart.00917.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00917.2025","url":null,"abstract":"<p><p>Although a large percentage of pregnancy-related morbidity and mortality is the result of cardiovascular diseases, little is known about the underlying mechanisms that contribute to the development of adverse cardiac changes during pregnancy. It is clear that during pregnancy, the heart adapts to increased ventricular preload through the development of a reversible, pregnancy-induced cardiac hypertrophy. Cardiomyocyte growth must be supported by changes in the cardiac extracellular matrix (ECM), an extremely diverse and dynamic set of components, whose composition and regulation affect cardiac biomechanics. The ECM undergoes extensive remodeling during periods of cardiac stress, such as those experienced during pregnancy and the postpartum period; however, the full extent of ECM changes and their contributions to biomechanical changes and maternal heart plasticity remain vastly understudied. Recent studies suggest alterations in the expression of several fibrillar collagens, such as collagens I and III, and regulatory proteins, such as matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases, occur during a healthy pregnancy. On the contrary, in the setting of pregnancy-associated cardiovascular diseases, such as preeclampsia and peripartum cardiomyopathy, adverse changes in ECM remodeling have been reported. This review aims to summarize the current state of the field highlighting changes in the cardiac ECM and its components during healthy pregnancies, how perturbations in ECM remodeling can lead to the development of pregnancy-related cardiovascular pathologies, and discuss the notable gaps in knowledge that need to be addressed if we are to fully understand ventricular remodeling in the context of pregnancy and reduce maternal cardiovascular disease burden.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760049","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":"Who was the catalyst for doubling of NIH funding in the late 1990s? Maybe we should thank Senator Tom Daschle.","authors":"A Martin Gerdes","doi":"10.1152/ajpheart.00119.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.00119.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759976","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":"Aging and DNA damage are associated with the development of endothelial cell clonal expansion.","authors":"Hossein Abdeahad, Denisse G Moreno, Arthur Jose Pontes Oliveira de Almeida, Larisse Virgolino da Silva Pontes, Lisa A Lesniewski, Anthony J Donato","doi":"10.1152/ajpheart.00102.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.00102.2026","url":null,"abstract":"<p><p><b>Background:</b> Endothelial dysfunction is a hallmark of vascular aging and a key contributor to cardiovascular disease. While senescence has been widely studied as a terminal endothelial cell fate, recent evidence suggests that clonal expansion, the proliferative expansion of genetically identical cells, may also occur in aged tissues. <b>Objective:</b> We sought to determine whether endothelial clonal expansion increases with age, specifically at the atheroprone regions of the aorta, and to evaluate whether DNA damage promotes endothelial cell clonal expansion. <b>Methods:</b> Tamoxifen-inducible, endothelial-specific confetti-Vecad male and female mice were used to quantify clonal expansion in endothelial cells (ECs) across the aortic region in both young (4 months) and aged (24 months) mice. We further examined the effect of DNA damage by administering systemic DOXO to assess clonal dynamics in different aortic regions. <b>Results:</b> Aging significantly increased EC clone size and the percentage of clonal ECs in atheroprone regions, particularly the minor arch, while only clone size increased in non-atheroprone regions. Systemic DOXO administration increased clone size across the aortic region without altering clonal recruitment, indicating selective amplification of pre-existing clones. <b>Conclusion:</b> These findings suggest that clonal expansion is promoted by both aging and DNA damage. Clonal expansion may represent an underrecognized mechanism contributing to endothelial homogeneity and vascular remodeling during aging and in response to sub-lethal genomic stress.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760011","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}