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

{"title":"Cardiac Adaptation in a Murine Iliac Arteriovenous Fistula Model and the Impact of Sex and N-Acetylcysteine Supplementation.","authors":"Erik M Anderson, Victoria R Palzkill, Kyoungrae Kim, Brian Fazzone, Eric M Kunz, Qiongyao Hu, Yong He, Kerri A O'Malley, Scott A Berceli, Terence E Ryan, Salvatore T Scali","doi":"10.1152/ajpheart.90253.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.90253.2026","url":null,"abstract":"<p><p>Hemodialysis arteriovenous fistulas(AVFs) promote left ventricular(LV) hypertrophy, a known predictor of cardiovascular mortality in patients with chronic kidney disease(CKD). AVF flow dynamics do not reliably predict cardiac remodeling suggesting additional causal biological determinants. Sex influences AVF maturation but its role in myocardial adaptation is unknown. We previously demonstrated sex-dependent protective effects of N-acetylcysteine(NAC) on skeletal muscle in a murine iliac AVF model. This study sought to evaluate whether iliac AVF creation produces compensated cardiac hypertrophy, investigate sex as a modifier of cardiac myocyte mitochondrial adaptation, and test NAC supplementation as a therapeutic strategy. Male and female C57BL/6J mice with adenine-induced CKD underwent iliac AVF or sham surgery with saline or NAC treatment. Ultrasound, echocardiography, and cardiac myocyte mitochondrial respiratory testing were performed. AVF creation produced significant aortic flow increases and corresponding diameter growth(male +64%, female +109%, p<0.001). Heart weight increased ~30-40mg over sham for both sexes(p<0.001). Female AVF mice demonstrated higher ejection fraction(94.8±5.1% vs. male-83.1±7.5%, p<0.001) and attenuated diastolic volume increase(32.8±11.8μl vs. 46.5±15.1μl, p=0.003). AVF inflow did not correlate with LV mass or ejection fraction. Cardiac mitochondrial oxidative phosphorylation(OXPHOS) was higher in female AVF mice(sex-effect p=0.01). NAC did not alter cardiac structure or function. Murine iliac AVF creation results in compensated cardiac hypertrophy without heart failure replicating observations documented in patients. Female AVF mice demonstrated greater cardiomyocyte size and respiratory function, plus exaggerated systolic function and minimized dilated cardiomyopathy, supporting sex as a modifier of the compensated cardiac response after AVF creation. NAC was not protective against maladaptive cardiac remodeling or function.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102959","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 gut to heart: the emerging role of dietary fermentable fiber in heart failure with preserved ejection fraction.","authors":"Faisal Darbar, Medha Priyadarshini, Yueyang Wang, Zainab Safdary, Abeer M Mahmoud, Robert J DiDomenico, Paola C Rosas","doi":"10.1152/ajpheart.00177.2026","DOIUrl":"10.1152/ajpheart.00177.2026","url":null,"abstract":"<p><p>Heart failure with preserved ejection fraction (HFpEF) is a multisystemic syndrome that accounts for more than half of all heart failure cases and causes a substantial burden of morbidity and mortality. In contrast to heart failure with reduced ejection fraction, few disease-modifying therapies exist for HFpEF, reflecting differences in pathophysiology. Low fermentable fiber (FF) intake, gut dysbiosis, and depletion of short-chain fatty acids (SCFAs), microbial metabolites central to immune, metabolic, and vascular homeostasis, are increasingly linked to the pathophysiology of HFpEF. Here, we synthesize preclinical and clinical evidence on FF and SCFAs and evaluate their therapeutic relevance to HFpEF. Preclinical studies demonstrate that FF supplementation or direct SCFA administration improves cardiometabolic function and attenuates cardiac remodeling through SCFA receptor signaling, enhanced nitric oxide bioavailability, reduced inflammation, and metabolic support of the energy-starved failing heart. Supporting the translational relevance of these findings, a systematic review of 27 human randomized controlled trials showed that FF interventions exert microbiome-mediated effects, enriching SCFA-producing taxa and augmenting fecal and circulating SCFA levels, while improving insulin sensitivity and reducing abdominal adiposity and low-density lipoprotein cholesterol. Direct SCFA supplementation increases SCFA availability and provides modest metabolic benefits, including reduced adiposity and liver fat. However, its effects are inconsistent. Collectively, these findings provide a mechanistic and translational rationale for FF-based interventions in HFpEF. To date, no clinical trials have evaluated the effects of FF on HFpEF-specific outcomes. Clinical studies are therefore needed to determine whether increasing FF intake can improve symptoms, cardiac function, and disease progression in HFpEF.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1277-H1296"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683216","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":"Lessons from a cardiomyopathy model that didn't fail.","authors":"Khaja Shameem Mohammed Abdul, Nicole H Purcell","doi":"10.1152/ajpheart.90031.2026","DOIUrl":"10.1152/ajpheart.90031.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1377-H1379"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954647","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":"When ventricular load outruns atrial reserve.","authors":"Kipp William Johnson, Anna Pfenniger","doi":"10.1152/ajpheart.90032.2026","DOIUrl":"10.1152/ajpheart.90032.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1212-H1213"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954618","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":"Ventricular-arterial coupling during exercise and tilt assessed using a pulse wave velocity-to-global longitudinal strain ratio.","authors":"Skye H T Ling, Lea Nguyen, Jessica N Jasiak, Jason S Au","doi":"10.1152/ajpheart.00393.2026","DOIUrl":"10.1152/ajpheart.00393.2026","url":null,"abstract":"<p><p>Ventricular-arterial coupling (VAC) is commonly assessed using the echocardiography-derived ratio of arterial elastance to end-systolic elastance (E_a/E_es), a convenient but global construct that collapses ventricular and arterial properties into a single lumped parameter. A proposed index, combining pulse wave velocity and global longitudinal strain (PWV/GLS), provides a mechanistically grounded representation of coupling by directly integrating measures of arterial stiffness and myocardial deformation. This study compared the ability of E_a/E_es and PWV/GLS to discriminate between acute physiological stress conditions. Twenty healthy young adults (10 females; 23 ± 2 yr) completed a randomized crossover-graded cycling protocol (25 and 75 W; fixed heart rate ∼130 beats/min) in supine and 20° head-up tilt (HUT). HUT induces changes in ventricular volume loading, thereby challenging inherent assumptions underlying E_a/E_es. E_a/E_es progressively declined with increasing exercise intensity (main effect of stage <i>P</i> < 0.01; all <i>P</i> < 0.05 from previous stage), reflecting increased left ventricular elastance (E_es) relative to arterial load (E_a). E_a/E_es showed no detectable differences between supine and HUT either at rest or at any exercise stage (interaction <i>P</i> > 0.05). In contrast, PWV/GLS was less sensitive to exercise intensity (all stages only different from baseline <i>P</i> < 0.05) but showed a difference from supine to HUT at rest (<i>P</i> < 0.01). These findings support a context-dependent approach to VAC assessment: E_a/E_es reflects volumetric-pressure coupling during exercise, whereas PWV/GLS was responsive to fluid shifts and preload changes, supporting its potential as an alternative VAC measure that captures arterial wave propagation and myocardial deformation when the assumption of a negligible volume intercept (V₀) is challenged.<b>NEW & NOTEWORTHY</b> This study evaluates ventricular-arterial coupling using traditional E_a/E_es and a novel pulse wave velocity/global longitudinal strain (PWV/GLS) ratio during exercise and head-up tilt. E_a/E_es decreased with graded exercise but was insensitive to postural stress. In contrast, PWV/GLS detected tilt-related changes at rest but showed dampened responsiveness to exercise intensity. These findings demonstrate complementary, context-dependent behavior of coupling metrics and support investigating alternative noninvasive methods to better resolve coupling under dynamic physiological conditions in healthy adults.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1252-H1261"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910617","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":"Evidence for an inflammatory contribution to cutaneous microvascular endothelial dysfunction in non-Hispanic Black women.","authors":"Virginia G Content, Auni C Williams, Lacy M Alexander","doi":"10.1152/ajpheart.00615.2026","DOIUrl":"10.1152/ajpheart.00615.2026","url":null,"abstract":"<p><p>Non-Hispanic Black (NHB) adults demonstrate impaired microvascular endothelial function, characterized as reduced nitric oxide (NO)-mediated vasodilation, compared to non-Hispanic White adults. A sexual dimorphism exists, where microvascular dysfunction is mediated through elevated superoxide generation in NHB men but not NHB women. Inflammatory mechanisms in NHB women may contribute, but these mechanisms have not been explored in vivo. We hypothesized that micro- and macrovascular function would improve after oral salsalate [nuclear factor kappa B (NF-κB) activation inhibitor] in NHB women. After placebo or salsalate (1,500 mg twice a day, 5 days), two intradermal microdialysis fibers were placed in 13 NHB women [28 (7) yr]. Local heating units (33°C) and laser-Doppler flowmetry (flux) probes were placed over each fiber. Increasing concentrations of acetylcholine were perfused alone (ACh; dissolved in lactated Ringer's) or with <i>N</i>^G-nitro-l-arginine methyl ester (ACh+l-NAME). Cutaneous vascular conductance was calculated (CVC = flux × mmHg^-1) and normalized to site-specific maximum (28 mM sodium nitroprusside + 43°C). Macrovascular endothelial function was assessed by brachial artery flow-mediated dilation (FMD) and handgrip-augmented FMD (FMD+HG). Salsalate treatment did not impact ACh-induced vasodilation overall (main effect, <i>P</i> = 0.24), but a treatment × site interaction effect emerged (<i>P</i> < 0.0001). ACh increased and ACh+l-NAME decreased after salsalate (both <i>P</i> ≤ 0.03), but this effect was small (Cohen's <i>f</i> = 0.19). Five-day salsalate treatment did not alter %FMD (<i>P</i> = 0.28) or %FMD+HG (<i>P</i> = 0.17). Cutaneous microvascular, but not macrovascular, function marginally improved after salsalate, indicating that inflammation via NF-κB pathways contributes to impaired cutaneous microvascular function in NHB women.<b>NEW & NOTEWORTHY</b> Our results show that cutaneous microvascular, but not macrovascular, function is improved after oral salsalate treatment in healthy non-Hispanic Black women. These data reveal that systemic inflammation via NF-κB pathways attenuates cutaneous microvascular function in this population.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1297-H1306"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966170","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":"Postpartum cardiac structure and organ homeostasis following regulatory T cell depletion in early pregnancy.","authors":"Evangeline A K Lovell, Amy L Wooldridge, Shanna L Hosking, Rianna J De Poi, Stacey J Savin, Lisa M Nicholas, Matthew Chapman, Sven Y Surikow, Laura J Parry, Stephane L Bourque, Sarah A Robertson, Alison S Care","doi":"10.1152/ajpheart.00374.2026","DOIUrl":"10.1152/ajpheart.00374.2026","url":null,"abstract":"<p><p>Maternal insufficiency in regulatory T (Treg) cells in pregnancy impairs maternal-fetal immune tolerance and uteroplacental vascular adaptation. Whether Treg cell insufficiency in pregnancy has maternal postpartum consequences is unknown. Using <i>Foxp3</i>^DTR mice, wherein diphtheria toxin (DT) is given to selectively deplete Foxp3⁺ Treg cells, we investigated whether early pregnancy Treg cell deficiency alters postpartum cardiometabolic outcomes. Transient Treg cell depletion was elicited by DT administration on <i>gestational days 3.5</i> and <i>5.5</i>, a protocol that causes defective decidual uterine spiral artery remodeling, uterine artery dysfunction, elevated fetal loss, and fetal growth restriction. Maternal Treg cell deficiency led to marked alterations in cardiac adaptations at 4-7 wk postpartum, including reduced left ventricular mass ([Formula: see text]29% end-diastolic and systolic left ventricular mass; both <i>P</i> ≤ 0.024), decreased aortic diameter ([Formula: see text]12%; <i>P</i> = 0.004), and increased fractional shortening ([Formula: see text]34%; <i>P</i> = 0.042). Constriction responses in the mesenteric arteries and aortae were unchanged. Metabolic parameters and blood pressure were unaffected; however, DT-treated dams exhibited persistent splenomegaly ([Formula: see text]40%; <i>P</i> = 0.001) and reduced kidney, uterine, and brain weights ([Formula: see text]7%-40%; all <i>P</i> ≤ 0.028). These findings demonstrate that Treg cell insufficiency in pregnancy alters maternal postpartum cardiac structure and organ homeostasis and supports investigation of Treg cell-targeted strategies to improve long-term maternal health.<b>NEW & NOTEWORTHY</b> In this study, we show that maternal Treg cell deficiency in early pregnancy leads to altered maternal cardiac structure and organ homeostasis in the early postpartum period. These findings imply that in addition to regulating pregnancy immune and vascular adaptation, Treg cells are also critical for maternal postpartum cardiovascular recovery.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1351-H1362"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928844","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":"Calcium handling in postinfarction arrhythmias: evidence from large animals.","authors":"Tristan Hellstrand, Godfrey L Smith, Mathis Korseberg Stokke","doi":"10.1152/ajpheart.00392.2026","DOIUrl":"10.1152/ajpheart.00392.2026","url":null,"abstract":"<p><p>Understanding the causes of ventricular arrhythmias after myocardial infarction (MI) remains a major challenge to academic and clinical medicine. Key concepts in the pathophysiology underlying such events are based on studies in rodents, in whom altered sarcoplasmic reticulum (SR) calcium handling is key even in chronic stages after MI. Since cardiac electrophysiology in rodents has important differences from humans, an overview of insights directly from large animals and humans is needed. Our objective was to provide a summary of existing literature on the role of SR calcium handling in ventricular tachyarrhythmias after the acute phase of MI in large animals and humans. We conducted a systematic search of original articles on calcium handling after MI in large animals and humans, summarized key findings, and assessed risk of bias in the included articles. Twenty-five studies explicitly measuring cellular calcium handling after MI in large animals or human tissue were included. Overall, the studies were somewhat ambiguous regarding calcium transient amplitude and kinetics, but consistently showed increased frequency of calcium sparks, calcium waves, delayed afterdepolarizations, and reduced t-tubule density, while some reported increased propensity for calcium alternans. Abundance and posttranslational modification of calcium handling proteins were less consistent. In conclusion, existing evidence from large animals and human material supports a role for altered calcium handling in ventricular arrhythmias after MI. However, the evidence is still limited. More studies in such models are needed to provide mechanistic explanations that can be used as a basis for development of new therapies.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1071-H1082"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787059","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":"ACE2 downregulation contributes to adverse cardiovascular and reproductive outcomes in female mice on high-fat diet.","authors":"Nour Abbes, Uma Priya Mohan, Parnia Mobasheran, Paula Dinh, Muntha Abbas, Eric Lazartigues, Xinping Yue","doi":"10.1152/ajpheart.00345.2026","DOIUrl":"10.1152/ajpheart.00345.2026","url":null,"abstract":"<p><p>Obesity is a growing concern among women of reproductive age, as it can significantly impact both maternal and fetal health. A potential mechanism linking obesity to cardiometabolic dysfunction is the imbalance between the classical (pressor) and the compensatory (protective) arms of the renin-angiotensin system (RAS). The objective of this study was to investigate how high-fat diet (HFD) impacts cardiovascular and reproductive health in female mice and its associated mechanisms, with an emphasis on the protective angiotensin-converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7) axis. Female C57BL/6J mice at 8 wk of age were assigned to either a HFD (60 kcal% fat) or a regular diet (RD, 22 kcal% fat). Following 10-12 wk of dietary exposure, HFD-fed females exhibited significantly greater weight gain and glucose intolerance compared with RD-fed controls. Telemetry recordings revealed that HFD exposure led to significantly elevated blood pressure (BP), increased heart rate, reduced spontaneous baroreflex sensitivity, and dampened parasympathetic tone. The aforementioned cardiometabolic dysfunction persisted or further exacerbated during pregnancy. Although HFD exposure did not alter fertility (ability to conceive), delivery, or litter size, offspring from HFD mothers suffered low birth weight and markedly increased postnatal mortality. Examination of the RAS revealed reduced ACE2 mRNA and protein expression in both the heart and the kidney of HFD-fed females. Importantly, Ang-(1-7) infusion in HFD-fed females starting 2 wk before mating improved glucose tolerance, reduced BP, and improved offspring survival. In conclusion, downregulation of ACE2/Ang-(1-7) axis contributes to HFD-induced cardiometabolic and reproductive dysfunction in female mice.<b>NEW & NOTEWORTHY</b> This study identifies downregulation of ACE2 in the setting of high-fat diet-induced obesity as a contributing factor to maternal cardiometabolic dysfunction and adverse pregnancy outcomes. Restoring ACE2/Ang-(1-7) function may have therapeutic value in improving cardiovascular and reproductive functions in females with obesity.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1229-H1241"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910703","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":"Beyond phenotypic classification: a roadmap to biology-driven precision heart failure care.","authors":"Cinzia Perrino, Roberta Paolillo, Martina Carotenuto, Pina Polese, Federica Ilardi, Giuseppe Giugliano, Giuseppe Gargiulo, Giovanni Esposito","doi":"10.1152/ajpheart.00625.2026","DOIUrl":"10.1152/ajpheart.00625.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1262-H1266"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904845","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}