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

{"title":"Long-term genetic Orai1 inhibition modulates excitation-contraction coupling in female adult mouse ventricular cardiomyocytes.","authors":"Fiona Bartoli, Pauline Le Gourriérec, Baptiste Rode, Fabrice Antigny, Romain Perrier, David J Beech, Ana Maria Gomez, Jean-Pierre Benitah, Jessica Sabourin","doi":"10.1152/ajpheart.00101.2026","DOIUrl":"10.1152/ajpheart.00101.2026","url":null,"abstract":"<p><p>The physiological role of the Orai1 channel, a store-operated Ca²⁺ channel in adult ventricular cardiomyocytes, remains incompletely defined. Here, we report that Orai1 may contribute to excitation-contraction coupling (ECC) in a sex-specific manner. Using a mouse model with cardiac-specific expression of a dominant-negative human Orai1^R91W mutant (C-dnO1), we found elevated Ca²⁺ transients and Ca²⁺ spark amplitudes in female C-dnO1 mice in comparison with littermate wild-type (WT) controls, but not in male mice. The Orai1 protein expression, cellular distribution, and store-operated Ca²⁺ entry activity were similar in WT males and females and equally diminished in both sexes with C-dnO1 expression. These findings reveal that chronic functional suppression of Orai1 abrogates sex differences in cardiomyocyte ECC, uncovering a novel mechanistic contribution of Orai1 to sexual dimorphism in cardiac function.<b>NEW & NOTEWORTHY</b> This short report reveals a novel mechanistic contribution of the Ca²⁺ channel Orai1 to sexual dimorphism in cardiac physiology. We demonstrated that the chronic functional suppression of Orai1 abrogates sex differences in cardiomyocyte excitation-contraction coupling.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1702-H1710"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607731","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 neutrophil-renal-cholesterol axis: a new link between infection and atherosclerosis.","authors":"Dipankar Ash, Masuko Ushio-Fukai, Tohru Fukai","doi":"10.1152/ajpheart.00257.2026","DOIUrl":"10.1152/ajpheart.00257.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1541-H1544"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626447","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":"Reply to Sbarra et al.","authors":"Hannah Takahashi Oakland, Paul Heerdt, Kendall Hunter, Inderjit Singh","doi":"10.1152/ajpheart.00243.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.00243.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"330 5","pages":"H1711-H1712"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809642","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":"Diet modulates cardiac metabolic stress during anthracycline treatment.","authors":"Kyoungmin Kim, Yaqi Gao, Tanvi Shankar, Anja Karlstaedt","doi":"10.1152/ajpheart.00745.2025","DOIUrl":"10.1152/ajpheart.00745.2025","url":null,"abstract":"<p><p>Diet is a modifiable determinant of cardiovascular risk and may influence tolerance to cancer therapies. The mechanisms by which specific dietary components affect cardiac metabolism during anthracycline treatment remain poorly defined, limiting the incorporation of dietary recommendations into treatment guidelines. Here, we integrated heart proteomics data from patients treated with or without anthracyclines with a genome-scale reconstruction of human cardiac metabolism (CardioNet). Using constraint-based flux analysis, we conducted >30,000 in silico simulations of diet scenarios generated from chemical profiles of ∼500 foods curated in the Periodic Table of Food Initiative. These simulations revealed that diets enriched in rapidly absorbable sugars and depleted of essential fatty acids impair cardiac metabolic efficiency, increasing reactive oxygen species production and the demand for purine salvage fluxes. These predicted metabolic patterns were consistent with plasma metabolomics from patients treated with anthracyclines, validating our findings. Computational modeling of 39 recipes across six cuisines revealed cardiometabolic effects of omnivorous versus vegan diets in patients. Modeling of a healthy vegan diet increased cardiometabolic efficiency compared with a healthy omnivorous diet in patients treated with anthracyclines, independent of the culinary background. Our approach demonstrates that integrating the molecular composition of food with genome-scale metabolic models enables systematic analysis of diet patterns for translational testing. Ultimately, these in silico studies provide a framework for trials and may inform dietary recommendations for improving cardiometabolic health.<b>NEW & NOTEWORTHY</b> We developed a systems biology framework to predict how diet influences cardiac metabolism during cancer therapy. Across >30,000 in silico diet simulations, we identified nutrient patterns that either exacerbate or mitigate anthracycline-induced metabolic stress. These findings demonstrate how computational modeling can uncover diet-metabolism interactions driving cardiotoxicity and guide dietary interventions.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1454-H1465"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429797","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":"Adropin and blood pressure variability: new directions for hypertension prevention.","authors":"Abigail E Cullen, Young Deanna Choi, Skylyn Ferguson, Aida Sabouri","doi":"10.1152/ajpheart.00987.2025","DOIUrl":"10.1152/ajpheart.00987.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1359-H1360"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497325","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":"Do small-conductance Ca²⁺-activated K⁺-channels contribute to ventricular repolarization in human heart failure?","authors":"Aiman Saleh A Mohammed, Vivien Demeter-Haludka, Alaa Amin E Abdelmagid, Leila Topal, Naveed Muhammad, Gábor Mohácsi, Benjamin Paskuj, Gergő Bitay, Zsófia Kohajda, Kálmán Benke, Alex Ali Sayour, Tamás Radovits, Miklós Bitay, László Virág, Norbert Jost, István Baczkó, András Varró, Béla Merkely, Norbert Nagy","doi":"10.1152/ajpheart.00540.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00540.2025","url":null,"abstract":"<p><p>Chronic heart failure constitutes a clinical syndrome characterized by substantial attenuation of repolarization reserve resulting from electrical remodeling. The small-conductance Ca²⁺-activated K⁺ channel (SK) has been reported to undergo upregulation in animal heart failure models and in human preparations, however its exact function is not fully understood. This study aims to elucidate the functional role of SK channels in end-stage human heart failure. SK-protein expression of undiseased and failed human ventricular tissue was investigated by Western-blot technique. Action potentials were measured by standard microelectrode technique from right ventricular papillary muscles of undiseased hearts and from right and left papillary muscles and from left midmyocardial tissue slices of failing hearts. Ionic currents were recorded by the whole-cell configuration of the patch-clamp technique on isolated cells obtained from left ventricles of failing hearts. Failing hearts exerted consistent action potential lengthening and lacked spike-and-dome compared to undiseased hearts. Western-blot revealed identical SK-expression between undiseased and failing hearts. 100 nM apamin, a commonly used selective SK-channel inhibitor, failed to alter action potential duration values of the failing hearts in left and right endocardial preparations and in left midmyocardium. Furthermore, no apamin sensitive current was identified in isolated cells. It was found weak coupling between SK2-channels and L-type Ca²⁺ channels. These results do not confirm the results of previous studies claiming an important role of SK-channels in the repolarization of human failing heart.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809666","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":"Correction for Baba et al., volume 314, 2018, p. H659-H668.","authors":"","doi":"10.1152/ajpheart.00452.2017_COR","DOIUrl":"https://doi.org/10.1152/ajpheart.00452.2017_COR","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"330 5","pages":"H1540"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759970","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":"Influence of spontaneous bursts of muscle sympathetic nerve activity on superficial femoral artery and femoral vein flow at rest and during slow deep breathing.","authors":"Massimo Nardone, Kate N Thomas, Jui-Lin Fan, Greer E Pugh, James P Fisher","doi":"10.1152/ajpheart.00765.2025","DOIUrl":"10.1152/ajpheart.00765.2025","url":null,"abstract":"<p><p>The effect of slow deep breathing (SDB) on the dynamic transduction of sympathetic nerve activity to the superficial femoral artery (SFA), femoral vein (FV), and blood pressure was determined. In 12 healthy volunteers (five women, 25 ± 7 yr, means ± SD), simultaneous imaging of the SFA and FV, along with contemporary measures of muscle sympathetic nerve activity (MSNA), was obtained and signal-averaging techniques were used to quantify sympathetic neurovascular transduction at rest (baseline) and during 5 min SDB at 6 breaths/min. At baseline, MSNA bursts were followed by transient increases in mean arterial pressure (MAP; peak +3.0 ± 1.2 mmHg), decreases in SFA flow (nadir -6.3 ± 4.5 mL/min), and small, inconsistent increases in FV flow (peak +4.3 ± 6.7 mL/min). SDB decreased MSNA burst frequency and burst incidence by ∼30%, whereas MAP was unchanged. During SDB, MSNA bursts were followed by greater increases in MAP (peak +6.0 ± 2.4 mmHg, <i>P</i> < 0.001 vs. baseline), greater decreases in SFA flow (nadir -9.8 ± 4.0 mL/min, <i>P</i> = 0.002 vs. baseline), and a tendency for a greater increase in FV flow (peak +20.6 ± 21.0 mL/min, <i>P</i> = 0.051). Therefore, although SDB reduces MSNA, the augmented MSNA transduction to blood pressure may help to preserve MAP. SDB evoked greater reductions in SFA flow and increases in FV flow following an MSNA burst, which may work synergistically with the respiratory muscle pump to facilitate venous return. Collectively, these findings highlight the important role played by MSNA in the dynamic regulation of peripheral blood flow, venous return, and blood pressure.<b>NEW & NOTEWORTHY</b> Sympathetic neurovascular transduction to mean arterial pressure (MAP), superficial femoral artery (SFA), and femoral vein (FV) flow were quantified at baseline and during slow deep breathing (SDB). MAP was unchanged during SDB, whereas MSNA was decreased, and sympathetic transduction to MAP, SFA flow, and FV flow (tendency) were increased. Respiratory-coupled oscillations in MSNA, SFA flow, and FV flow appear to work synergistically with the respiratory muscle pump to facilitate venous return during SDB.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1433-H1445"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508789","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":"Plasma metabolites, blood-borne microvesicles, and history of preeclampsia as predictors of coronary artery calcification in postmenopausal women.","authors":"Vladimir Dokic, Muthuvel Jayachandran, Lisa Vaughan, Sonja Suvakov, Jennet Hatamova, Paul Gavrilovici, Song Zhang, Oscar Garcia Valencia, Vesna D Garovic","doi":"10.1152/ajpheart.00057.2026","DOIUrl":"10.1152/ajpheart.00057.2026","url":null,"abstract":"<p><p>Compared with men, women with similar coronary artery calcification (CAC) scores face higher cardiovascular disease (CVD) mortality. We posited that circulatory factors, such as blood-borne extracellular vesicles (EVs) and metabolites, may be associated with the development of CAC and subsequent CVD in postmenopausal women. In addition, we hypothesized that a history of preeclampsia (PE), a sex-specific risk factor, might be a contributing factor. Clinical data were obtained from medical records for postmenopausal women (median age 60 yr) free of cardiovascular events with (<i>n</i> = 29) and without (<i>n</i> = 29) CAC. EVs per microliter plasma were quantified by digital flow cytometry, and plasma metabolites were measured using gas chromatography-mass spectrometry. CACs were measured by computer tomography and reported as the Agatston score. Patients with, versus those without, CAC demonstrated <i>1</i>) less favorable cardiovascular and metabolic profiles; <i>2</i>) elevation in six EV populations, including those positive for tissue factor, CD3 (T-cells), SM22α (smooth muscle cells), Pref-1 (adipocytes), fatty acid-binding protein 4 (adipocytes/macrophages), and p16 (senescent cells); <i>3</i>) significantly higher levels of proline, allothreonine (amino acid metabolism), and ribitol (carbohydrate metabolism), and lower levels of lactic acid (carbohydrate metabolism); and <i>4</i>) significantly increased risk of developing CVD and chronic kidney disease (CKD) (<i>P</i> < 0.05 for all). In the CAC-positive group, women with PE versus those with normotensive pregnancy histories demonstrated a four times higher risk of developing cardiovascular events or CKD later in life (<i>P</i> = 0.028). Selected plasma metabolites, EVs, and PE history could serve as biomarkers and potential therapeutic targets for CAC and CVD in postmenopausal women.<b>NEW & NOTEWORTHY</b> Circulating extracellular vesicles, proinflammatory/pro-oxidant metabolites, and history of preeclampsia may be used as biomarkers for diagnosis of early CAC in postmenopausal women.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1578-H1589"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669800","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":"Aortic 4D flow CMR for the assessment of hemodynamics in aortic stenosis: association with markers of cardiac decompensation and remodeling.","authors":"Alexander Gotschy, Christian Binter, Rabea Schlenker, Felix C Tanner, Robert Manka, Sebastian Kozerke","doi":"10.1152/ajpheart.00043.2026","DOIUrl":"10.1152/ajpheart.00043.2026","url":null,"abstract":"<p><p>Aortic stenosis (AS) induces complex alterations in ascending aortic flow, including increased turbulent kinetic energy (TKE), altered velocity profiles, and changes in flow organization, which can be quantified using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR). The physiological relevance of these flow-derived parameters with respect to left ventricular (LV) adaptation remains incompletely understood. We investigated the associations between 4D flow CMR-derived hemodynamic metrics and established markers of LV decompensation and remodeling in patients with AS. Fifty-nine patients with AS (70 ± 14 yr) underwent 4D flow CMR using a Bayesian multipoint phase-contrast sequence with k-t PCA acceleration and three velocity-encoding steps in each direction. Quantified parameters included peak TKE, stroke volume-normalized systolic TKE (normalized TKE_sys), peak velocity, jet angle, relative flow displacement, and mean helicity. Associations with NT-proBNP and indexed LV mass were analyzed. Peak TKE, normalized TKE_sys, and peak systolic velocity were significantly associated with both indexed LV mass and NT-proBNP, whereas mean helicity was associated with indexed LV mass only. In contrast, jet angle and flow displacement showed no relationship with either marker of LV decompensation and remodeling. During long-term follow-up, no 4D flow CMR parameter was associated with adverse clinical events, likely due to timely valve replacement in most patients. In conclusion, these findings indicate that flow energetics-particularly TKE and peak systolic velocity-most closely capture the hemodynamic burden imposed on the LV supporting their physiological relevance in AS. Isolated descriptors of flow geometry, in contrast, have not shown to reflect maladaptive LV remodeling.<b>NEW & NOTEWORTHY</b> This study used advanced four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) to investigate alterations in aortic flow of patients with aortic stenosis and its relation to left ventricular remodeling and decompensation. It shows that turbulent kinetic energy, which is a measure of irreversible energy loss downstream of a stenotic valve, and peak flow velocity are the characteristics, which best capture the hemodynamic burden imposed on the left ventricle (LV). In contrast, geometric flow descriptors such as jet angle and flow displacement lacked physiological relevance.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1446-H1453"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455266","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}