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

{"title":"Changes in left ventricular diastolic flow dynamics in the neonatal transition period and beyond.","authors":"Kristian Sørensen, Solveig Fadnes, Tor Åge Myklebust, Lasse Løvstakken, Luc Mertens, Siri Ann Nyrnes","doi":"10.1152/ajpheart.00214.2025","DOIUrl":"10.1152/ajpheart.00214.2025","url":null,"abstract":"<p><p>Significant hemodynamic changes occur within the neonatal transition period including a sudden increase in pulmonary blood flow, disappearance of fetal shunts, and increase in systemic vascular resistance. How this affects left ventricular (LV) physiology and intraventricular flow dynamics is still poorly understood. Blood speckle tracking is a novel high frame rate echocardiographic technique that allows to visualize two-dimensional intraventricular flow dynamics. In this study, longitudinal changes in LV diastolic flow dynamics were explored in a prospective single-center design analyzing a total of 176 echocardiographic examinations in 36 healthy newborns from birth until 6 mo of age. Kinetic energy, energy loss, vorticity, and intraventricular pressure difference increased significantly from birth until 6-8 wk of age (<i>P</i> < 0.001 for all parameters). The increase in intraventricular pressure difference continued until 6 mo of age, whereas no further significant changes in the other quantitative LV flow parameters could be observed beyond 6-8 wk. Early after birth, diastolic vorticity was predominantly located at the anterior mitral valve leaflet whereas at 6 mo of age, vorticity was similar at the anterior compared with the posterior mitral valve leaflet. Overall, these results indicate that LV diastolic physiology and flow dynamics undergo substantial changes in early life. The observed changes in diastolic LV properties are likely associated with increased LV filling in the presence of increased pulmonary blood flow.<b>NEW & NOTEWORTHY</b> Assessment of left ventricular flow dynamics is highly feasible using high-frame rate echocardiography-based blood speckle tracking. In healthy newborns, left ventricular diastolic kinetic energy, energy loss, and vorticity significantly change during the first weeks, stabilizing after 6-8 wk, whereas intraventricular pressure difference continues to increase until 6 mo of age. These findings indicate that intraventricular flow dynamics can describe changes in cardiac physiology contributing to normal postnatal cardiovascular adaptation, maturation, and function.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1333-H1343"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973139","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":"Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes.","authors":"William B Horton, Kaitlin M Love, Justin M Gregory, Zhenqi Liu, Eugene J Barrett","doi":"10.1152/ajpheart.00826.2024","DOIUrl":"10.1152/ajpheart.00826.2024","url":null,"abstract":"<p><p>Vascular insulin resistance has emerged as a pivotal factor in the genesis of cardiovascular disease (CVD) in people with diabetes. It forms a complex pathogenic partnership with metabolic insulin resistance to significantly amplify the CVD risk of diabetes and other affected populations. Metabolic insulin resistance (characterized by quantitatively diminished insulin action on glucose metabolism in skeletal muscle, liver, and adipose tissue) is a hallmark of diabetes, obesity, and related conditions. In contrast, vascular insulin resistance is a less appreciated and not well-quantified complication of these conditions. Importantly, an impaired vascular response to insulin contributes directly to vascular dysfunction and over 40 years of research has convincingly shown that vascular and metabolic insulin resistance synergize to create an environment that predisposes individuals to CVD. In this review, we examine the multifaceted vascular actions of insulin, including its roles in regulating blood pressure, blood flow, endothelial health, and arterial stiffness. We also examine how these processes become disrupted in the setting of vascular insulin resistance, which subsequently undermines endothelial function, compromises tissue microvascular perfusion, and promotes vascular rigidity and atherosclerosis. We then highlight potential therapeutic strategies with demonstrated efficacy to improve vascular insulin sensitivity in people with diabetes and suggest that targeting disordered vascular insulin signaling holds promise not only for refining the functional understanding of vascular insulin resistance but also for developing innovative treatments with potential to reduce CVD risk and improve cardiovascular outcomes in people with diabetes.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"328 6","pages":"H1218-H1236"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973234","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":"Validation of magnetic resonance imaging-derived venous oxygen saturation and oxygen consumption measurements during exercise.","authors":"Rachel J Skow, Stephen J Foulkes, Hendrik Mugele, Dean R Perkins, Justin S Lawley, Corey R Tomczak, Michael D Nelson, Andre La Gerche, Mark J Haykowsky, Richard B Thompson","doi":"10.1152/ajpheart.00134.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00134.2025","url":null,"abstract":"<p><p>Accurate measurement of venous oxygen saturation ([Formula: see text]) is fundamental for quantifying oxygen consumption (V̇o₂) and its Fick determinants. This study evaluated the validity of a novel magnetic resonance imaging (MRI) approach using susceptometry-based oximetry (SBO) to noninvasively measure [Formula: see text] during exercise. First, [Formula: see text] was measured from an antecubital vein in 14 adults (26 ± 5 yr; 8 males) via portable blood analyzer (iSTAT) at rest and during two 5-min bouts of rhythmic handgrip exercise at 30% of maximum voluntary contraction, with temporally matched SBO measures of [Formula: see text] during an identical in-scanner exercise protocol. Separately, 21 adults (27 ± 6 yr; 8 males) completed incremental step ergometry exercise with simultaneous pulmonary V̇o₂ measurement (indirect calorimetry) and MRI-derived V̇o₂ from the Fick determinants (MRI_Fick), including inferior vena cava [Formula: see text] (SBO) and cardiac output (cardiac MRI). Agreement between methods was assessed by interclass correlation coefficients (ICCs), linear regression, and Bland-Altman plots. There was good to excellent agreement between iSTAT and SBO [Formula: see text] for arm exercise (ICC: 0.86, 95% CI: 0.71-0.93, <i>P</i> < 0.01; mean bias: +5.2%). Test-retest reliability demonstrated excellent agreement for [Formula: see text] measures between trials using iSTAT (ICC: 0.97; 95% CI: 0.93-0.96, <i>P</i> < 0.01; mean bias: -2.7%) and SBO (ICC: 0.90, 95% CI: 0.80-0.95, <i>P</i> < 0.01; mean bias: -0.3%), V̇o₂ calculated from MRI_Fick demonstrated excellent agreement with pulmonary V̇o₂ (ICC: 0.98, 95% CI: 0.97-0.99, <i>P</i> < 0.01; mean bias: +0.10 L/min). MRI-SBO-derived [Formula: see text] measurements demonstrated excellent reliability and strong agreement with both venous measures and respiratory gas analysis, validating this technique across a wide range of [Formula: see text] values during exercise.<b>NEW & NOTEWORTHY</b> Noninvasive MRI susceptometry-based [Formula: see text] measurements demonstrated excellent repeatability and validity against established direct blood sampling during localized handgrip exercise. The technique's accuracy for determining V̇o₂ during step ergometer exercise was validated through strong agreement between combined cardiac MRI and susceptometry-based Fick calculations and reference pulmonary measures, establishing this method as a reliable tool for noninvasive assessment of oxygen uptake and its Fick determinants across varying exercise intensities.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"328 6","pages":"H1179-H1192"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061946","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":"Biological sex influences relationships between cerebral pulsatility and white matter hyperintensities in aging adults.","authors":"M Erin Moir, Nicole A Loggie, Brandon G Fico, Sarean Harmoni A Gaynor-Metzinger, Alexander M Norby, Ryan D Zea, Anna J Howery, Leonardo A Rivera-Rivera, Laura B Eisenmenger, Oliver Wieben, Sterling C Johnson, Jill N Barnes","doi":"10.1152/ajpheart.00061.2025","DOIUrl":"10.1152/ajpheart.00061.2025","url":null,"abstract":"<p><p>Arterial stiffening with age, which is associated with elevated cerebral pulsatility in the intracranial arteries, is linked to structural alterations in the brain, including white matter hyperintensities (WMH). Biological sex differences exist in cerebral hemodynamics and Alzheimer's disease (AD) risk; yet, little is known regarding the impact of biological sex on the association between cerebral pulsatility and WMH. We studied 403 cognitively unimpaired middle-aged and older adults (45-91 yr, 272 females) who completed 3 T magnetic resonance imaging (MRI). Four-dimensional (4D) flow MRI provided measures of cerebral pulsatility index (PI) in multiple intracranial arteries. T2 fluid-attenuated inversion recovery images were analyzed for WMH volumes. In middle-aged adults, PI in the internal carotid arteries (ICA) and the right middle cerebral artery (MCA) was positively associated with WMH in females (all <i>P</i> < 0.01) but not in males (all <i>P</i> > 0.25). In older adults, PI in the left ICA and the MCAs was positively associated with WMH in males and females (all <i>P</i> ≤ 0.02). Also, in older adults, basilar artery PI was positively associated with WMH in females (<i>P</i> = 0.006) but not males (<i>P</i> = 0.31). These data suggest that, among cognitively unimpaired adults, elevated cerebral PI is linked to greater WMH; however, these relationships are influenced by sex and age such that female-specific relationships emerge in the anterior circulation in middle age, and in the posterior circulation in older adults. These findings may provide insights to vascular mechanisms contributing to sex differences in AD with advancing age.<b>NEW & NOTEWORTHY</b> The vascular mechanisms underlying the elevated prevalence of Alzheimer's disease among females remain unclear. In this study, we found that positive relationships between cerebral pulsatility in the anterior circulation and white matter hyperintensities (WMH) emerged in females in middle age but not until older adulthood in males. In addition, female-specific relationships were present between cerebral pulsatility in the posterior circulation and WMH in older adults.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1306-H1317"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958903","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":"Targeted circulating lipid mediators and immune cell gene transcripts after ST-elevation myocardial infarction.","authors":"Dae Hyun Lee, Gunjan Upadhyay, Siddabasave Gowda B Gowda, Vasundhara Kain, Md Abdul Malek, Nicholas Carris, Samip Vasaiwala, Timothy J Yeatman, Guilherme H Oliveira, Shu-Ping Hui, Ganesh V Halade","doi":"10.1152/ajpheart.00494.2024","DOIUrl":"10.1152/ajpheart.00494.2024","url":null,"abstract":"<p><p>Residual inflammation drives atherogenesis to atherosclerosis and myocardial infarction, which triggers acute inflammation. In preclinical studies, polyunsaturated fatty acids-derived specialized pro-resolving mediators (SPMs) have been shown to promote recovery after myocardial infarction (MI), in contrast to proinflammatory lipid mediators (PIMs). However, the dynamic changes of lipid mediators after ST-elevation myocardial infarction (STEMI), particularly after percutaneous coronary intervention (PCI) and respective gene transcripts, are poorly understood. Therefore, the study aimed to assess the early dynamic changes in circulating lipid mediators and lipid pathway transcripts in patients with STEMI who undergo PCI. In this prospective observational clinical study, patients with STEMI (<i>n</i> = 10) and control subjects (<i>n</i> = 6) were included. Plasma samples for lipid mediator profiling (targeted oxylipids) and whole blood for inflammation-related transcript expression were collected at baseline before PCI, 2-, and 24-h post-PCI. A total of 10 patients with STEMI received PCI with a mean age of 53.3 yr, 90% male. Linoleic acid and docosapentaenoic acid levels were higher in patients with STEMI. A subset of PIM levels [hydroxyeicosatetraenoic acids, prostaglandin (PG)E₂] was elevated at the baseline, with a subsequent decrease in circulating levels at 2 h after PCI [thromboxanes, leukotriene B4 (LTB₄), 20-hydroxy-LTB₄]. A subset of SPM levels was elevated at the baseline of STEMI suggestive overlap of inflammation-resolution signaling. The temporal kinetics of lipid mediators showed that both the initiation of inflammation and the resolution process start simultaneously and continue as an endogenous repair mechanism during STEMI. Therefore, approaches to increase these endogenous bioactive resolution mediators content and/or efficacy before PCI should be considered in treating patients with MI.<b>NEW & NOTEWORTHY</b> Polyunsaturated fatty acids-derived SPMs are decisive in myocardial infarction (MI) recovery, contrasting with proinflammatory lipid mediators (PIMs). A study on early lipid changes post-percutaneous coronary intervention (PCI) in patients with STEMI shows baseline elevation and post-PCI decrease in PIMs, whereas some SPM levels remain elevated. Findings highlight simultaneous inflammation and resolution in STEMI, emphasizing the need to enhance endogenous repair processes before PCI for better MI treatment.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1351-H1360"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869289","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":"Functional capacity and skeletal muscle morphology are linked to N-terminal proBNP but not left ventricular ejection fraction in patients with heart failure.","authors":"Jakob Wang, Thomas Groennebaek, Roni Nielsen, Kasper Pryds, Frank Vincenzo de Paoli, Hans Erik Bøtker, Kristian Vissing","doi":"10.1152/ajpheart.00275.2025","DOIUrl":"10.1152/ajpheart.00275.2025","url":null,"abstract":"<p><p>Chronic heart failure (CHF) involves skeletal muscle abnormalities, including atrophy, inflammation, mitochondrial dysfunction, and fibrosis, which impair contractile function. This study examines whether muscle deterioration correlates with CHF disease severity by assessing the relationship between circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, left ventricular ejection fraction (LVEF), and muscle characteristics in patients with CHF. In 36 patients with CHF (LVEF ≤ 45%, New York Heart Association class I-III), we measured circulating NT-proBNP concentrations, LVEF, muscle strength and functional measures, and myocellular features, including fiber type-specific cross-sectional area (CSA), muscle stem cell (MuSC) and myonuclei content, and capillary density. Also, muscle mitochondrial function was evaluated. The concentration of NT-proBNP inversely correlated with muscle strength (<i>R</i>² = 0.25, <i>P</i> < 0.01), mean fiber CSA (<i>R</i>² = 0.15, <i>P</i> = 0.04), and MuSC content (<i>R</i>² = 0.37, <i>P</i> < 0.01). Moreover, a nonsignificant inverse correlation was observed for capillary density (<i>R</i>² = 0.12, <i>P</i> = 0.06). The strength of associations between NT-proBNP, fiber CSA, and capillary density was primarily driven by fiber type-specific correlations. Associations with MuSC content were equally strong across fiber types. No correlation was observed for measures of mitochondrial function. For LVEF, a nonsignificant correlation was observed only for overall MuSC content (<i>R</i>² = 0.11, <i>P</i> = 0.07). Skeletal muscle deterioration in patients with CHF correlates with NT-proBNP, but not LVEF, suggesting that NT-proBNP concentration constitutes a stronger indicator of the link between CHF severity and skeletal muscle decline than LVEF as function parameter. Our findings highlight circulating NT-proBNP concentrations as a potential biomarker for the identification of patients at risk of experiencing skeletal muscle deterioration.<b>NEW & NOTEWORTHY</b> In this study, the authors reveal that elevated NT-proBNP levels are inversely associated with muscle function and cellular features in patients with chronic heart failure (CHF), including muscle fiber cross-sectional area, muscle stem cell content, and capillarization. NT-proBNP appears to be a more reliable marker than left ventricular ejection fraction (LVEF) for identifying skeletal muscle abnormalities and predicting muscle loss in CHF, offering potential for early intervention and personalized care.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1344-H1350"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960049","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":"Corrigendum for Bigler et al., volume 327, 2024, p. H1124-H1131.","authors":"","doi":"10.1152/ajpheart.00481.2024_COR","DOIUrl":"https://doi.org/10.1152/ajpheart.00481.2024_COR","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"328 5","pages":"H1086"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957546","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}