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

{"title":"Mouse Offspring Exposed to Preeclampsia/Eclampsia-like Symptoms Exhibit Cerebral Hypoperfusion & Mild Cognitive Impairment at 2 months of age.","authors":"Karen Saffold, Andrea Tall, A'Kaychia T Lowery, Tyranny Pryor, Maria Jones-Muhammad, Qingmei Shao, Junie P Warrington","doi":"10.1152/ajpheart.00711.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00711.2025","url":null,"abstract":"<p><p>Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of organ damage, after the 20^th week of pregnancy. Children born to mothers with preeclampsia or eclampsia (new-onset seizures during pregnancy) are more likely to develop learning and memory deficits and are more susceptible to neurovascular diseases compared to those born from normal pregnancies. The contributing mechanisms are unknown. In this study, we assessed whether exposure to reduced uteroplacental perfusion (RUPP), modeling placental hypoperfusion and preeclampsia, with or without pentylenetetrazol (PTZ) injection (to induce seizures and model eclampsia), results in cognitive impairment, Alzheimer's disease markers, and regional cerebral perfusion changes in adult offspring. On gestational day (GD)13.5, pregnant C57BL/6 mice (n=22) underwent Sham or RUPP surgery followed by injection or no treatment with PTZ (40 mg/kg) on GD18.5. At 2 months of age, spatial learning and cerebral perfusion were measured in randomly selected offspring or averaged to obtain mean data per sex, per litter (n=4-6 data points per group/treatment). RUPP-exposed offspring took a longer distance and made more errors navigating the Barnes maze. Cerebral perfusion was reduced in offspring exposed to RUPP, specifically in the prefrontal cortex, superior sagittal sinus, and whole brain. There was a significant reduction in perfusion in seizure-exposed offspring in the superior sagittal and transverse sinuses, whole brain, and cerebellum. Our results support the hypothesis that exposure to preeclampsia/eclampsia-like symptoms leads to mild learning impairment through reduced cerebral perfusion to cortical regions and decreased drainage of waste from the brain via the cerebral sinuses.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832620","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":"Sex-dependent myocardial necrosis-like signaling in rats with heart failure due to chronic pressure overload.","authors":"Csaba Horváth, Izabela Jarabicová, Jaroslav Hrdlička, Andrea Marciníková, Jan Neckář, Eva Nekvindová, Veronika Olejníčková, Adriana Adameová","doi":"10.1152/ajpheart.00064.2026","DOIUrl":"10.1152/ajpheart.00064.2026","url":null,"abstract":"<p><p>Sex profoundly influences cardiac adaptation to stressful stimuli; however, sex-specific mechanisms underlying heart failure (HF) due to necrosis-like cell death remain unclear. Using a neonatal rat model of abdominal aortic constriction, which mimics pressure overload-induced HF, we investigated cardiac function and morphology and provided a comprehensive molecular analysis of cell death pathways. Although necroptosis was evident in failing hearts of both sexes, albeit with more excessive remodeling in males, pyroptosis and ferroptosis were not prominent. At the cellular level, macrophages likely underlie this damage via different mechanisms in each sex. In females, the upstream activators of necroptosis indicated a proinflammatory environment, with a role of tumor necrosis factor-mediated canonical pathway involving receptor-interacting protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain-like pseudokinase. Conversely, in males, RIP3 activation was linked to an altered redox status and increased mitochondrial DNA oxidation. These sex-divergent pronecroptotic events underscore the necessity for personalized therapeutic strategies targeting distinct cell-damaging molecular pathways to improve HF outcomes.<b>NEW & NOTEWORTHY</b> This study identifies necroptosis as a key pathomechanism in pressure overload-induced heart failure, with sex-dependent, prodeath molecular events. Novel findings indicate distinct pronecroptotic triggers: in males, necroptosis is driven by oxidative stress and mitochondrial DNA damage, whereas in females, a proinflammatory pathway involving tumor necrosis factor and compensatory mitochondrial biogenesis predominates. Pyroptosis and ferroptosis do not appear to be prominent. These sex-specific molecular necrosis-like divergences are important for developing personalized therapeutic strategies for heart failure.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1673-H1688"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697231","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":"Publisher's note.","authors":"","doi":"10.1152/ajpheart.00261.2026_NOT","DOIUrl":"https://doi.org/10.1152/ajpheart.00261.2026_NOT","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"330 5","pages":"H1713"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809617","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":"Altered endothelial function in high-performance military fighter pilots.","authors":"Antonio Nesci, Alessandro Scagliusi, Vittorio Ruggieri, Francesca Romana Ponziani, Eugenio Agostino Parati, Pierandrea Trivelloni, Marco Lucertini, Luca Santoro, Angela Di Giorgio, Alessia D'Alessandro, Claudia Carnuccio, Pietro Perelli, Angelo Santoliquido","doi":"10.1152/ajpheart.00541.2025","DOIUrl":"10.1152/ajpheart.00541.2025","url":null,"abstract":"<p><p>High-performance fighter pilots are routinely subjected to extreme mechanical and physiological stressors, including exposure to high +Gz accelerations that may impact vascular health. In this short report, we evaluated endothelial function in 20 Eurofighter Typhoon (F-2000A) pilots and 19 matched control pilots flying nonhigh-G aircraft (KC-767A). Flow-mediated dilation (FMD) of the brachial artery was measured before and after flight sorties to assess vascular response. FMD values were lower after flight compared with preflight measurements, reflecting a significant main effect of time across the entire cohort (<i>P</i> < 0.05). Within-group analyses revealed a larger absolute reduction in FMD in F-2000A pilots (median = 10.02%-6.45%) compared with controls (9.40%-8.80%). However, the absence of a significant time × group interaction indicates that this response was not statistically different between pilot groups. In addition, F-2000A pilots exhibited smaller arterial diameters at rest and a significant postflight increase in baseline vessel caliber (3.81-4.13 mm; <i>P</i> < 0.001), suggesting a transient vasodilatory response potentially related to thermal or hemodynamic stress. These findings suggest an acute endothelial response to the high-performance flight environment. This study underscores the need for continued cardiovascular surveillance in high-performance aviators and supports further investigation of FMD as a noninvasive marker of vascular function within structured aeromedical follow-up programs.<b>NEW & NOTEWORTHY</b> This study is the first to evaluate endothelial function in fighter pilots exposed to high Gz (up to +9). Results indicate a postflight reduction in flow-mediated dilation (FMD) and time-dependent vascular changes associated with high-performance flight exposure. These findings highlight the potential value of FMD as a noninvasive tool for monitoring cardiovascular health and developing targeted aeromedical follow-up strategies for high-performance aircrew.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1368-H1374"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484358","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":"Combined high-fat, high-sucrose diet and streptozotocin treatment induces cardiometabolic heart failure with preserved ejection fraction in mice.","authors":"Andre Heinen, Andre Spychala, Lucas Ballmann, Stefanie Gödecke, Zewa Faradj, Florian Bresch, Martina Krüger, Katharina Bottermann, Heba Zabri, Jens Fischer, Patrick Petzsch, Axel Gödecke","doi":"10.1152/ajpheart.00843.2025","DOIUrl":"10.1152/ajpheart.00843.2025","url":null,"abstract":"<p><p>Diabetes is associated with an increased incidence of heart failure with preserved ejection fraction (HFpEF), but the underlying mechanisms are poorly understood. A shortage of mouse models reflecting the diverse HFpEF pathophysiology contributes to this inadequate understanding of disease mechanisms. We conducted a comprehensive analysis of a nongenetic, inducible type 2 diabetes mellitus (T2DM) mouse model about its suitability as a preclinical model of cardiometabolic, diabetes-induced HFpEF. T2DM was induced in C57Bl/6 mice by a high-fat/high-sucrose diet and a low-dose streptozotocin (DIO-STZ). Cardiac function was assessed in vivo by echocardiography and left ventricular catheterization and in vitro using the isolated perfused heart. Structural, molecular, and bioenergetic disturbances were analyzed by immunohistochemistry, RNA-seq, qPCR, Western blot, and extracellular flux analysis of myocardial tissue. Blood glucose, fatty acids, and ketone body levels were elevated, and insulin levels were reduced in DIO-STZ compared with chow. DIO-STZ mice showed an HFpEF phenotype with reduced cardiac output, end-diastolic volume, and increased filling pressure. No differences in myocardial fibrosis or in vitro stiffness were detected between DIO-STZ and chow. RNA-Seq pointed toward disturbances in lipid and ketone metabolism. Extracellular flux analysis revealed increased fatty acid oxidation capacity without differences in glucose metabolism. No general mitochondrial dysfunction was observed, but a reduced capacity for β-hydroxybutyrate oxidation. The diabetic DIO-STZ mouse model showed a pronounced functional HFpEF phenotype with underlying mechanisms that remarkably differ from other HFpEF models, making the DIO-STZ model a relevant extension of the range of HFpEF mouse models, especially for investigating molecular mechanisms or therapeutic interventions in diabetes-associated HFpEF.<b>NEW & NOTEWORTHY</b> Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome whose pathophysiological mechanisms are incompletely understood, potentially due to a lack of preclinical models reflecting the broad range of pathophysiological aspects. We describe a diabetic DIO-STZ mouse model showing a pronounced HFpEF with underlying mechanisms that remarkably differ from other HFpEF models, making this model a relevant extension of the range of HFpEF models, especially for investigating molecular mechanisms or therapeutical interventions in diabetes.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1375-H1390"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479542","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":"Neural mechanisms underlying blood pressure dynamics and cardiovascular control.","authors":"Zoran Matić, Vincenzo Catrambone, Gaetano Valenza","doi":"10.1152/ajpheart.00803.2025","DOIUrl":"10.1152/ajpheart.00803.2025","url":null,"abstract":"<p><p>Blood pressure regulation involves bidirectional brain-heart interactions mediated by both neurochemical signals and mechanosensitive pathways that include recently identified piezo receptors. We review current findings on the dynamic interplay between neural activity and blood pressure, highlighting insights from neuroimaging, systemic electrophysiology, and cellular biology. At a systemic level, blood pressure dynamics is regulated by coordinated oscillatory patterns across brain, cardiac, and respiratory signaling that couple with autonomic outflow and vascular pulsatility. Central autonomic networks, sympathetic-parasympathetic activity, and beat-to-beat blood pressure variability are mainly involved in such bidirectional interactions. At the cellular level, astrocytes, pericytes, endothelial cells, and cardiac and neural glia integrate mechanical pressure signals with metabolic and synaptic activity, forming distributed mechanosensory networks within the neurovascular unit and the cardiac autonomic nervous system. We show that optimal perfusion depends on arterial pressure remaining above a critical threshold to maintain vascular patency, with autoregulatory, metabolic, neurogenic, and glia-mediated mechanisms buffering systemic pressure fluctuations. When perfusion falls, astrocyte- and pericyte-dependent baroreflex mechanisms increase sympathetic drive, whereas pressure surges and altered arterial compliance promote vasoconstriction through coordinated neurovascular and central-autonomic responses. Pathological changes in arterial compliance and pulsatility, including loss of Windkessel function and nonphysiological flow states, distort neural pressure sensing and contribute to cardiovascular, cerebrovascular, and cognitive dysfunction and altered emotional processing. Invasive and noninvasive neuromodulation strategies may offer therapeutic potential by restoring physiological mechanosensory and autonomic control. These insights highlight the importance of mapping systemic central-autonomic networks and cell-specific neuromechanotransduction in health and in neurological, cardiovascular, and psychiatric disorders (1).</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1553-H1577"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637902","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":"Quantifying endothelial glycocalyx deformation by fluid shear stress.","authors":"Zhuoxin Li, Xiangyu Zheng","doi":"10.1152/ajpheart.00217.2026","DOIUrl":"10.1152/ajpheart.00217.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1391-H1393"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519641","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":"Could exercise intercept the profibrotic and stiffening trajectory of HFpEF progression in a clinically faithful porcine LV pressure-overload model?","authors":"Siluleko A Mkhize, Ashmeetha Manilall, Frederic S Michel","doi":"10.1152/ajpheart.00230.2026","DOIUrl":"10.1152/ajpheart.00230.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1420-H1422"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580197","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":"Mast cells in failing human hearts demonstrate transcriptomic activation of pathways involved in cardiac remodeling.","authors":"Mikael Sandstedt, Markus Johansson, Marianne Jonsson, Kristina Vukusic, Benjamin Ulfenborg, Maria Sandstedt, Lillemor Mattsson Hultén, Victoria Rotter Sopasakis, Göran Dellgren, Anders Jeppsson, Jane Synnergren, Joakim Sandstedt","doi":"10.1152/ajpheart.00921.2025","DOIUrl":"10.1152/ajpheart.00921.2025","url":null,"abstract":"<p><p>Intracardiac mast cells (CMCs) have previously been shown to contribute to adverse remodeling and heart failure in animal models. As CMCs in human hearts remain unexplored, the aim of this study was to investigate the pathophysiological relevance of human CMCs through transcriptomic profiling. Biopsies were collected from the four heart chambers of heart failure patients undergoing heart transplantation surgery (<i>n</i> = 9), as well as from deceased organ donors without chronic heart failure (<i>n</i> = 5). Using flow cytometry, C-kit⁺CD45⁺ CMCs and C-kit^-CD45⁺ hematopoietic cells were identified in all failing and nonfailing hearts and were sorted for RNA sequencing analysis. In comparison with other hematopoietic C-kit^-CD45⁺ cells and CMCs in nonfailing hearts, CMCs in failing hearts demonstrated significant activation of pathways involved in cardiac remodeling and heart failure, including fibrosis-associated and inflammatory pathways. Our results support a role for mast cells in human heart failure and constitute the first in-depth characterization of mast cells in the nonfailing and failing human heart.<b>NEW & NOTEWORTHY</b> Intracardiac mast cells (CMCs) have been shown to contribute to remodeling and fibrosis in animal models. No phenotypical characterization of human CMCs has been conducted before the current transcriptomic profiling study. CMCs isolated from failing human hearts demonstrated activated pathways involved in cardiac remodeling and fibrosis, both compared with other hematopoietic cells and to CMCs in nonfailing hearts. The study suggests that CMCs may constitute a novel candidate for modulation in human heart failure.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1491-H1507"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455203","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":"A race against time: timing constraints of cardiac filling and athletic performance.","authors":"Luke W Spencer, M Darragh Flannery, Kristel Janssens, Youri Bekhuis, Leah Wright, Erin J Howden, Tim Van Puyvelde, David L Prior, Amy M Mitchell, Stephanie J Rowe, Stephen J Foulkes, Andre La Gerche","doi":"10.1152/ajpheart.00896.2025","DOIUrl":"10.1152/ajpheart.00896.2025","url":null,"abstract":"<p><p>Cardiac filling is constrained by a reduced ejection time and diastolic period as heart rate increases during exercise. We compared cardiac filling dynamics in endurance athletes and controls during exercise to determine how athletic status influences hemodynamic constraints during exercise. Thirty-two participants (21 endurance athletes and 11 controls) underwent exercise echocardiography at 20, 40, and 60% of peak power output. We measured cardiac timing, stroke volume (SV), and flow rates (SV indexed to body surface area and phase duration). Data were analyzed using linear mixed models. Athletes demonstrated resting bradycardia (44 ± 8 vs. 68 ± 14 beats/min, <i>P</i> < 0.001), through an extended ejection time (296 ± 38 vs. 247 ± 30 ms, <i>P</i> < 0.001) and diastolic filling (811 ± 229 vs. 560 ± 161 ms, <i>P</i> = 0.005). Preexercise cardiac outputs were matched (<i>P</i> = 0.969). During exercise, there was a significant group × exercise interaction for left ventricular (LV) ejection time (<i>P</i> < 0.001) and diastolic period (<i>P</i> < 0.001), indicating distinct athletic adaptations. Although the systolic-to-diastolic (S/D) ratio was similar at rest, a significant interaction occurred during exercise (<i>P</i> = 0.013). Athletes also achieved a greater cardiac output response (group × exercise interaction: <i>P</i> < 0.001). Indexed stroke volume increased similarly in both groups (interaction: <i>P</i> = 0.271) yet remained significantly higher in athletes (group effect: <i>P</i> < 0.001). Consequently, athletes maintained superior absolute volumes throughout the protocol, resulting in greater high-intensity stroke volumes. Athletes are able to produce greater reductions in both LV ejection and diastolic filling time and generate higher stroke volumes during exercise, permitting greater cardiac outputs and a greater exercise response.<b>NEW & NOTEWORTHY</b> This study reveals that endurance athletes' slow resting heart rates provide additional time for ventricular filling. During intense exercise, athletes compensate for dramatically shortened filling times by achieving remarkably higher flow rates, particularly during systole. These differences allow athletes to maintain larger stroke volumes at both rest and at high heart rates, producing superior cardiac outputs and highlighting a key physiological mechanism underlying endurance performance.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1423-H1432"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519658","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}