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

{"title":"Racial Disparity in Microvascular Function among Women with Newly Diagnosed Breast Cancer.","authors":"Abigayle B Simon, Jacob Looney, Marsha Blackburn, Reva H Crandall, Jeffrey Thomas, Paul Kellam, McKay Mullen, Avirup Guha, Priyanka Raval, Neal L Weintraub, Ryan A Harris","doi":"10.1152/ajpheart.00323.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00323.2025","url":null,"abstract":"<p><p><b>BACKGROUND:</b> Cardiovascular disease (CVD) is a leading cause of death in women with breast cancer, with non-Hispanic Black (NHB) women experiencing higher CVD-related mortality compared to non-Hispanic White (NHW) women. Differences in vascular health may contribute to this disparity. This study assessed cardiovascular health in NHB and NHW women with breast cancer. <b>METHODS:</b> Forty-five women (25 NHW, 20 NHB) within two years of diagnosis (AJCC stages 0-3) participated. Clinical labs, senescence-associated secretory phenotype (SASP), and allostatic load were assessed. Flow-mediated dilation (FMD) assessed conduit vessel function; cutaneous post-occlusive reactive hyperemia (PORH), local thermal heating (LTH), and iontophoresis of acetylcholine (Ach) assessed microvascular function. Pulse wave velocity (PWV) and pulse wave analysis (PWA) measured arterial and aortic stiffness, respectively. Maximal exercise testing (VO₂ peak) and near-infrared spectroscopy assessed skeletal muscle oxidative capacity (SMOC). <b>RESULTS:</b> Participants enrolled 6±5 months after diagnosis. Chemotherapy exposure (<i>p</i>=0.897) and cancer stage (<i>p</i>=0.382) were not different between groups. NHW women were older (59±12 vs. 53±12 years; <i>p</i>=0.090), but BMI, clinical labs, SASP, and allostatic load did not differ (all <i>p</i>>0.05). NHW women demonstrated higher PORH (<i>p</i><0.001), LTH (<i>p</i><0.001), and Ach responses (<i>p</i>=0.033), which remained significant after adjusting for cancer stage and chemotherapy. No differences were seen in FMD, PWV, PWA, VO₂₂ peak, or SMOC. <b>CONCLUSION:</b> NHB women with breast cancer exhibited impaired microvascular function compared to NHW women, independent of social determinants, cancer stage, or chemotherapy. These findings suggest microvascular dysfunction may contribute to racial disparities in CVD risk after breast cancer diagnosis.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599152","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":"Role of Membrane Microdomains in Cardiac Protection: Strategies for Diabetic Cardiomyopathy.","authors":"Alice E Zemljic-Harpf, Jacqueline A Bonds, Juan Pablo Zuniga Hertz, Hemal H Patel","doi":"10.1152/ajpheart.00139.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00139.2025","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is a cardiac disorder characterized by structural and functional impairments independent of coronary artery disease. Membrane microdomains, including lipid rafts and caveolae, play a crucial role in cardiac signaling, insulin receptor trafficking, and ion channel regulation. In diabetes, disrupting these microdomains leads to impaired insulin signaling, oxidative stress, and mitochondrial dysfunction, exacerbating cardiac pathology. This review explores the role of caveolins and lipid rafts in DCM and how their dysfunction contributes to disease progression. We highlight how therapeutics used to manage diabetic patients may impact microdomain integrity. Future research should focus on targeting membrane microdomains for novel treatments.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599153","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":"Cardiomyocyte YAP represses myocardial inflammation and fibrosis and restrains MEF2 regulated gene expression.","authors":"Van K Ninh, Melissa Barlow, Sidar Aydin, Cameron Servetus Brand, Justin Yu, Jeffrey Smith, Jamie Francisco, Richard Daneman, Kevin Robert King, Shigeki Miyamoto, Dominic P Del Re, Joan Heller Brown","doi":"10.1152/ajpheart.00799.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00799.2024","url":null,"abstract":"<p><p>Cardiomyocyte signaling through the transcriptional co-activator Yes-associated protein (YAP) has been shown to protect the myocardium against ischemic or mechanical stress. Inflammatory responses initiated in cardiomyocytes play a major role in development of cardiac dysfunction. We tested the relationship between YAP and inflammatory gene expression using cardiomyocyte specific YAP-KO mice. WT and KO mice were infused with Angiotensin II (AngII) at 1.5 μg/kg/min and sacrificed 24 hrs or 3 days post infusion. YAP deletion markedly enhanced AngII-induced mRNA expression of pro-inflammatory cytokines and chemokines, a response that occurred selectively within cardiomyocytes. Hearts from YAP-KO mice also had increased F4/80, CD68, and Col1 staining. Single nuclei RNA-sequencing (snRNA-seq) of WT and YAP-KO hearts showed significant upregulation of pro-inflammatory cytokines and of a range of genes including those in the cJun family, CamKIIδ and Tlr4. Isolated cardiomyocytes transfected with YAP siRNA or a constitutively active YAP mutant showed respectively enhanced and decreased cJun, CamkIIδ, and Tlr4 mRNA gene expression. HOMER motif enrichment analysis of differentially expressed genes from the snRNA-seq data revealed that most highly upregulated transcripts in YAP-KO vs WT hearts were enriched in MEF2 binding sites. Western blot analysis of hearts from YAP-KO mice treated with AngII showed increased MEF2C protein compared to WT hearts. MEF2C siRNA transfection diminished the potentiation of gene expression by siYAP in isolated cardiomyocytes, implicating MEF2 as a downstream YAP target. Our findings indicate that activation of cardiomyocyte YAP serves, in part, to repress MEF2 regulated genes and restrain cardiomyocyte inflammation.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599149","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":"NIH Cuts: A Costly Retreat-Defunding Precision Lifestyle Medicine Amid the Cardiovascular-Kidney-Metabolic Crisis.","authors":"Zacharias Papadakis","doi":"10.1152/ajpheart.00353.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00353.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599151","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":"Is a Decline in Myocardial Citrullination in the Aged Female Heart Really PAD 2 the Bone?","authors":"Avery N Kendall, Helen E Collins","doi":"10.1152/ajpheart.00469.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00469.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599150","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-differences in vascular adaptations to exercise training within different intensity domains.","authors":"Letizia Rasica, Erin Calaine Inglis, Rogerio N Soares, Juan M Murias","doi":"10.1152/ajpheart.00261.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00261.2025","url":null,"abstract":"<p><p>Cardiorespiratory fitness (commonly assessed as maximal oxygen consumption, V̇O₂max) is an independent predictor of risk for cardiovascular disease-related mortality. Endurance exercise training is recognized as a clinically validated intervention to significantly increase V̇O₂max, and growing evidence exists demonstrating a tight connection between endurance training intensity domain and changes in V̇O₂max. However, whether the vascular adaptations to exercise training are also influenced by intensity domains is unknown. Also unknown is the potential influence of sex on these responses. Thus, we assessed domain-specific hemodynamic and lower limb vascular adaptations in seventy healthy sedentary adults (35 females and 35 males) that underwent 6 weeks of endurance exercise training within five (n=14 per group; 7 females and 7 males) intensity domains: moderate, MOD; lower heavy intensity, HVY1; upper heavy-intensity, HVY2; high-intensity interval training in the severe domain, HIIT; sprint-interval training in the extreme domain (SIT). We found that: i) HIIT was associated with greater changes in resting hemodynamics (i.e., increased in resting mean arterial pressure and femoral artery vascular conductance) compared to MOD; ii) changes in V̇O₂max were positively associated with changes in resting vascular conductance, femoral artery diameter, and indexes of reactive hyperemia while negatively associated with femoral artery flow-mediated dilation in females; iii) sex-related associations between changes in V̇O₂max and peripheral vascular adaptations were more evident in response to HIIT. Taken together, our findings indicate that peripheral vascular adaptations associated with changes in cardiorespiratory fitness are impacted by sex and the exercise intensity domain within which training is performed.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582815","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 angiotensin II type 2 receptor attenuates aging-associated arterial stiffness in female mice.","authors":"Casey G Turner, Rachel Kenney, Jennifer Vorn, Seung Kyum Kim, Gregory Martin, Lakshmi Pulakat, Iris Z Jaffe, Jennifer J DuPont","doi":"10.1152/ajpheart.00328.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00328.2025","url":null,"abstract":"<p><p>Arterial stiffness is associated with overall and cardiovascular-specific mortality, and this association is exacerbated in women over 55-years-old. Recent literature supports that stimulation of the angiotensin II type 2 receptor (AT2R) can protect from arterial stiffening, and that AT2R has a greater role in female cardiovascular physiology relative to males. The current study aimed to investigate the role of the AT2R in sex differences in aging-associated arterial stiffness. In female mice, the aging-related increase in arterial stiffness is temporally associated with a loss of aortic AT2R mRNA expression, but this is not observed in males. Chronic AT2R inhibition <i>in vivo</i> increases arterial stiffening in young female and male mice, as well as middle-aged female mice. The inhibition of AT2R is associated with an increase in aortic integrinα5 mRNA expression in young males and an increase in collagen1α1 mRNA expression in middle-aged females. Overall, these findings identify a sex-specific mechanism of aging-associated arterial stiffening in mice involving AT2R attenuation and collagen upregulation in females.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582817","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-specific effects of mild kidney dysfunction on vascular function in midlife and older adults.","authors":"Sanna Darvish, McKinley E Coppock, Kevin O Murray, Daniel H Craighead, Michel Chonchol, Kristen L Nowak, Douglas R Seals, Matthew J Rossman","doi":"10.1152/ajpheart.00332.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00332.2025","url":null,"abstract":"<p><p>Mild kidney dysfunction (MKD) increases cardiovascular disease (CVD) risk. Vascular dysfunction, including vascular endothelial dysfunction and aortic stiffening, is a key antecedent to CVD, but the impact of MKD on vascular function in midlife/older (ML/O) adults is not established. Moreover, sex is a biological variable that influences vascular function, but whether sex modulates the effects of MKD on vascular function is unclear. Vascular endothelial function (brachial artery flow-mediated dilation, FMD_BA) and aortic stiffness (carotid-femoral pulse wave velocity, PWV_CF) were compared in 93 ML/O men and postmenopausal women with MKD (estimated glomerular filtration rate [eGFR]: 60-89mL/min/1.73m²) versus 78 ML/O adults without MKD (healthy controls; eGFR: ≥90mL/min/1.73m²) (age: 50+ years). Circulating markers of inflammation and oxidative stress were also assessed. FMD_BA was lower in men with MKD (4.0±0.3%) versus healthy controls (5.5±0.5%; <i>P</i>=0.0097) and correlated with eGFR (r_s=0.30, <i>P</i>=0.0073). There was no difference in FMD_BA between women with MKD (4.7±0.4%) and healthy controls (4.8±0.5%; <i>P</i>=0.86) and no relation with eGFR. PWV_CF was higher in men with MKD (9.4±0.2m/s) versus controls (8.4±0.3m/s; <i>P</i>=0.030) and correlated with eGFR (r=-0.34, <i>P</i>=0.0013). However, PWV_CF was not different between women with MKD (9.3±0.5m/s) and controls (10.1±0.4m/s; <i>P</i>=0.099) and not related to eGFR. The observed effects of MKD on vascular function were independent of traditional CVD risk factors and medication use. There were no differences in markers of inflammation nor oxidative stress between controls and MKD. Our findings suggest that vascular dysfunction may contribute to increased CVD risk associated with MKD in ML/O men but not postmenopausal women.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582816","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":"Exogenous estradiol increases cardiovagal baroreflex sensitivity during a hypertensive stimulus in premenopausal young women.","authors":"Rauchelle E Richey, Jennifer Ann Miner, Jonathon C Miner, Vienna E Brunt, Paul F Kaplan, John R Halliwill, Christopher T Minson","doi":"10.1152/ajpheart.00131.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00131.2025","url":null,"abstract":"<p><p>Women have a greater reduction in cardiovagal baroreflex sensitivity (CVBRS) as they age which contributes to an elevated cardiovascular disease risk. One potential contributor to the attenuated CVBRS may be reductions in estrogen. Therefore, we tested the hypothesis that isolated estradiol (E₂) and combined E₂ and progesterone (P₄) would increase CVBRS to the same extent. To examine the acute effects of E₂ and P₄ on CVBRS in healthy pre-menopausal women, we used a gonadotropin releasing hormone antagonist to suppresses endogenous sex hormones. We tested 29 young adult women over 10-12 days of hormone manipulation. After 4 days of hormone suppression participants were given either 0.1-0.2 mg transdermal estradiol (E₂) or 200 mg oral micronized progesterone (P₄) per day. Following 3-4 days of isolated hormones, combined hormones (200mg of progesterone and 0.1-0.2mg estradiol) were administered. CVBRS was assessed during a modified Oxford protocol approximately 4 days following each change in hormones. Overall CVBRS was determined as the slope of the response between the R-R interval and systolic blood pressure. CVBRS slope during the hypotensive (sodium nitroprusside) and hypertensive (phenylephrine) phases of the modified Oxford were also assessed. There was no change in the overall R-R Interval or hypotensive CVBRS during any of the hormone trials. Interestingly, the E₂ group's CVBRS increased in response to the hypertensive stimulus while the P₄ group had no change. These data suggest that estradiol alone augments CVBRS to a hypertensive stimulus, but progesterone alone and combined E₂ and P₄ do not change CVBRS.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558826","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 two-pore K⁺ channel TREK-1 regulates pressure overload-induced cardiac remodeling.","authors":"Cemantha M L Johnson, Drew M Nassal, Alexander J Winkle, Benjamin Buck, Xianyao Xu, Xiaoping Wan, Mei Han, Simon Lococo, Nicholas Leahy, Shivangi Mohta, Rebecca Shaheen, Omer Cavus, Aaryan Kohli, Yuanyuan Cao, Mona El Refaey, Sakima Smith, Xun Ai, Isabelle Deschênes, Thomas J Hund","doi":"10.1152/ajpheart.00821.2024","DOIUrl":"10.1152/ajpheart.00821.2024","url":null,"abstract":"<p><p>Heart failure (HF) represents a major burden on the healthcare system, with patients with HF at increased risk for a host of comorbidities, including ventricular arrhythmias. Despite considerable advances in defining cell- and organ-level changes associated with HF, the precise mechanisms driving structural and electrical remodeling remain to be defined. We sought to elucidate the role of the two-pore K⁺ channel TREK-1 in cardiac remodeling in pressure overload-induced HF. Cardiac-specific TREK-1 conditional knockout (TREK1cKO) and floxed control mice were subjected to transaortic contraction (TAC) or sham procedure and evaluated for 6 wk by echocardiography and subsurface electrocardiograms. Ventricular myocytes were isolated for action potential, intracellular Ca²⁺, and contractility measurements. The expression/regulation of key cell signaling pathways was evaluated early in remodeling. TREK1cKO and control mice showed a significant decrease in cardiac systolic function with evidence of hypertrophy as early as 2 wk post-TAC compared with sham. However, TREK1cKO mice displayed a more severe decline in function with enhanced left ventricular chamber dilation (eccentric remodeling) compared with control 6 wk post-TAC. Similarly, TAC TREK1cKO mice demonstrated greater prolongation of the QT and QRS intervals compared with TAC control. TAC TREK1cKO ventricular myocytes exhibited greater action potential prolongation with paradoxical improvements in Ca²⁺ homeostasis and contractility compared with control. Two weeks post-TAC, TREK1cKO hearts exhibited elevation of STAT3 phosphorylation at Y705 compared with control. Our findings reveal a complex interaction between chronic stress, TREK-1, STAT3 regulation, and cardiac remodeling, with TREK-1 exerting both maladaptive and protective effects on overall cardiac function.<b>NEW & NOTEWORTHY</b> A major finding of this study is the involvement of the background K⁺ channel TREK-1 in modulating STAT3 activation, profibrotic gene expression, and fibrosis with implications for the cardiac remodeling response to chronic pressure overload.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H178-H190"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092276","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}