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

{"title":"Modeling HFpEF in mice: role of lifestyle interventions and implications for humans with heart failure.","authors":"Evan J Nessen, Jesse D Moreira-Bouchard","doi":"10.1152/ajpheart.00393.2025","DOIUrl":"10.1152/ajpheart.00393.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H206-H208"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265050","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":"Inherited burdens: the cardiac cost of parental obesity in offspring following myocardial infarction.","authors":"Madison D Cooper, Yonggang Ma","doi":"10.1152/ajpheart.00291.2025","DOIUrl":"10.1152/ajpheart.00291.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H91-H93"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957600","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":"Adding insult to injury-myocardial cell death and dysfunction in donor hearts subjected to warm ischemia.","authors":"Oscar van der Have, Karin Tran-Lundmark","doi":"10.1152/ajpheart.00284.2025","DOIUrl":"10.1152/ajpheart.00284.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H39-H40"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956444","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":"Complexome profiling identifies changes in mitochondrial supercomplexes in murine heart failure.","authors":"Claire Fong-McMaster, Ella McIlroy, Michelle M Levesque, Stephanie Myers, Serena M Pulente, Gurrose Gahla, Ilka Lorenzen-Schmidt, Miroslava Cuperlovic-Culf, Arsalan S Haqqani, Erin E Mulvihill, Mary-Ellen Harper","doi":"10.1152/ajpheart.00278.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00278.2025","url":null,"abstract":"<p><p>Heart failure is characterized by metabolic derangements such as altered substrate metabolism and mitochondrial dysfunction. Mitochondrial supercomplexes, which are higher-order molecular structures comprised of multi-subunit complexes of the electron transport chain, are decreased in heart failure. To investigate the supercomplex proteome composition in heart failure, we used an <i>in vivo</i> myocardial infarction (MI) model in which mice exhibited reduced cardiac function, confirmed by two-dimensional echocardiography at 4 weeks post-infarction. To assess proteins within supercomplexes, we used an emerging technique known as complexome profiling. This technique involved separating out mitochondrial protein complexes using Blue-Native PAGE combined with mass spectrometry to identify proteins within supercomplex gel bands. We identified band-dependent decreases or increases in the relative abundance of subunits of the electron transport chain between MI and sham mice. Decreased abundance of proteins involved in α-ketoglutarate dehydrogenase metabolism including DLST was also identified in the supercomplex bands of MI mice compared to sham mice. In addition, decreased abundance of redox-related proteins such as SOD2 and changes in ribosome protein subunits were identified in the MI mitochondria. In conclusion, we identified changes in the mitochondrial supercomplex proteome in a murine model of heart failure, providing insight and novel mechanisms that may be contributing to the metabolic dysfunction in heart failure.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526118","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 splicing factor kinase SRPK1 is a therapeutic target for Peripheral Vascular Disease.","authors":"Sohni Ria Bhalla, Mussarat Wahid, Jason O Amartey, Amira Zawia, Federica Riu, Yizhuo Gao, Jyoti Agrawal, Amy P Lynch, Maria Jc Machado, Tom Hawtrey, Ryosuke Kikuchi, Kathryn R Green, Lydia Teboul, Claire L Allen, Zoe Blackley, Keerthana Rajaji, Jennifer Batson, Steven J Harper, Sebastian Oltean, Winfried Amoaku, Andrew V Benest, Jonathan C Morris, Bruce Braithwaite, David O Bates","doi":"10.1152/ajpheart.00564.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00564.2024","url":null,"abstract":"<p><p><b>Introduction.</b> In peripheral arterial disease (PAD) anti-angiogenic VEGF-A₁₆₅b isoform overexpression in monocytes contributes to impaired collateralisation. Serine-arginine protein-kinase-1 (SRPK1) regulates VEGF splicing. To determine whether SRPK1 controlled monocytic VEGF, impairing collateralisation, we investigated SRPK1 inhibition and monocyte-specific knockout in mouse models of and in human monocytes from PAD. <b>Methods.</b> VEGF-A₁₆₅b activity was measured by co-culture of PAD patients' monocytes with endothelial cells with SRPK1 inhibition. Mice with impaired revascularisation due to soluble-frizzled-related-protein-5 knockout (Sfrp5^-/-), monocyte-specific Wnt5a gain-of-function (LysM-Wnt5a^GOF), or obese mice on a high-fat high-sucrose (HF/HS) diet were subjected to femoral artery ligation and treated with SRPK1 inhibitor. We generated an SRPK1 conditional knockout and crossed it with monocyte-specific (LysM-Cre) driver line to specifically knockout SRPK1 in monocyte lineages. Blood flow was measured by Laser Speckle Imaging before, and for 28 days after surgery. <b>Results.</b> Monocytes from PAD patients significantly inhibited endothelial cell migration, which was reversed by an anti-VEGF-A₁₆₅b antibody. Surprisingly, migration was stimulated by SRPK1 inhibition, switching splicing from VEGF-A₁₆₅b to VEGF-A₁₆₅a. In Sfrp5^-/-, LysM-Wnt5a^GOF and HF/HS mouse models of PAD, blood flow was improved by SRPK1 inhibition. Impaired revascularisation in LysM52 Wnt5a^GOF mice was rescued in LysM-Wnt5a^GOF:SRPK1^MoKO mice, which had a phenotypic shift towards M2 macrophages. Impaired blood flow recovery was also rescued in obese-SRPK1^MoKO mice. <b>Conclusion.</b> VEGF splicing in monocytes is regulated differently from VEGF splicing in epithelial or cancer cells suggesting that control of splicing is dependent on cell type and/or environment. SRPK1 inhibition enhances collateralisation in mice, and in human <i>in vitro</i> models of monocyte-dependent impaired angiogenesis.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526056","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":"Blunted exercise hyperemic response to lower limb exercise in individuals with Down syndrome.","authors":"Sara R Sherman, Ronald E Jackson, Brooks A Hibner, Natalia Salvatierra Lima, Ryan Cloud, Bo Fernhall, Tracy Baynard","doi":"10.1152/ajpheart.00080.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00080.2025","url":null,"abstract":"<p><p><b>Background:</b> Autonomic dysfunction is common in individuals with Down syndrome (DS). Coordination of autonomic function is essential for appropriate peripheral blood flow delivery and blood pressure (BP) regulation during lower limb dynamic exercise. Our purpose was to examine the effects of lower limb dynamic exercise on femoral blood flow (FaBF) and BP to both active and inactive limbs at both relative and absolute intensities in individuals with and without DS. <b>Methods:</b> Twenty-four individuals with DS (24±5yrs; 30.3±6.2kg/m²) and without DS (25±4yrs; 26.5±4.5kg/m²) performed five knee extensions at 10%, 20%, 30% of maximal dynamic power (MDP; relative intensity), 11 Nm and 16 Nm (absolute intensity). FaBF was measured using Doppler ultrasound of both limbs simultaneously. Beat-to-beat mean arterial pressure (MAP) was assessed using finger photoplethysmography. Femoral vascular conductance (FaVC) was calculated: FaBF/MAP. <b>Results:</b> Individuals with DS demonstrated blunted FaBF (~55% lower) and FaVC (~53% lower) in their active limb compared to individuals without DS at all (10%, 20%, 30% of MDP) relative intensity sets (<i>groupXtime</i>, <i>p</i><0.001). Similarly dampened FaBF (~50% lower) and FaVC (~46% lower) were observed during absolute intensities for individuals with DS (<i>groupXtime</i>, <i>p</i><0.001), without group differences in MAP. FaBF and FaVC to the inactive limb were higher during 30% MDP intensity in individuals with DS (<i>groupXtime</i>, <i>p</i>=0.006). <b>Conclusions:</b> These findings suggest individuals with DS are unable to direct BF to working muscles and show an unfavorable increase in inactive limb BF during lower limb exercise. Inadequate muscle perfusion may limit their ability to meet exercise demands and contribute to reduced work capacity.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526117","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":"Vascular Dysfunction in Diabetes and Pharmacotherapeutic Opportunities: A Focus on Endothelial Cell Health.","authors":"Ross A Okazaki, Syed H Rizvi, Rachael Lyons, Leili Behrooz, Naomi M Hamburg","doi":"10.1152/ajpheart.00793.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00793.2024","url":null,"abstract":"<p><p>Endothelial dysfunction contributes to the pathogenesis and progression of type 2 diabetes mellitus (T2DM) and cardiovascular disease. Endothelial dysfunction in T2DM has been studied extensively using in experimental models and human studies using non-invasive assessment of vasomotor function. Recent work has also demonstrated the feasibility of translational research using freshly isolated human endothelial cells (FIHECs) to uncover novel mechanisms of endothelial dysfunction in T2DM. This review provides an overview of the relation between endothelial dysfunction and cardiometabolic disease with an emphasis on novel mechanisms of endothelial dysfunction in T2DM that have been uncovered in FIHECs. We then discuss how FIHECs could be utilized in the assessment of the vascular benefits of current and future therapeutic treatments for patients with T2DM.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526057","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":"Loss of Elmsan1 in Cardiomyocytes Leads to Age-Dependent Cardiac Dysfunction and Reduced Lifespan.","authors":"Meimei Wang, Hui Li, Chaoshan Han, Yunxi Chen, Lihao He, Min Xie, Hind Lal, Vladimir G Fast, Douglas R Moellering, Jianyi Zhang, Rui Lu, Martin Young, Yang Zhou","doi":"10.1152/ajpheart.00810.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00810.2024","url":null,"abstract":"<p><p>Histone deacetylase (HDAC) complexes regulate pathological gene programs during heart disease progression. The recently identified mitotic deacetylase complex (MiDAC), which includes DNTTIP1, ELMSAN1, and HDAC1/2, remains the least characterized among these complexes. ELMSAN1 has been implicated in left ventricular remodeling, and its global deletion in mice leads to heart malformation. To investigate its role in mouse heart, we generated cardiomyocyte-specific <i>Elmsan1</i> knockout (ELM cKO) using αMHC driven Cre recombinase. We analyzed both male and female animals across three experimental groups: αMHC-Cre (Cre control), ELM fl/fl (floxed control) and ELM cKO. In male ELM cKO mice, ejection fraction (EF) was significantly reduced by 12 weeks (45.64±3.12%), compared to αMHC-Cre (55.91±1.29%) and ELM fl/fl (59.16±3.70%) controls. By 24 weeks, EF declined further to 20.79%±4.52, representing a reduction of 46.4% (p<0.01) and 62.1% (p<0.0001) compared to αMHC-Cre and ELM fl/fl mice respectively. The heart failure phenotype in ELM cKO mice was supported by cardiomyocyte hypertrophy morphology, ventricular dilation, and shortened lifespan. Female ELM cKO mice exhibited similar defects with delayed onset. To investigate early molecular changes, we performed RNA sequencing on pre-symptomatic hearts from 8-week-old mice. A total of 1055 genes were differentially expressed in ELM ckO hearts, with 460 upregulated and 595 downregulated. Gene enrichment analysis revealed suppression of tricarboxylic acid cycle and key cardiac genes. These transcriptional changes were accompanied by decreased mitochondrial respiratory chain complex proteins, ultrastructural mitochondrial abnormalities, and impaired calcium handling. Our study demonstrates that Elmsan1 is pivotal for maintaining the heart function and hemostasis with advanced age.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526119","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":"PDE-5 INHIBITION MITIGATES MENTAL STRESS-INDUCED ENDOTHELIAL DYSFUNCTION IN RESISTANT HYPERTENSION.","authors":"Amanda Sampaio Storch, Helena Naly Miguens Rocha, Joao Dario Mattos, Eliza Prodel, Juliana Mentzinger, Gabriel Fernandes Teixeira, Mariana Silva Cytrangulo, Rebeca Lial Rosado, Antonio Cláudio L Nóbrega, Ronaldo Aoc Gismondi, Natalia Galito Rocha","doi":"10.1152/ajpheart.00336.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00336.2025","url":null,"abstract":"<p><p><b>PURPOSE:</b> Resistant hypertension (RH) is associated with an increased risk of adverse cardiovascular events and mental stress (MS) is one of the major risk factors. We aimed to test the hypothesis that a phosphodiesterase 5 inhibitor (iPDE5) would minimize the deleterious effects of MS on the endothelial function of those patients. <b>METHODS:</b> In two experimental days, patients with RH (63±5 years; 30.2±3.1 kg/m²) received iPDE5 (sildenafil citrate; 50 mg) or a placebo (PL) pill, in a randomized, crossover, double-blind, and placebo-controlled clinical trial. After 30 minutes, subjects underwent a five-minute MS task (modified Stroop Color-Word Test). Flow-mediated dilatation (FMD) and blood flow (BF) measurements (vascular ultrasound), pulse wave analysis (applanation tonometry), and blood sampling (for vasoactive substances and cGMP measurements) were performed at baseline, during or immediately after MS and 30 minutes after MS (MS30). <b>RESULTS:</b> BP, heart rate, and BF increased during the MS task in both conditions (p≤0.02 vs. rest). FMD decreased immediately after MS (p<0.01 vs. baseline) and MS30 (p<0.01 vs. baseline) in the PL condition, whereas it was higher in MS (p=0.03 vs. PL) and MS30 (p<0.01 vs. baseline; p=0.04 vs. MS; p <0.01 vs. PL) in the iPDE5 condition. Peripheral and central systolic blood pressures were lower while plasma nitrate and cGMP were higher in the iPDE5 condition throughout the protocol (p≤0.04 vs. rest). <b>CONCLUSION:</b> Present data suggest that iPDE5 prevents MS-induced endothelial dysfunction and improves cardiovascular hemodynamics in RH.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526055","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":"Endothelial Metabolic Zonation in the Vascular Network: A Spatiotemporal Blueprint for Angiogenesis.","authors":"Kesha K Dalal, Venkatesh Katari, Narendra Kondapalli, Sailaja Paruchuri, Charles K Thodeti","doi":"10.1152/ajpheart.00352.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00352.2025","url":null,"abstract":"<p><p>Angiogenesis, a cornerstone of vascular development, tissue regeneration, and tumor progression, is critically orchestrated by the metabolic behavior of endothelial cells (ECs). Recent discoveries have redefined ECs not as metabolically uniform entities, but as spatially and functionally heterogeneous populations whose metabolic states govern their angiogenic potential. This review presents a comprehensive synthesis of metabolic zonation in ECs, spanning arterial, venous, and capillary domains, and highlights cell-type-specific programs during sprouting angiogenesis-including tip, stalk, and phalanx cells. We explore how distinct metabolic pathways-glycolysis, oxidative phosphorylation, fatty acid oxidation, and glutaminolysis-are differentially utilized across tissue contexts such as the brain, skeletal muscle, kidney, and tumor microenvironments. We discuss technological breakthroughs in spatial metabolomics, temporal (circadian) regulation of endothelial metabolism, and emerging clinical strategies to target EC metabolic vulnerabilities in cancer and ischemic diseases. Furthermore, we advocate for spatiotemporal modeling of EC metabolism using computational and machine learning frameworks to predict angiogenic behavior and accelerate therapeutic discovery. This integrative perspective underscores the need for precision-targeted angiogenic interventions and establishes metabolic zonation as a foundational principle in vascular biology.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511429","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}