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

{"title":"CCR2⁺ monocyte-derived macrophages drive cardiac hypertrophy in early HFpEF.","authors":"Jana Raman, Steven Simmonds, Ellen Caluwé, Rick van Leeuwen, Caroline Walschap, Mathias Stroobants, Ümare Cöl, Petra Vandervoort, Stephane Heymans, Elizabeth A V Jones","doi":"10.1152/ajpheart.00022.2025","DOIUrl":"10.1152/ajpheart.00022.2025","url":null,"abstract":"<p><p>Heart failure with preserved ejection fraction (HFpEF) is a chronic syndrome driven by systemic inflammation. Resident and monocyte-derived macrophages play opposing roles in several heart diseases. Though general ablation of macrophages has previously been studied in HFpEF, the individual contribution of these subsets to HFpEF development is unknown. We induced preclinical HFpEF in mice using a model consisting of a high-fat diet, chronic low-dose angiotensin II administration, and salt-supplemented drinking water. Our model was marked by circulating Ly6C^hi monocytosis and elevated proinflammatory C-C motif chemokine receptor 2 (CCR2⁺) macrophage infiltration at the expense of the cardioprotective TIMD4⁺ resident macrophage subset. Beyond an inflammatory signature typical of HFpEF, the mouse model also faithfully recreates cardiac fibrosis, hypertrophy, and functional changes in the heart as measured by echocardiography and pressure-volume loops. The experimental mice also show exercise intolerance. Using a loss-of-function genetic model, we found that CCR2 ablation prevented classical macrophage infiltration and improved the resident TIMD4⁺ macrophage representation early in HFpEF development. CCR2^-/- mice showed a higher accumulation of dysfunctional mitochondria in the heart with diffusely organized cristae without worsened mitochondrial fusion (Mitofusin2) or functioning in general (translocase outer membrane, TOM20). Loss of CCR2 did prevent left ventricle (LV) hypertrophy in our preclinical model but it did not resolve the cardiac fibrosis or diastolic dysfunction. Mitochondrial damage has been suggested to drive hypertrophy, however, we found that preventing classical macrophage recruitment increased the presence of damaged mitochondria, even though hypertrophy is resolved. In the future, our results can contribute to successful therapeutic immunomodulation to tackle HFpEF, if combined with antifibrotic treatment.<b>NEW & NOTEWORTHY</b> Development of a multi-comorbidity model induces early heart failure with preserved ejection fraction (HFpEF) in male mice. Early HFpEF is marked by circulating proinflammatory monocytosis (Ly6C^hi) and a disruption in the balance between monocyte-derived macrophage infiltration (CCR2⁺) and resident macrophages (TIMD4⁺). Ablation of CCR2, which prevents recruitment of classical macrophages, improves left ventricle (LV) hypertrophy in early HFpEF but not cardiac fibrosis or diastolic dysfunction. Anti-inflammatory therapies alone, without antifibrotic treatment, will likely not prevent the development of HFpEF.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H109-H123"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148868","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":"Multi-omics analyses of the complex interplay between genetic variants, DNA methylation, and gene expression in COVID-19.","authors":"Guanjie Chen, Lisa DeRoo, Gabriel Goodney, Ayo P Doumatey, Jie Zhou, Adebowale A Adeyemo, Charles N Rotimi, Amadou Gaye","doi":"10.1152/ajpheart.00206.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00206.2025","url":null,"abstract":"<p><p><b>Background:</b> SARS-CoV-2, which drove the 2019 COVID-19 pandemic, continues to engender inquiries into the role of host genetic factors in disease susceptibility. Despite the identification of over 1,000 genes potentially associated with SARS-CoV-2 and COVID-19, the mechanisms connecting genetic variants to phenotype remain elusive. To shed light on these mechanisms, we undertook an integrated analysis, merging data from whole-genome association analyses of COVID-19 with methylome and transcriptomic. <b>Methods:</b> Study includes African American adults from the GENE-FORECAST study, encompassing 371 individuals with whole genome sequencing (WGS), 203 with DNA methylation, and 321 with RNA sequencing (RNA-Seq) of blood. 53.3% of participants reported COVID-19. Significant loci associated with COVID-19 were examined within the framework of methylation quantitative trait loci (mQTL) which located near the gene-of-original (<i>cis</i>-mQTL) and expression quantitative trait loci (eQTL) which located near the gene-of-origin (<i>cis</i>-eQTL), enabling analysis to assess mediators between genetic variants and COVID-19 status. <b>Results:</b> Our analysis identified four intronic variants and confirmed a missense variant, rs1052067, in <i>PMF1</i> associated with COVID-19. Causal mediation analysis revealed that the combination of genetic variants within <i>PMF1</i>, epigenomics, and transcriptomics mapped four pathways influencing COVID-19 status. These pathways include: rs9659072 -> DNAm at chr1:156285845 (annotated to <i>TMEM79</i>) -> ENSG00000198715:13 (annotated to <i>GLMP</i>); rs12083543 -> DNAm at chr1:155951748 (<i>ARHGEF2</i>) -> ENSG00000198715:13 (<i>GLMP</i>); rs1052067 -> DNAm at chr1:155951748 (<i>ARHGEF2</i>)-> ENSG00000198715:13 (<i>GLMP</i>); rs1543294 -> ENSG00000198715:13 (<i>GLMP</i>) -> DNAm at chr1:156077518 (<i>MEX3A</i>). <b>Conclusions:</b> Through integrated multi-omics analyses, we identified genetic variants whose effects on COVID-19 susceptibility are mediated by changes in DNA methylation and mRNA expression. These findings offer insights into potential mechanistic pathways that merit further exploration.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537782","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 dysfunction in chronic kidney disease: a clinical perspective.","authors":"Monique E Cho, Vienna E Brunt, Yan-Ting Shiu, Kanokwan Bunsawat","doi":"10.1152/ajpheart.00908.2024","DOIUrl":"10.1152/ajpheart.00908.2024","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a progressive, multisystemic disorder that augments the risks of cardiovascular (CV) morbidity and mortality as kidney function declines. The endothelium plays a key role in modulating vascular tone, integrity, and homeostasis by producing and releasing a variety of endothelium-derived relaxing factors, including nitric oxide (NO). Endothelial dysfunction is a salient pathogenic mechanism underlying the development and progression of CKD and is characterized by reduced production of vasodilators and increased production of vasoconstrictors (e.g., endothelin-1). Factors such as the uremic milieu, inflammation, and oxidative stress are putative contributors of endothelial dysfunction and reduced NO bioavailability that ultimately impact functional and structural integrity of the vasculature. Because endothelial dysfunction is an independent predictor of CV morbidity and mortality in patients with CKD, several clinical studies have examined disease-related changes in endothelium-dependent vasodilation across the arterial tree. This review will focus on the clinical evidence regarding CKD-associated endothelial dysfunction involving both the micro- and macrovasculature, briefly discussing underlying physiological mechanisms, and summarizing available and emerging pharmacotherapies along with a brief summary of exercise training as a lifestyle intervention.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H135-H153"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148870","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":"Women's cardiovascular health at risk: an urgent call to protect the US biomedical research system and prevent setbacks in women's health research.","authors":"Styliani Goulopoulou, Donna Santillan, Juli Unternaehrer","doi":"10.1152/ajpheart.00182.2025","DOIUrl":"10.1152/ajpheart.00182.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H282-H289"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101170","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":"From the operating room to the bench: use of reverse translation to identify targets in aortic aneurysm.","authors":"Rashi Purohit, Julie K Freed","doi":"10.1152/ajpheart.00304.2025","DOIUrl":"10.1152/ajpheart.00304.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H169-H171"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075521","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":"Repetitive remote ischemic preconditioning as a potential alternative intervention to attenuate arterial stiffness in individuals with elevated blood pressure.","authors":"Money Ghimire, Brittany K Sanchez, Jahyun Kim","doi":"10.1152/ajpheart.00299.2025","DOIUrl":"10.1152/ajpheart.00299.2025","url":null,"abstract":"<p><p>Elevated blood pressure (BP) is associated with increased arterial stiffness and risk of cardiovascular diseases (CVDs). Remote ischemic preconditioning (RIPC) involves three or four cycles of limb blood flow blockage followed by reperfusion with occlusion pressure between 200 and 220 mmHg and has been shown to improve vascular function. However, studies in normotensive adults showed no change in arterial stiffness, possibly due to shorter intervention periods (<1 wk). Therefore, the purpose of this study was to investigate the effects of 4 wk of RIPC on arterial stiffness in adults with elevated BP or stage 1 hypertension (EBP), and whether superoxide dismutase (SOD) levels account for this effect. We hypothesized that 4 wk of RIPC attenuates arterial stiffness measured by carotid-femoral pulse wave velocity (PWV) in individuals with EBP due to SOD upregulation. Young adults with normal blood pressure (NBP) (<i>n</i> = 11, 3 M/8 F, age = 21.0 ± 1.3 yr, BP = 102 ± 7/68 ± 4 mmHg) and EBP (<i>n</i> = 11, 8 M/3 F, age = 21.6 ± 1.6 yr, BP = 124 ± 6/78 ± 6 mmHg) underwent 4 wk of RIPC intervention, and the results showed that RIPC reduced PWV in the elevated BP group (5.66 ± 0.99 vs. 5.34 ± 0.77 m/s, <i>P</i> = 0.037). Furthermore, serum SOD activity was increased in EBP group after RIPC (13.18 ± 3.60 vs. 14.59 ± 4.02 units/mL, <i>P</i> = 0.016) with no significant changes in the normotensive group (<i>P</i> = 0.603). Thus, RIPC may serve as a potential alternative intervention to attenuate arterial stiffness likely via antioxidant upregulation in individuals with EBP.<b>NEW & NOTEWORTHY</b> Repeated RIPC attenuates arterial stiffness in the elevated or stage 1 hypertensive young adults but not in normotensive young adults. Increased SOD activity with repeated RIPC may explain the attenuated arterial stiffness in this population. These results underscore the potential of RIPC intervention to lower CVD risk through reductions in arterial stiffness and blood pressure in healthy young adults with elevated or stage 1 hypertensive blood pressure.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H172-H177"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186265","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":"Evolving hemodynamics in Fontan circulation: age-driven insights in patients with interrupted inferior vena cava and hepatoazygos shunt.","authors":"Vikas Kannojiya, Akshita Sahni, Emily Eickhoff, Neha Zacharia, Nicole St Clair, Noah Schulz, Peter E Hammer, Pedro J Del Nido, Rahul H Rathod, David M Hoganson, Vijay Govindarajan","doi":"10.1152/ajpheart.00072.2025","DOIUrl":"10.1152/ajpheart.00072.2025","url":null,"abstract":"<p><p>Patients with interrupted inferior vena cava (I-IVC) and azygos continuation who undergo Fontan completion via hepatoazygos shunting exhibit unique hemodynamic challenges. This study evaluates age-related shifts in systemic venous return dominance, hepatic flow distribution (HFD), power loss (PL), and flow disturbances using patient-specific computational fluid dynamics (CFD). Data analysis from 95 patients with I-IVC showed a nonlinear shift in upper-to-lower body systemic flow dominance with ratios of 2, 1, and 0.5 (correlating to ages ∼3, ∼10, and ∼20, respectively). CFD simulations for 17 selected patients revealed a trend of increasing HFD toward the right pulmonary artery, with median splits of 45%-49%, 48%-52%, and 40%-60% for the respective flow ratios. Power loss increased significantly with lower-body flow dominance. Median values for absolute PL were 4.75 mW (ratio 2), 16.5 mW (ratio 1), and 33.7 mW (ratio 0.5). Indexed PL showed a similar trend, rising from 0.04 mW/m² to 0.11 mW/m² across the flow ratios. Vorticity and viscous dissipation rates, key metrics of flow disturbances, also increased with lower-body flow dominance, showing strong correlations with PL (<i>R</i> = 0.58-0.76). Kruskal-Wallis-based statistical analysis identified significant statistical differences in absolute PL (<i>P</i> = 0.0045) and flow disturbances (<i>P</i> < 0.001), emphasizing the impact of age-related flow dynamics on Fontan efficiency. Our findings emphasize the need for targeted interventions in patients with I-IVC with azygos continuation to mitigate evolving hemodynamic inefficiencies and optimize Fontan outcomes during critical growth periods.<b>NEW & NOTEWORTHY</b> Evaluate how age-driven changes in patients with interrupted inferior vena cava impact Fontan efficiency. Using patient-specific computational fluid dynamics, our study reveals nonlinear flow dynamics, increasing power loss, and evolving hepatic flow distribution, emphasizing the need for tailored interventions to optimize outcomes.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H124-H134"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965405","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":"Corrigendum for Warrington et al., volume 327, 2024, p. H221-H241.","authors":"","doi":"10.1152/ajpheart.00060.2024_COR","DOIUrl":"10.1152/ajpheart.00060.2024_COR","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"329 1","pages":"H209"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482850","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":"On a heart failure and skeletal muscle axis.","authors":"Jens P Goetze, Dijana Terzic","doi":"10.1152/ajpheart.00385.2025","DOIUrl":"10.1152/ajpheart.00385.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H215-H216"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265051","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":"Novel biomarkers in cardio-oncology: from promise to practice through prospective study.","authors":"Caitlin F Bell, Zachary S Clayton","doi":"10.1152/ajpheart.00338.2025","DOIUrl":"10.1152/ajpheart.00338.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H210-H212"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092332","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}