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

{"title":"ET(-1) phone home: a commentary on the complexities of cardiovascular disease risk in postmenopausal women.","authors":"Kyle J Kastrup, Lyndsey E DuBose","doi":"10.1152/ajpheart.00345.2025","DOIUrl":"10.1152/ajpheart.00345.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H89-H90"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186264","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":"High-fat feeding has sex-dependent effects on the structure and biomechanical properties of cerebral parenchymal arterioles and cognitive function.","authors":"Jessica T Yen, Theresa A Landsell, Erinn Laimon-Thomson, Martina Yen, William F Jackson, Anne M Dorrance","doi":"10.1152/ajpheart.00295.2024","DOIUrl":"10.1152/ajpheart.00295.2024","url":null,"abstract":"<p><p>One-third of dementia cases could be prevented by correcting modifiable risk factors, including obesity caused by consuming a high-fat (HF) diet consumption. Dementia is associated with white matter injury, which is associated with impaired cerebral parenchymal arteriole (PA) function. Yet, the impact of HF feeding on PAs remains understudied. We tested the hypothesis that HF feeding would result in structural and biomechanical remodeling of the PAs from male and female rats. We also proposed that HF feeding would impair endothelium-dependent dilation and that these changes would be associated with cognitive decline and neuroinflammation. Three-week-old male and female Sprague-Dawley rats were fed a control or HF diet for 20-24 wk. HF feeding increased body weight and blood pressure in both sexes but caused hyperglycemia only in females. Pial artery blood flow was unchanged by HF feeding in both sexes. The PAs from HF-fed females exhibited inward remodeling; PAs from males were not remodeled but were less distensible. Endothelial function and myogenic tone generation in the PAs were not impacted by HF feeding in either sex. The changes observed in the males were associated with impaired spatial memory and reduced cerebral myelin basic protein expression. HF feeding increased the number of microglia in both sexes, but soma size was only increased in the males. These data suggest that HF feeding impairs cognitive function in males, which is associated with increased stiffness in PAs and increased microglial hypertrophy, whereas HF-fed females remain cognitively normal despite exhibiting significant PA remodeling.<b>NEW & NOTEWORTHY</b> Female rats fed a high-fat diet exhibited inward remodeling of the cerebral parenchymal arterioles; this structural change did not impact cerebral blood flow or cognition. In males, parenchymal arterioles from high-fat fed rats were less distensible; this biomechanical change was associated with cognitive decline and neuroinflammation but not cerebral hypoperfusion. Endothelial function was not impacted by high-fat feeding in either sex. These studies suggest that the pathophysiology of obesity-associated dementia differs between the sexes.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1-H15"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968052","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 novel assessment of anthracycline-induced cardiotoxicity: topological flow data analysis in childhood cancer survivors.","authors":"Tatsuki Nishiyama, Ken Takahashi, Yusuke Akatsuka, Hirohisa Kago, Azusa Akiya, Yu Hosono, Sachie Shigemitsu, Akinori Yaguchi, Osamu Tomita, Junya Fujimura, Masahiro Saito, Keiichi Itatani, Takashi Sakajo, Hiromichi Shoji","doi":"10.1152/ajpheart.00136.2025","DOIUrl":"10.1152/ajpheart.00136.2025","url":null,"abstract":"<p><p>Anthracycline chemotherapy improves survival rates in childhood cancer patients but poses a significant risk of late-onset cardiotoxicity, potentially leading to cardiac dysfunction and heart failure. Recently, flow dynamics parameters derived from two-dimensional fluid dynamics may be sensitive indicators of cardiac dysfunction. Topological flow data analysis (TFDA) mathematically defines vortical flow structures and offers a novel approach to cardiac function assessment. This study aimed to use TFDA to analyze the left ventricular flow patterns in 90 childhood cancer survivors (CCSs) treated with anthracyclines (median age 15.1 yr) and 90 age-matched control subjects. The TFDA parameters, including vortex number, size, circulation, width of mitral inflow, and saddle points, were calculated and compared across the three age subgroups: <i>C1</i> (4-12 yr), <i>C2</i> (13-19 yr), and <i>C3</i> (20-36 yr). The CCSs in <i>group C3</i> exhibited a reduced left ventricular ejection fraction within the normal range, and the longitudinal strain decreased in <i>groups C2</i> and <i>C3</i>. Regarding TFDA parameters, the number of abnormal vortices in the early diastolic frames increased across all CCSs, with significant reductions in the width of the effective mitral inflow in <i>groups C2</i> and <i>C3</i>. Systolic circulation was reduced across all CCSs, and diastolic circulation was decreased in <i>groups C2</i> and <i>C3</i>, which correlated with age, time since chemotherapy, and cumulative anthracycline dose. TFDA parameters identified cardiac dysfunction before conventional echocardiographic markers, highlighting its potential as a novel and sensitive tool for the early detection and long-term monitoring of cardiotoxicity in CCSs and supporting its integration into clinical practice.<b>NEW & NOTEWORTHY</b> This study suggests that topological flow data analysis (TFDA) is a novel and sensitive method for assessing cardiotoxicity in childhood cancer survivors. By analyzing vortical flow parameters, including circulation and abnormal vortices, TFDA detected anthracycline-induced cardiotoxicity earlier than conventional echocardiographic indicators. The findings reveal age- and dose-dependent cardiac dysfunction, emphasizing TFDA's potential as a highly sensitive tool for long-term cardiovascular monitoring and early intervention in high-risk populations.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H41-H50"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959647","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":"Splenic modulation of the early inflammatory response to regional and global ischemia/reperfusion injury in swine.","authors":"Tyler J Rolland, Emily R Hudson, Luke A Graser, Sumbule Zahra, Daniel Cucinotta, Brian R Weil","doi":"10.1152/ajpheart.00714.2024","DOIUrl":"10.1152/ajpheart.00714.2024","url":null,"abstract":"<p><p>The spleen has been identified as a source of proinflammatory leukocytes mobilized after local ischemic injury in rodents. However, the role of the spleen in the inflammatory response to regional or global ischemia/reperfusion injury (IRI) in larger mammals is unknown. We investigated the spleen's contribution to early IRI-associated inflammation in porcine models of acute reperfused myocardial infarction (AMI) and sudden cardiac arrest (SCA). Swine were randomized to splenectomy (SPLX; <i>n</i> = 15) or sham surgery (SHAM; <i>n</i> = 15) 1 wk before a 75 min coronary occlusion (AMI; <i>n</i> = 6/group) or 8 min of ventricular fibrillation and cardiopulmonary resuscitation (CPR) (SCA; <i>n</i> = 9/group). Hemodynamic assessment and echocardiography were performed before and after IRI, with serial blood sampling to assess leukocyte mobilization and cytokine release. Heart and brain samples were collected for postmortem evaluation of injury and leukocyte infiltration. Early post-IRI leukocyte mobilization, cytokine levels, and leukocyte infiltration were similar between groups in each protocol. After SCA, SHAM animals showed a significant 41 ± 15% increase in hematocrit and 30 ± 12% rise in arterial O₂ content during CPR that was absent after SPLX. These differences persisted for up to 90 min and were associated with prolonged time to return of spontaneous circulation (ROSC) and increased vasopressor support in the SPLX group. Contrary to findings in rodents, the spleen is not required for the early inflammatory response to regional or global IRI in swine. However, splenic erythrocyte mobilization during SCA leads to an increase in arterial O₂ content that is associated with earlier ROSC and reduced reliance on vasopressors during CPR and the postresuscitation period.<b>NEW & NOTEWORTHY</b> Acute reperfused myocardial infarction (AMI) and sudden cardiac arrest (SCA) are characterized by ischemia-reperfusion injury (IRI) and inflammation. Although prior studies implicated the spleen as a primary source of inflammatory leukocytes after regional IRI in rodents, our findings indicate that, in swine, the spleen is not required for leukocyte mobilization after AMI or SCA. However, splenic erythrocyte mobilization during whole body IRI increases arterial oxygen content during CPR and may influence outcomes after SCA.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H16-H31"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955951","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":"Sex-specific modulation of cardiac fibrosis and lipid metabolism by B-vitamins in heart failure with reduced ejection fraction in mice.","authors":"Chloé David, Sonia Deschênes, Gabriel Ichkhan, Caroline Daneault, Isabelle Robillard Frayne, Bertrand Bouchard, Anik Forest, Yan Fen Shi, Marie-Ève Higgins, Martin G Sirois, Jean-Claude Tardif, Mathias Mericskay, Jérôme Piquereau, Matthieu Ruiz","doi":"10.1152/ajpheart.00841.2024","DOIUrl":"10.1152/ajpheart.00841.2024","url":null,"abstract":"<p><p>Despite significant advancements in therapies, heart failure (HF) remains a major health challenge. Women, who are underrepresented in HF research, are particularly in need of effective treatments. B-vitamins are a promising and cost-effective option for improving cardiac function. Our study aimed to investigate the sex-specific effects of B-vitamin supplementation on HF with reduced ejection fraction in mice. Male and female mice underwent transverse aortic constriction (TAC) to induce pressure overload. Four weeks post-TAC, mice were randomized to receive either a standard or a vitamin B-enriched (VitB) diet. We found that in females, but not in males, VitB <i>1</i>) extended survival, <i>2</i>) slowed down the decrease in ejection fraction (EF), and <i>3</i>) improved left ventricular morphology. The observed benefits in females were associated with evidence of improved cardiac and lung fibrosis and lower inflammation. In contrast, in males, VitB treatment did not reduce cardiac and lung fibrosis, whereas inflammation remained active in the myocardium. Regarding the circulating lipidome, disturbances were normalized in females with a specific enrichment in long-chain and polyunsaturated triglycerides (TGs) in response to VitB. Conversely, in males, lipidomic alterations remained under VitB treatment and were characterized by the accumulation of shorter and saturated TG in the circulation and myocardium. These data reveal a sex-specific response to VitB supplementation in HF in the context of pressure overload and point to a differential lipidomic remodeling that is only favorable in females.<b>NEW & NOTEWORTHY</b> This study explores the sex-specific effects of B-vitamin supplementation on heart failure with reduced ejection fraction in mice subjected to pressure overload. Our study found that B-vitamins improved survival rates, cardiac function, and reduced fibrosis in female mice, with favorable lipidomic remodeling characterized by an increase in polyunsaturated triglycerides. In contrast, male mice exhibited persistent inflammation, fibrosis, and unfavorable lipidome remodeling despite the B-vitamin supplementation. These findings underscore the sex-specific benefits of B-vitamins in heart failure, suggesting their potential therapeutic value for women, who remain underrepresented in cardiovascular research.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H69-H86"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960833","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":"Reduced peak pressure gradient in patients with aortic stenosis and type 2 diabetes.","authors":"Kosuke Minai, Kazuo Ogawa, Toshikazu D Tanaka, Makoto Kawai, Jun Yoshida, Keisuke Shirasaki, Ryosuke Itakura, Seigo Yamashita, Tomohisa Nagoshi, Takayuki Ogawa, Michifumi Tokuda, Michihiro Yoshimura","doi":"10.1152/ajpheart.00255.2025","DOIUrl":"10.1152/ajpheart.00255.2025","url":null,"abstract":"<p><p>Diabetes impairs energy metabolism throughout the body, including the heart. However, the clinical effect of diabetes on left ventricular (LV) contractility remains unclear. To address this knowledge gap, we investigated the effect of diabetes on patients with aortic stenosis (AS), a model of increased LV afterload. We analyzed data from 276 consecutive patients with AS who underwent transthoracic surgery, echocardiography, cardiac catheterization, and fasting blood sampling. The peak aortic velocity was determined using continuous-wave Doppler echocardiography, and the peak pressure gradient (peak PG) was calculated using the simplified Bernoulli equation. The aortic valve area (AVA) determined using planimetry risk factors, including age, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR) level, sex, hemoglobin level, hypertension, and dyslipidemia, that influenced the peak PG was examined using regression analysis. Structural equation modeling (SEM) was performed to identify the direct and indirect effects of these variables on the peak PG. SE revealed a significant association between the AVA and peak PG (<i>P</i> < 0.001). The peak PG significantly decreased with higher HbA1c (<i>P</i> < 0.001) and increased with age (<i>P</i> = 0.004). Other factors, including HOMA-IR, sex, hypertension, and dyslipidemia, had no significant effects. AVA decreased significantly with age (<i>P</i> = 0.007) and increased with sex (male) (<i>P</i> = 0.034). Diabetes reduces LV contractility, as evidenced in patients with AS. Insufficient glucose metabolism may contribute to LV dysfunction. Clinically, the severity of AS in patients with diabetes should not be underestimated based on the PG alone.<b>NEW & NOTEWORTHY</b> Diabetes may impair left ventricular (LV) contractility, but clear human evidence remains limited. This study investigated its impact in patients with aortic stenosis (AS), demonstrating that diabetes significantly reduces LV function. Clinically, our findings suggest that relying solely on pressure gradients may underestimate AS severity in patients with diabetes, highlighting the necessity for a more comprehensive assessment to ensure accurate evaluation and management of the disease.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H32-H38"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109401","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":"Bend it like BIN1: how a membrane-curving adaptor protein shapes cardiac physiology.","authors":"Heather C Spooner, Rose E Dixon","doi":"10.1152/ajpheart.00198.2025","DOIUrl":"10.1152/ajpheart.00198.2025","url":null,"abstract":"<p><p>Bridging integrator 1, initially named box-dependent myc-interacting protein-1 (BIN1), and also known as Amphiphysin 2 is a versatile N-BAR protein that plays essential roles in membrane remodeling, protein trafficking, and cellular organization across multiple tissues. Although extensively studied in cancer and Alzheimer's disease, BIN1's critical functions in cardiac physiology and pathology represent an emerging frontier with significant therapeutic implications. This review provides a synopsis of our current understanding of BIN1's structure-function relationships, with particular emphasis on cardiac-specific isoforms and their roles in heart function. We examine how BIN1's various domains-including the membrane-curvature forming and sensing BAR domain, phosphoinositide-binding motif, and SH3 protein-protein interaction domains-orchestrate its diverse cellular functions, from t-tubule growth, microfolding, and anchoring to directed protein trafficking and complex assembly. Recent discoveries highlight BIN1's involvement in cardiac aging and disease, where both deficiency and excess of BIN1 can lead to dysfunction. Notably, BIN1 levels are reduced in heart failure while increasing significantly during cardiac aging, suggesting a bidirectional pathophysiology where both insufficient and excessive BIN1 expression can impair cardiac function. We discuss emerging evidence regarding the role of BIN1 in cardiac pathologies, offering potential therapeutic targets. Understanding BIN1's membrane-shaping capabilities and its roles in organizing excitation-contraction coupling machinery could yield novel therapeutic strategies for addressing cardiac dysfunction in various disease contexts.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H94-H108"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109400","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":"Relative contribution of correcting the diet and voluntary exercise to myocardial recovery in a two-hit murine model of heart failure with preserved ejection fraction.","authors":"Emylie-Ann Labbé, Sara-Ève Thibodeau, Élisabeth Walsh-Wilkinson, Maude Chalifour, Pierre-Olivier Sirois, Juliette Leblanc, Audrey Morin-Grandmont, Marie Arsenault, Jacques Couet","doi":"10.1152/ajpheart.00092.2025","DOIUrl":"10.1152/ajpheart.00092.2025","url":null,"abstract":"<p><p>Using a two-hit murine model of heart failure with preserved ejection fraction (HFpEF), we studied cardiac reverse remodeling (RR) after stopping the causing stress [Angiotensin II (AngII) + high-fat diet (HFD); metabolic and hypertensive stress (MHS)] and then introducing voluntary exercise (VE) and feeding the animals with a low-fat diet. This led to extensive left ventricle (LV) RR. We then studied the relative contribution to RR of only correcting the diet or allowing VE after stopping AngII. We next evaluated myocardial recovery after an extended period (12 wk instead of four) by exposing the animals to a second MHS. Our observations revealed a sex-specific response. Stopping AngII but continuing the HFD blocked RR in females, not males. Correcting the diet or implementing VE normalized most gene markers of LV hypertrophy or extracellular matrix remodeling, irrespective of sex. Twelve weeks of recovery were associated with normal LV morphology and function, except for several abnormal diastolic echocardiographic parameters. A second MHS after these 12 wk led to a loss of ejection fraction in males. The response of females was like that after the first MHS, suggesting a better myocardial recovery. The MHS likely changed myocardial glucose metabolism. Pyruvate dehydrogenase (PDH) activity, which is responsible for pyruvate entry in the mitochondria, was reduced after MHS, and this was accompanied by an increase in PDH phosphorylation and pyruvate dehydrogenase kinase 4 content. RR normalized these. Our results suggest sex-specific RR after stopping the MHS and that myocardial anomalies remaining make males more sensitive to a second HFpEF-inducing stress.<b>NEW & NOTEWORTHY</b> Most new mouse models of heart failure with preserved ejection fraction (HFpEF) are based on the combination of hypertension and metabolic alterations. These models provide a better approximation of the complexity of the processes involved in human HFpEF. Here, we show that the extent of reverse remodeling and myocardial recovery after stopping the causal stress in a mouse model depends on the biological sex, recovery duration, and diet correction.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H51-H68"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148872","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":"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":"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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}