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

{"title":"What frozen human hearts can tell us about treating heart failure.","authors":"Rhiannon Q Crawford, Helene Tigro, Christopher Solís","doi":"10.1152/ajpheart.00758.2024","DOIUrl":"10.1152/ajpheart.00758.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666833","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":"Predictive value of triglyceride-glucose index for the evaluation of coronary artery disease severity and occurrence of major adverse cardiovascular events.","authors":"Orlando Siverio-Morales, Carmen Mora-Fernández, Carolina Hernández-Carballo, Ernesto Martín-Núñez, Ainhoa González-Luis, Alberto Martín-Olivera, Juan F Navarro-González, Javier Donate-Correa","doi":"10.1152/ajpheart.00684.2024","DOIUrl":"10.1152/ajpheart.00684.2024","url":null,"abstract":"<p><p>The triglyceride-glucose (TyG) index has been proposed as an independent predictor of coronary artery disease (CAD). In this retrospective study we further examine this association and its utility as a predictor for major adverse cardiovascular events (MACE). A total of 870 patients who underwent coronary angiography between May 2008 and June 2009 were included in this retrospective study. The TyG index was calculated using the formula Ln (fasting TG [mg/dL] × FBG [mg/dL]/2). The association of TyG index with the presence and severity of CAD, cardiovascular risk factors, and inflammatory markers was evaluated at baseline. In the longitudinal study, the multivariate adjusted Cox hazard model was used to investigate the associations of the TyG index with the occurrence of MACE during a 5-year follow-up, which was defined as endpoint. The TyG index was significantly associated with the presence and severity of CAD. Multiple linear regression analysis showed that a high TyG index, together with inflammatory markers and dyslipidemia, were independently associated with greater stenotic occlusion of coronary arteries (adjusted R² = 0.031, <i>p</i><0.001). Kaplan-Meier survival curve (free of MACE) by tertiles of the TyG index showed a higher incidence of MACE in the upper tertile (log-rank test, <i>p</i> = 0.02). Multivariate Cox analysis demonstrated that the risk of incident MACE during the follow-up was associated with higher levels of TyG index, even after adjusting for inflammatory parameters and cardiovascular risk factors: hazard ratio (HR), 1.54 (95% confidence interval 1.18-2.13; <i>p</i><0.01). We conclude that elevated TyG index is independently associated with a higher risk of CAD and a poor prognosis for MACE.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666815","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":"Impaired endothelial function contributes to cardiac dysfunction - role of mitochondrial dynamics.","authors":"Cristhian A Gutierrez-Huerta, Giovanni Quiroz-Delfi, Fathima Dhilhani Mohammed Faleel, Andreas Beyer","doi":"10.1152/ajpheart.00531.2024","DOIUrl":"10.1152/ajpheart.00531.2024","url":null,"abstract":"<p><p>The endothelial microvasculature is essential for the regulation of vasodilation and vasoconstriction, and improved functioning of the endothelium is linked to improved outcomes for individuals with coronary artery disease (CAD). People with endothelial dysfunction exhibit a loss of NO-mediated vasodilation, achieving vasodilation instead through mitochondria-derived H₂O₂. Mitochondrial dynamics is an important autoregulatory mechanism that contributes to mitochondrial and endothelial homeostasis and plays a role in formation of reactive oxygen species (ROS), including H₂O₂. Dysregulation of mitochondrial dynamics leads to increased ROS production, decreased ATP production, impaired metabolism, activation of pathological signal transduction, impaired calcium sensing, and inflammation. We hypothesize that dysregulation of endothelial mitochondrial dynamics plays a crucial role in the endothelial microvascular dysfunction seen in individuals with CAD. Therefore, proper regulation of endothelial mitochondrial dynamics may be a suitable treatment for individuals with endothelial microvascular dysfunction and we furthermore postulate that improving this microvascular dysfunction will directly improve outcomes for those with CAD.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666812","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":"Characterization of a novel ovine model of hypertensive heart failure with preserved ejection fraction.","authors":"Joshua W-H Chang, Siyi Chen, Charlotte Hamilton, Julia Shanks, Mridula Pachen, Audrys Pauza, Bindu George, Rohit Ramchandra","doi":"10.1152/ajpheart.00548.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00548.2024","url":null,"abstract":"<p><p>The lack of animal models which accurately represent heart failure with preserved ejection fraction (HFpEF) has been a major barrier to the mechanistic understanding and development of effective therapies for this prevalent and debilitating syndrome characterized by multisystem impairments. Herein, we describe the development and characterization of a novel large animal model of HFpEF in older, female sheep with chronic 2-kidney, 1-clip hypertension. At six weeks post-unilateral renal artery clipping, hypertensive HFpEF sheep had higher mean arterial pressure compared to similarly aged ewes without unilateral renal artery clipping (mean arterial pressure = 112.7±15.9 vs 76.0±10.1 mmHg, <i>P</i> < 0.0001). The hypertensive HFpEF sheep were characterized by (i) echocardiographic evidence of diastolic dysfunction (lateral e' = 0.11±0.02 vs 0.14±0.04 m/s, <i>P</i> = 0.011; lateral E/e' = 4.25±0.77 vs 3.63±0.54, <i>P</i> = 0.028) and concentric left ventricular hypertrophy without overt systolic impairment, (ii) elevated directly measured left ventricular end-diastolic pressure (13±5 vs 0.5±1 mmHg, <i>P</i> = 2.1x10^-6), and (iii) normal directly measured cardiac output. Crucially, these hypertensive HFpEF sheep had impaired exercise capacity as demonstrated by their (i) attenuated cardiac output (<i>P</i> = 0.001), (ii) augmented pulmonary capillary wedge pressure (<i>P</i> = 0.026), and (iii) attenuated hindlimb blood flow (<i>P</i> = 3.4x10^-4) responses, during graded treadmill exercise testing. In addition, exercise renal blood flow responses were also altered. Collectively, our data indicates that this novel ovine model of HFpEF may be a useful translational research tool since it exhibits similar and clinically relevant impairments as that of HFpEF patients.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638551","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":"Perivascular fat is where its at: fat-derived chemerin regulates aortic function in a sex-dependent manner.","authors":"Lisa A Cassis","doi":"10.1152/ajpheart.00749.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00749.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612482","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":"Postnatal development of human atrial cardiomyocytes: linking atrial gene expression profiles and atrial electrophysiology.","authors":"Elise Rougier, Akshata Dhumal, Robert A Rose","doi":"10.1152/ajpheart.00754.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00754.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602851","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 Multifaceted Roles of Red Blood Cells in Health and Disease.","authors":"Helmut Raphael Lieder","doi":"10.1152/ajpheart.00739.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00739.2024","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602857","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":"Averaged Oxygen Desaturation Improves the Prognostic Value of the Six-Minute Walk Test in Elderly Patients with Heart Failure.","authors":"Isamu Sunayama, Kyung-Duk Min, Yoshiyuki Orihara, Junichi Ono, Yuki Matsumoto, Aika Daimon, Yuko Soyama, Eri Manabe, Makiko Oboshi, Kohei Azuma, Masataka Sugahara, Akiyo Eguchi, Yoshiro Naito, Shinichiro Suna, Masanori Asakura, Masaharu Ishihara","doi":"10.1152/ajpheart.00578.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00578.2024","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) is a major cause of hospitalization, and exercise capacity is a key prognostic marker. The six-minute walk test (6MWT) is widely used to assess exercise capacity, but six-minute walk distance (6MWD) varies among individuals, especially the elderly.</p><p><strong>Aim: </strong>This study aimed to assess the hypothesis that ΔSpO₂-Ex, the average oxygen desaturation during the 6MWT, could enhance the prognostic value of 6MWD in elderly HF patients for cardiovascular risk prediction.</p><p><strong>Methods: </strong>In this single-center, prospective observational study, 55 patients aged ≥ 65 years with acute HF were evaluated before discharge. Patients were divided into small and large ΔSpO₂-Ex groups and short and long 6MWD groups based on cut-off values of 6.7% and 220 m, respectively, obtained from the Receiver Operating Characteristics curve analysis. Patients were followed for one year to assess major adverse cardiovascular events, including rehospitalization for heart failure or cardiovascular death.</p><p><strong>Results: </strong>The mean ΔSpO₂-Ex was 5.8 ± 4.3%, and the mean 6MWD was 237.5 ± 106.7 m. Patients with large ΔSpO₂-Ex had significantly higher event rates (HR 6.66, p < 0.001), while those with short 6MWD had HR of 2.40 (p = 0.03). Combining ΔSpO₂-Ex with 6MWD improved predictive accuracy (AUC 0.78) compared to either marker alone (AUC 0.72 for ΔSpO₂-Ex and 0.62 for 6MWD). Importantly, patients with both large ΔSpO₂-Ex and short 6MWD had the highest event rates, indicating the additive prognostic value of combining both markers.</p><p><strong>Conclusion: </strong>ΔSpO₂-Ex is a complementary marker to 6MWD, improving risk stratification in elderly HF patients.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602848","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":"Hypoxia-inducible factor-2α enhances neutrophil survival to promote cardiac injury following myocardial infarction.","authors":"Enzo B Piccolo, Zhi-Dong Ge, Mallory E Filipp, David P Sullivan, Edward B Thorp, Ronen Sumagin","doi":"10.1152/ajpheart.00392.2024","DOIUrl":"10.1152/ajpheart.00392.2024","url":null,"abstract":"<p><p>Heart failure is a major cause of mortality following myocardial infarction. Neutrophils are among the first immune cells to accumulate in the infarcted region. Although beneficial functions of neutrophils in heart injury are now appreciated, neutrophils are also well known for their ability to exacerbate inflammation and promote tissue damage. Myocardial infarction induces hypoxia, where hypoxia-inducible factors (HIFs) are activated and play critical roles in cellular functions. In this context, the role of <i>Hif2α</i> in neutrophils during myocardial infarction is unknown. Here, we demonstrate that neutrophil <i>Hif2α</i> deletion markedly attenuates myocardial infarct size, improves cardiac function, reduces neutrophil survival and tissue accumulation, and correlates with increased macrophage engulfment rates. Mechanistic studies revealed that <i>Hif2α</i> promotes neutrophil survival through binding to hypoxia response element (HRE) in the promoter region of <i>Birc2</i> to regulate expression of the prosurvival factor, cellular inhibitor of apoptosis protein-1 (cIAP1). Inhibition of cIAP1 in neutrophils using the pharmacological agent, Birinapant resulted in increased cell death, establishing a critical role of cIAP1 downstream of <i>Hif2α</i> in neutrophil survival. Taken together, our data demonstrate a protective effect of <i>Hif2α</i> deletion in neutrophils on cardiac injury outcomes through modulation of neutrophil cell survival.<b>NEW & NOTEWORTHY</b> <i>Hif2α</i> in neutrophils increases infarct size, cardiac dysfunction, and ventricular scar after myocardial infarction. <i>Hif2α</i> in neutrophils supports neutrophil survival via cIAP-1 signaling and delays macrophage engulfment.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1230-H1243"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11559636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339447","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":"Red blood cells as potential materials for microRNA biomarker study: overcoming heparin-related challenges.","authors":"Eftychia Kontidou, Rawan Humoud, Ekaterina Chernogubova, Michael Alvarsson, Lars Maegdefessel, Aida Collado, John Pernow, Zhichao Zhou","doi":"10.1152/ajpheart.00609.2024","DOIUrl":"10.1152/ajpheart.00609.2024","url":null,"abstract":"<p><p>microRNAs (miRNAs) have been intensively studied as valuable biomarkers in cardiometabolic disease. Typically, miRNAs are detected in plasma or serum, but the use of samples collected in heparinized tubes is problematic for miRNA studies using quantitative PCR (qPCR). Heparin and its derivatives interfere with qPCR-based analysis, leading to a substantial reduction or even complete loss of detectable miRNA levels. Given that red blood cells (RBCs) express abundant miRNAs, whose expression is altered in cardiometabolic disease, RBCs could serve as an attractive alternative in biomarker studies. Here, we aim to explore the stability of miRNAs in RBCs collected from whole blood with different anticoagulants and thereby the potential of RBCs as alternative materials for miRNA biomarker studies. miRNA profiling was performed in human RBCs via RNA sequencing, followed by qPCR validation of selected miRNAs in RBCs and plasma in both heparinized and EDTA tubes. RNA sequencing revealed abundant miRNA presence in RBCs isolated from blood collected in EDTA tubes. miR-210-3p, miR-21-5p, miR-16-5p, and miR-451a were detected at comparable levels in RBCs isolated from both heparinized and EDTA tubes but not in plasma from heparinized tubes. Of note, miR-210-3p levels were consistently lower in RBCs from individuals with type 2 diabetes compared with healthy controls, regardless of anticoagulant type, supporting their potential as biomarker materials. In conclusion, RBCs offer a promising alternative for miRNA biomarker studies, overcoming heparin-related challenges.<b>NEW & NOTEWORTHY</b> microRNAs are valuable biomarkers in cardiometabolic disease, but heparinized tubes hinder their detection because of qPCR interference. RBCs, which express abundant microRNAs like miR-210-3p, may serve as an alternative. microRNAs, including miR-210-3p, are consistently detectable in RBCs at comparable levels between heparinized and EDTA tubes. miR-210-3p levels in RBCs are similarly reduced in heparinized tubes of patients with type 2 diabetes. Thus, RBCs offer a promising solution for miRNA biomarker studies, overcoming heparin-related challenges.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1296-H1302"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456047","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}