American journal of physiology. Heart and circulatory physiology最新文献_第4页

Enhanced vascular contraction induced by exposure to angiotensin II mediated by endothelin-1 biosynthesis following PKCβ activation.

IF 4.1 2区医学

American journal of physiology. Heart and circulatory physiology Pub Date : 2025-01-31 DOI: 10.1152/ajpheart.00541.2024

Hirotaka Tajima, Nayu Morikita, Masashi Mukohda, Sho Nakamura, Mihiro Seki, Ryuya Imai, Fumiyo Saito, Risuke Mizuno, Hiroshi Ozaki

{"title":"Enhanced vascular contraction induced by exposure to angiotensin II mediated by endothelin-1 biosynthesis following PKCβ activation.","authors":"Hirotaka Tajima, Nayu Morikita, Masashi Mukohda, Sho Nakamura, Mihiro Seki, Ryuya Imai, Fumiyo Saito, Risuke Mizuno, Hiroshi Ozaki","doi":"10.1152/ajpheart.00541.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00541.2024","url":null,"abstract":"Protein kinase C (PKC) reportedly plays a role in the pathogenesis of many vascular dysfunction-related conditions. In this study, we investigated whether PKCβ is associated with vascular contractile changes induced by angiotensin II (Ang II) exposure. Long-term (24 h) treatment of rat aortae and mesenteric arteries in Ang II-containing culture medium enhanced 5-hydroxytrypatamine (5-HT)-induced vascular contraction in a dose-dependent manner, in association with enhanced phosphorylation of PKCβ S660. Increased contraction induced by Ang II treatment was also observed in endothelium-denuded aorta. Enhanced contraction induced by Ang II was markedly diminished by knockout of the PKCβ gene or treatment with LY333531 and CGP53353 (PKCβ inhibitors). Cycloheximide (protein synthesis inhibitor) blocked the Ang II-induced enhanced contraction. Gene expression profiling and real-time PCR analyses showed marked upregulation of endothelin-1 (ET-1) expression in Ang II-treated aorta, but was not observed in PKCβ-knockout aorta. Ang II increased the secretion of ET-1 peptide in endothelium-intact and -denuded aortae. Ang II-induced enhancement of vascular contraction was diminished by BQ-123 (ETAR blocker). In vivo treatment with Ang II (250 ng/kg/min) for 7 days increased phosphorylation of PKCβ S660 in rat vascular tissue and increased the in vitro contractile responses to 5-HT and in vivo systolic blood pressure, but these changes were largely absent in PKCβ-knockout experiments. These data suggest that long-term exposure to Ang II increases vascular smooth muscle contraction and blood pressure elevation, mediated by activation of PKCβ and subsequent biosynthesis of ET-1 in vascular smooth muscle cells.","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063095","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}

引用次数: 0

Exposure to prenatal hypoxia impairs the function and structure of the carotid arteries in the adult offspring.

IF 4.1 2区医学

American journal of physiology. Heart and circulatory physiology Pub Date : 2025-01-31 DOI: 10.1152/ajpheart.00859.2024

Murilo E Graton, Amanda A de Oliveira, Aryan Neupane, Anita Quon, Raven Kirschenman, Floor Spaans, Sandra T Davidge

{"title":"Exposure to prenatal hypoxia impairs the function and structure of the carotid arteries in the adult offspring.","authors":"Murilo E Graton, Amanda A de Oliveira, Aryan Neupane, Anita Quon, Raven Kirschenman, Floor Spaans, Sandra T Davidge","doi":"10.1152/ajpheart.00859.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00859.2024","url":null,"abstract":"Prenatal hypoxia, a common pregnancy complication, can lead to vascular dysfunction, thereby increasing the risk of cardiovascular disease in the adult offspring. Carotid arteries are responsible for the majority of the blood flow to the brain/head, and carotid artery dysfunction is associated with life-threating cardiovascular events, such as stroke. However, whether prenatal hypoxia exposure impacts the function of the carotid arteries in the adult offspring is not known. We hypothesize that prenatal hypoxia impairs carotid artery function in the adult male and female offspring. Sprague Dawley rats were exposed to normoxia (21% O2) or hypoxia (11% O2) from gestational day (GD) 15 to 21 (term=22 days; n=9-11/group). Carotid arteries were isolated from the 4-month-old adult male and female offspring. Vasoconstrictor and vasodilatory properties were assessed by wire myography, and biomechanical properties (myogenic tone, circumferential stress and strain) by pressure myography. Collagen deposition (Masson's trichrome stain) and elastin density (Verhoeff stain) were measured in carotid artery cryosections. Prenatal hypoxia did not impact vasoconstriction or vasorelaxation responses in carotid arteries from both offspring. However, in males, prenatal hypoxia reduced carotid artery myogenic tone development and increased circumferential strain, which coincided with a lower collagen deposition and higher elastin density. In females, prenatal hypoxia tended to lower carotid artery circumferential strain (i.e., increased stiffness), without differences in myogenic tone or collagen/elastin density. Altogether, these data show that prenatal hypoxia exposure affects the carotid arteries of the adult offspring in a sex-specific manner, which may impact the blood flow regulation to the brain.","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063097","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}

引用次数: 0

In Vivo Effects of Cardiomyocyte-Specific Beta-1 Blockade on Afterload- and Frequency-dependent Cardiac Performance.

IF 4.1 2区医学

American journal of physiology. Heart and circulatory physiology Pub Date : 2025-01-31 DOI: 10.1152/ajpheart.00795.2024

Genri Numata, Yu Otsu, Shun Nakamura, Masayuki Toyoda, Hiroyuki Tokiwa, Yusuke Adachi, Taro Kariya, Kota Sueo, Mayo Shigeta, Takaya Abe, Tetsuo Sasano, Atsuhiko Naito, Issei Komuro, Eiki Takimoto

{"title":"In Vivo Effects of Cardiomyocyte-Specific Beta-1 Blockade on Afterload- and Frequency-dependent Cardiac Performance.","authors":"Genri Numata, Yu Otsu, Shun Nakamura, Masayuki Toyoda, Hiroyuki Tokiwa, Yusuke Adachi, Taro Kariya, Kota Sueo, Mayo Shigeta, Takaya Abe, Tetsuo Sasano, Atsuhiko Naito, Issei Komuro, Eiki Takimoto","doi":"10.1152/ajpheart.00795.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00795.2024","url":null,"abstract":"Pharmacologic beta-blockade is a well-established therapy for reducing adverse effects from sympathetic overactivity in cardiovascular diseases, such as heart failure. Despite decades of research efforts, in vivo cardiac functional studies utilizing genetic animal models remain scant. We generated a mouse model of cardiomyocyte-specific deletion of beta-1 adrenergic receptor (ADRB1) , the primary subtype expressed in cardiac myocytes, and demonstrated the role for ADRB1 in the maintenance of cardiac function at baseline and during exposure to increase in cardiac afterload by transient aortic occlusion and increasing heart rates (HRs) via atrial pacing. cKO hearts showed mildly depressed baseline left ventricular (LV) function, including slower HR, decreased contractility (dP/dtmax/IP) and prolonged relaxation (Tau) at baseline in both sexes. Exposure to increased LV afterload depressed LV function in either genotype similarly; however, the functional recovery following the removal of the afterload was severely impaired in cKO hearts, while cardiac function was immediately normalized in WT hearts. When HR was altered from 400 to 700bpm, cKO hearts were deficient in HR-dependent improvement of cardiac contractility and relaxation, known as positive force frequency relationship, that was evident in WT hearts. Enhanced phosphorylation of phospholamban by the HR increase was markedly blunted in cKO myocardium vs wild types, while CaMKII phosphorylation was comparable between the genotypes, suggesting the critical involvement of PKA. These results provide the first experimental evidence for the role of ADRB1 in cardiomyocytes for maintaining cardiac function at baseline and during acute stress, providing clinical perspective relating to the management of patients on beta-blockers.","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063106","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}

引用次数: 0

P2 purinergic receptors at the heart of pathological left ventricular remodeling following acute myocardial infarction.

IF 4.1 2区医学

American journal of physiology. Heart and circulatory physiology Pub Date : 2025-01-30 DOI: 10.1152/ajpheart.00599.2024

Ana Valéria Vinhais da Silva, Simon Chesseron, Oumnia Benouna, Jérôme Rollin, Sébastien Roger, Thierry Bourguignon, Stéphanie Chadet, Fabrice Ivanes

{"title":"P2 purinergic receptors at the heart of pathological left ventricular remodeling following acute myocardial infarction.","authors":"Ana Valéria Vinhais da Silva, Simon Chesseron, Oumnia Benouna, Jérôme Rollin, Sébastien Roger, Thierry Bourguignon, Stéphanie Chadet, Fabrice Ivanes","doi":"10.1152/ajpheart.00599.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00599.2024","url":null,"abstract":"Pathological left ventricular remodeling is a complex process following an acute myocardial infarction, leading to architectural disorganization of the cardiac tissue. This phenomenon is characterized by sterile inflammation and the exaggerated development of fibrotic tissue, which is non-contractile and poorly conductive, responsible for organ dysfunction and heart failure. At present, specific therapies are lacking for both prevention and treatment of this condition, and no biomarkers are currently validated to identify at-risk patients. Physiopathological understanding of this process is limited, probably due to the combination of the multi-cellular responses involved that are initially necessary for tissue healing but may be detrimental on longer term. Current research focuses on understanding and modulating the inflammatory response, a key aspect of the tissue healing process. Inflammation is triggered by the release of inflammatory mediators from cardiomyocytes undergoing cell death in the context of ischemia-reperfusion injury. Among them, extracellular ATP is a strong mediator of inflammation through the activation of P2 purinergic receptors, regulating the behavior of all the cellular actors of the post-myocardial infarction response and impacting organ function and recovery. Rather than considering each cellular protagonist independently, this review provides an integrated overview of the inflammatory and tissue response to myocardial infarction by members of the P2 receptor family. Finally, it explores the possibility of reducing pathological left ventricular remodeling through the modulation of these receptors and their associated signaling pathways.","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063110","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}

引用次数: 0

Unveiling Hidden Dangers: Quantitative Analysis of Ischemic Risks in High-Risk Patients with ASCVD and Dyslipidemia.

IF 4.1 2区医学

American journal of physiology. Heart and circulatory physiology Pub Date : 2025-01-29 DOI: 10.1152/ajpheart.00555.2024

Shih-Hsien Sung, Min-Ji Charng

{"title":"Unveiling Hidden Dangers: Quantitative Analysis of Ischemic Risks in High-Risk Patients with ASCVD and Dyslipidemia.","authors":"Shih-Hsien Sung, Min-Ji Charng","doi":"10.1152/ajpheart.00555.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00555.2024","url":null,"abstract":"Cardiovascular disease is one of the foremost causes of morbidity and mortality worldwide, with low-density lipoprotein cholesterol (LDL-C) identified as a significant risk factor for subsequent ischemic events. Elevated LDL-C contributes to vascular injury and fibrosis by upregulating the expression of connective tissue growth factor and collagen IV, which leads to endothelial cell dysfunction that initiates the process of atherosclerotic diseases. Currently, there is an absence of clear, risk-defined criteria to identify patients who are in greater needs for intensive LDL-C reduction, particularly with PCSK9 inhibitors. The data of ischemic risk associated with different patient types are scattered across the sub-analyses of FOURIER and ODYSSEY OUTCOMES trials, as well as trials that analyzed the plaque morphology of high-risk patients. It would be helpful to highlight the use of clinical features and plaque morphology and identify the patient types at higher ischemic risk. This article aims to provide a clear visualization of the ischemic risk associated with various types of patients with atherosclerotic cardiovascular disease (ASCVD) and dyslipidemia, and its implications to improve risk stratification for patients with unveiling hidden dangers.","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063114","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}

引用次数: 0

Clinical applications for lipid mediators in STEMI.

IF 4.1 2区医学

American journal of physiology. Heart and circulatory physiology Pub Date : 2025-01-29 DOI: 10.1152/ajpheart.00013.2025

Hiroe Toba, Denan Jin, Shinji Takai

引用次数: 0

Comprehensive Echocardiographic Protocol for Pigs with Emphasis on Diastolic Function: Advantages over MRI Assessment.

IF 4.1 2区医学

American journal of physiology. Heart and circulatory physiology Pub Date : 2025-01-28 DOI: 10.1152/ajpheart.00858.2024

Nadia Martinez Naya, Thomas E Sharp, Manuela G Sgai, Jose Mc Capcha, Lina A Shehadeh

{"title":"Comprehensive Echocardiographic Protocol for Pigs with Emphasis on Diastolic Function: Advantages over MRI Assessment.","authors":"Nadia Martinez Naya, Thomas E Sharp, Manuela G Sgai, Jose Mc Capcha, Lina A Shehadeh","doi":"10.1152/ajpheart.00858.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00858.2024","url":null,"abstract":"Swine are increasingly utilized in cardiovascular research due to their anatomical and physiological similarities to humans, particularly for studying diastolic dysfunction. While MRI offers excellent structural imaging, echocardiography provides superior real-time assessment of diastolic parameters. To address the lack of standardized methods and reduce variability across studies, we present a comprehensive guide for performing echocardiography in Yorkshire pigs, detailing anatomical considerations, equipment requirements, and technical approaches. We describe systematic approaches for obtaining and optimizing right parasternal long and short-axis views, apical four-chamber, and subcostal imaging windows, with specific attention to anatomical variations from human cardiac orientation and standard clinical transducer positioning. These tomographic views enable comprehensive assessment of systolic and diastolic function, including ventricular volumes, wall thicknesses, chamber dimensions, ejection fraction, and Doppler measurements of blood flow and tissue velocities. This standardized methodology for echocardiographic images acquisition enhances data reliability in cardiovascular pig models, improving the interpretation of preclinical study results and strengthening translational research outcomes. The protocol also provides consistency for veterinary applications, making echocardiography a preferred modality for longitudinal studies in this valuable translational model.","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051290","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}

引用次数: 0

Sexual Dimorphism in the Downregulation of Extracellular Matrix Genes Contribute to Aortic Structural Stiffness in Female Mice.

IF 4.1 2区医学

American journal of physiology. Heart and circulatory physiology Pub Date : 2025-01-28 DOI: 10.1152/ajpheart.00432.2024

Anne N Kamau, Anil Sakamuri, Delphine O Okoye, Divya Sengottaian, Jennifer Cannon, Josefa Guerrero-Milan, Jennifer C Sullivan, Kristin S Miller, Yutao Liu, Benard O Ogola

{"title":"Sexual Dimorphism in the Downregulation of Extracellular Matrix Genes Contribute to Aortic Structural Stiffness in Female Mice.","authors":"Anne N Kamau, Anil Sakamuri, Delphine O Okoye, Divya Sengottaian, Jennifer Cannon, Josefa Guerrero-Milan, Jennifer C Sullivan, Kristin S Miller, Yutao Liu, Benard O Ogola","doi":"10.1152/ajpheart.00432.2024","DOIUrl":"10.1152/ajpheart.00432.2024","url":null,"abstract":"The contribution of sex hormones to cardiovascular disease, including arterial stiffness, is established; however, the role of sex chromosome interaction with sex hormones, particularly in women, is lagging. Arterial structural stiffness depends on the intrinsic properties and transmural wall geometry that comprise a network of cells and extracellular matrix (ECM) proteins expressed in a sex-dependent manner. In this study, we used four-core genotype (FCG) mice to determine the relative contribution of sex hormones versus sex chromosomes or their interaction with arterial structural stiffness. Gonadal intact FCG mice included females (F) and males (M) with either XX or XY sex chromosomes (n=9-11/group). We isolated the thoracic aorta, and a tissue puller was used to assess structural resistance to changes in shape under control, collagenase, or elastase conditions. We determined histological collagen area fraction and evaluated aortic ECM genes by PCR microarrays followed by RT-qPCR. Stress-strain curves showed higher elastic modulus (P<0.001), denoting decreased extensibility in XXF compared to XYF aortas, which were significantly reversed by collagenase and elastase treatments (P<0.01). Aortic gene expression analysis indicated a significant reduction in Emilin1, Thbs2, and Icam1 in the XXF versus XYF aorta (P<0.05). Uniaxial stretching of XXF aortic vascular smooth muscle cells indicated decreased Thbs2, Ctnna1, and Ecm1 genes. We observed a significant (P<0.05) reduction in Masson's trichrome staining in collagenase but not elastase-treated aortic rings compared to the control. The increased aortic elastic modulus in XXF compared to XYF mice suggests a decrease in aortic extensibility mediated by a reduction in ECM genes.","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051365","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}

引用次数: 0

Sexual dimorphism in right ventricular adaptation to pressure overload involves differential angiogenic response.

IF 4.1 2区医学

American journal of physiology. Heart and circulatory physiology Pub Date : 2025-01-28 DOI: 10.1152/ajpheart.00549.2024

Erica R Seelemann, Sheethal Panchakshari, Parabhjot Kaur Labana, Maxwell M Wolverton, Yupu Deng, Haya AbdelWahab, Chris Consmueller, Duncan J Stewart, Ketul R Chaudhary

{"title":"Sexual dimorphism in right ventricular adaptation to pressure overload involves differential angiogenic response.","authors":"Erica R Seelemann, Sheethal Panchakshari, Parabhjot Kaur Labana, Maxwell M Wolverton, Yupu Deng, Haya AbdelWahab, Chris Consmueller, Duncan J Stewart, Ketul R Chaudhary","doi":"10.1152/ajpheart.00549.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00549.2024","url":null,"abstract":"This study investigated the sexual dimorphism in right ventricle (RV) remodeling in right heart failure susceptible Fischer CDF rats using the pulmonary artery banding (PAB) model. Echocardiography and hemodynamic measurements were performed in adult male and female Fischer CDF rats at 1- or 2-weeks post-PAB. RV systolic pressure and RV hypertrophy were significantly elevated in PAB rats compared to sham control at 1- and 2-weeks post-PAB; however, no differences were observed between male and female rats. Increase in cardiomyocyte cross-sectional area and RV end-diastolic diameter was observed in male rats compared to female rats at 2-weeks post-PAB. Conversely, higher fractional area change and cardiac index were observed in female rats compared to male rats at 2-weeks post-PAB. To explore the mechanisms, a focused PCR array was performed and higher expression of angiogenic genes, including sphingosine kinase-1 (Sphk1), was observed in the RV of female rats compared to male rats. Consistent with the higher angiogenic gene expression, female rats had a higher RV vascular density at 2-weeks post-PAB compared to male rats. Female RV endothelial cells (RVEC) had better angiogenic ability compared to male cells that was potentiated by estradiol. Furthermore, effect of estradiol on RVEC was inhibited by Sphk1 inhibitor (PF-543). Together, female Fischer CDF rats develop adaptive RV remodeling post-PAB compared to mal-adaptive remodeling in male rats. Moreover, the adaptive remodeling in female rats is associated with better RV angiogenic response that may result from better angiogenic ability of female RVEC and proangiogenic effects of estradiol through Sphk1.","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051364","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}

引用次数: 0

Hypertrophic heart failure promotes gut dysbiosis and gut leakage in interleukin 10-deficient mice.

IF 4.1 2区医学

American journal of physiology. Heart and circulatory physiology Pub Date : 2025-01-24 DOI: 10.1152/ajpheart.00323.2024

Prabhat Ranjan, Sumanta Kumar Goswami, Roshan Kumar Dutta, Karen Colin, Harish Chandra Pal, Qinkun Zhang, Hind Lal, Ram Prasad, Suresh Kumar Verma

{"title":"Hypertrophic heart failure promotes gut dysbiosis and gut leakage in interleukin 10-deficient mice.","authors":"Prabhat Ranjan, Sumanta Kumar Goswami, Roshan Kumar Dutta, Karen Colin, Harish Chandra Pal, Qinkun Zhang, Hind Lal, Ram Prasad, Suresh Kumar Verma","doi":"10.1152/ajpheart.00323.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00323.2024","url":null,"abstract":"Heart failure (HF) is a leading cause of death worldwide. We have shown that pressure overload (PO)-induced inflammatory cell recruitment leads to heart failure in IL-10 knockout (KO) mice. However, it's unclear if PO-induced inflammatory cells also target the gut mucosa, causing gut dysbiosis and leakage. We hypothesized that TAC (transverse aortic constriction) exacerbates immune cell homing to the gut (small intestine and colon), promoting dysbiosis and gut leakage in IL-10 KO mice. HF was induced in 8-10 weeks old C57BL/6J wild-type (WT) and B6.129P2-Il10tm1Cgn/J mutant (IL-10 KO) male and female mice by TAC and cardiac function was measured using visual sonics VEVO 3100. Fourteen days post-TAC, levels of monocytes, macrophages, neutrophils, and proinflammatory cytokines were measured in blood and gut. Gut dysbiosis was assessed via 16S rRNA sequencing in feces at 56 days post-TAC. IL-10 KO mice showed worsened cardiac dysfunction post-TAC. TAC worsened monocytes, and neutrophils infiltration in systemic circulation and facilitated their homing to the gut in IL-10 KO mice. Intriguingly, proinflammatory cytokines level was increased in blood, and gut of IL-10 KO mice following TAC. Furthermore, IL-10 expression was reduced in the colon of WT mice post-TAC. Moreover, TAC exacerbated gut dysbiosis in IL-10 KO mice. Finally, an impaired intestinal permeability was noted in IL-10 KO mice post-TAC. In conclusion, TAC-induced systemic inflammation leads to gut dysbiosis and impaired gut permeability in IL-10 KO mice, indicating IL-10's potential role in regulating intestinal integrity and microbiota balance during heart failure.","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031840","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}

引用次数: 0