Exercise-induced cellular changes promote improved function in ischemic hearts
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ABSTRACT:
PROVIDER: PRJNA1160835 | ENA |
REPOSITORIES: ENA
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Project description:Ischemic heart disease (IHD) remains a leading cause of mortality worldwide, often culminating in myocardial infarction (MI) and subsequent heart failure due to adverse fibrotic remodeling of the myocardium. Despite the lack of effective treatments, exercise has emerged as a promising strategy to reduce mortality risk and improve cardiac function post-MI. This study investigates the molecular mechanisms underlying exercise-induced cardioprotection by analyzing changes in several key cardiac cell populations after MI in a murine model. We assessed the effect of exercise preconditioning in mouse MI model through echocardiography, followed by single nuclei RNA-seq of cardiac cells, and validation by microscopy and flow cytometry. Our findings demonstrate that exercise significantly enhances cardiac function post-MI, as evidenced by improved ejection fraction and stroke volume in exercised mice. These improvements are linked to adaptive changes across multiple cardiac cell types. Notably, in infarcted mice, exercise caused a downregulation of cardiomyopathy-associated pathways, accompanied by changes in ECs, macrophages, fibroblasts and cardiomyocytes. Exercise stimulated formation of new capillaries which post-MI resulted in a more vascularized infarct border zone. Additionally, exercised hearts displayed a shift in macrophage populations towards a pro-regenerative phenotype, marked by an increase in resident CCR2- macrophages and a reduction in pro-inflammatory M1-gene expression. In cardiomyocytes, exercise enhanced pathways related to endothelial support and ATP biosynthesis, mitigating the upregulation of cardiomyopathy-associated pathways observed post-MI. Importantly, exercise also restored calcium signaling and reversed pathological potassium signaling, thereby preserving contractile function. Fibroblast analysis revealed that exercise stimulated activation of these cells to participate in scar formation. In conclusion, this study provides new insights into the cellular and molecular mechanisms through which exercise enhances cardiac function and provides cardio-protection post-MI, offering potential avenues for targeted therapies in patients with IHD.
2025-09-12 | GSE277123 | GEO
Project description:Pre-LVAD and explanted ischemic and nonischemic cardiomyopathy and nonfailing hearts all normalized with RMA Keywords: other
2004-10-26 | GSE1869 | GEO
Project description:Ischemic and non-ischemic cardiomyopathies have distinct etiologies and underlying disease mechanisms, which require in-depth investigation for improved therapeutic interventions. The goal of this study was to use clinically obtained myocardium from healthy and heart failure patients, and characterize the changes in extracellular matrix (ECM) in ischemic and non-ischemic failing hearts, with and without mechanical unloading. Using tissue engineering methodologies, we also investigated how diseased human ECM, in the absence of systemic factors, can influence cardiomyocyte function. Heart tissues from heart failure patients with ischemic and non-ischemic cardiomyopathy were compared to explore differential disease phenotypes and reverse remodeling potential of left ventricular assisted device (LVAD) support at transcriptomic, proteomic and structural levels. The collected data demonstrated that the differential ECM compositions recapitulated the disease microenvironment and induced cardiomyocytes to undergo disease-like functional alterations. In addition, our study also revealed molecular profiles of non-ischemic and ischemic heart failure patients and explored the underlying mechanisms of etiology-specific impact on clinical outcome of LVAD support and tendency towards reverse remodeling.
2022-01-12 | MSV000088676 | MassIVE
Project description:Pre-LVAD and explanted ischemic and nonischemic cardiomyopathy and nonfailing hearts all normalized with RMA
2007-08-25 | E-GEOD-1869 | biostudies-arrayexpress
Project description:A goal of this study was to identify and investigate previously unrecognized components of the remodeling process in the progression to heart failure by comparing gene expression in ischemic, failing (F) to non-failing (NF) hearts. These results also were compared to the changes observed in a proteomic analysis of F and NF hearts. RNA extracted from the left ventricle was hybridized to Affymetrix arrays to identify gene expression differences in ischemic, end-stage failing versus non-failing hearts. biological replicate: LV_NF_001, LV_NF002, LV_NF004, LV_NF005 biological replicate: LV_F_003, LV_F005, LV_F009, LV_F006
2016-02-08 | E-GEOD-76701 | biostudies-arrayexpress
Project description:A goal of this study was to identify and investigate previously unrecognized components of the remodeling process in the progression to heart failure by comparing gene expression in ischemic, failing (F) to non-failing (NF) hearts. These results also were compared to the changes observed in a proteomic analysis of F and NF hearts.
2016-02-08 | GSE76701 | GEO
Project description:To undertake transcriptome-wide microarray analysis to develop a view of molecular adaptations that may underpin any benefit associated with the mild exercise regime of voluntary running Total RNA obtained from isolated whole hearts subjected to 7 days of voluntary exercise compared to sedentary control hearts (n=6/group).
2011-11-01 | E-GEOD-32391 | biostudies-arrayexpress
Project description:In this study, we provide evidence that ischemic exercise, conducted as blood flow-restricted resistance exercise, promote changes in the micro-RNA cargo of circulating extracellular vesicles in healthy volunteers.
2020-04-12 | GSE136997 | GEO
Project description:Similar to remote ischemic preconditioning bouts of exercise may possess immediate protective effects against ischemia-reperfusion injury. However, underlying mechanisms are largely unknown. This study compared the impact of single and repeated handgrip exercise versus remote ischemic preconditioning on inflammatory biomarkers in patients with cerebral small vessel disease (cSVD). In this crossover study, 14 patients with cSVD were included. All participants performed 4-days of handgrip exercise (4x5-minutes at 30% of maximal handgrip strength) and remote ischemic preconditioning (rIPC; 4x5-minutes cuff occlusion around the upper arm) twice daily. Patients were randomized to start with either handgrip exercise or rIPC and the two interventions were separated by >9 days. Venous blood was drawn before and after one intervention, and after 4-days of repeated exposure. We performed a targeted proteomics on inflammation markers in all blood samples.
2023-03-11 | PXD037267 | Pride
Project description:Coronary heart disease is the leading cause of death worldwide. After an acute myocardial infarction, early reperfusion reduces infarct size, which correlates with improved clinical outcomes. Paradoxically, reperfusion although relieving ischemia, accelerates apoptosis in injured cardiomyocytes, which has led to the view that myocardial salvage is futile beyond the first few hours of reperfusion. In murine hearts subjected to 90 min of coronary artery occlusion and then 48 h of reperfusion, we show transient activation of intrinsic prosurvival insulin-like growth factor-1 (IGF-1) signaling. In these hearts, acute IGF-1 receptor inhibition decreases the abundance of prosurvival signaling molecules, and markedly activates caspase-3, a potent effector of apoptosis, in infarct border zone cardiomyocytes. We found that mouse mast cell protease-4 (MMCP-4) degraded IGF-1 in vitro by a novel catalytic activity of chymases. In vivo, this degradation, which is triggered by mast cell infiltration into the peri-infarct region and MMCP-4 extravasation, between 48 and 72 h post-ischemia/reperfusion (I/R), attenuates IGF-1 prosurvival signaling. In MMCP-4-deficient mice, while infarct size is not reduced at 24 h post-I/R, at 72 h post-I/R myocardial IGF-1 levels and signaling are increased, resulting in activation of the survival kinases Akt and ERK, inhibition of caspase-3, and reduced myocardial cell death. As a consequence, I/R-mediated loss of viable myocardium, adverse cardiac remodeling and contractile impairment are markedly reduced. Cardiomyocyte survival with consequent myocardial salvage may thus be possible even days after an ischemic insult, making them a novel therapeutic target for delayed cardioprotective therapy. Group 1 is wild type C57Bl6 uninjured hearts. These mice were not undergone any surgery and used as controls. Group 2 are wild type C57Bl6 72 h post-ischemia reperfusion (IR) injury hearts. These mice for subjected to ischemia reperfusion (IR) involving 90 min of left anterior descending coronary artery occlusion followed by reperfusion for 3 days or 72 h.
2015-09-01 | E-GEOD-61592 | biostudies-arrayexpress