Role of cytokines in cardiac fibrosis and exercise
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ABSTRACT:
PROVIDER: PRJNA529791 | ENA |
REPOSITORIES: ENA
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Project description:During acute sympathetic stress, the overeactivation of β-adrenergic receptors (β-ARs) caused cardiac fibrosis, by triggering inflammation and cytokine expression. It is unknown whether exercise training inhibited acute β-AR overactivation-induced cytokine expression and cardiac injury. Here, we reported that running exercise inhibited cardiac fibrosis and improved cardiac function in mice treated by isoproterenol, a β-AR agonist. Cytokine antibody array revealed that exercise prevented the expression changes of most cytokines induced by isoproterenol. Specifically, 18 ISO-upregulated and 3 ISO-downregulated cytokines belonged to six families (eg. chemokine) were prevented. A further KEGG analysis of these cytokines revealed that Hedgehog and Rap1 signaling pathways were involved in the regulation of cytokine expression by exercise. The expression changes of some cytokines that were prevented by exercise were verified by ELISA and real-time PCR. In conclusion, running exercise prevented the cytokine changes following acute β-AR overactivation and therefore attenuated cardiac fibrosis.
2019-03-30 | GSE129022 | GEO
Project description:Role of diet in cardiac aging and fibrosis
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Project description:The role of TMEM43 in cardiac fibrosis and dysfunction
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Project description:Physiological exercise leads to an activation of an distinct genetic program in the heart. During this process, we identified histone deacetlyase 4 (HDAC4) as an epigentic modifier, that regulates this adaptive process. To identify HDAC4 dependent genes that can are regulated after physiological stress, we investigated the cardiac gene expression in cardiomyocyte specific HDAC4 knockout animals and control animals after running exercise. We used microarrays to detail the global programme of gene expression underlying physiological cardiac adaption on exercise and identified distinct, histone deacetylase 4 dependent up-regulated genes during this process.
2017-06-07 | GSE72900 | GEO
Project description:Background: Postmenopausal women have higher risks of myocardial infarction (MI) and subsequent cardiac dysfunction. Exercise is widely recognized to protect the cardiovascular system, but its molecular mechanisms in postmenopausal MI remain not fully understood. This study explored the effects and mechanism of swimming exercise against cardiac dysfunction in ovariectomized (OVX) mice post-MI. Methods: OVX mice were subjected to a 3-week swimming training before MI induction via permanent ligation of left anterior descending artery. Cardiac systolic function was evaluated by echocardiography. Masson, HE, WGA staining, RT-qPCR, and Western blotting were combined to detect the extent of cardiomyocyte hypertrophy, myocardial fibrosis, and apoptosis. To explore the key exercise-effectors, we detected microRNAs (miR-21, miR-146a, miR-155) in serum samples of elderly post-MI women subsequent to exercise rehabilitation training. miR-21 expression was further investigated in heart sample of OVX plus MI mice. The role of miR-21 in vivo was elucidated through miR-21 knockout mice model and AAV9-mediated miR-21 overexpression mice model. The function of miR-21 in vitro were evaluated in cardiac fibroblasts isolated from OVX mice and treated with TGF-β to induce its activation. miR-21 targets were revealed by microarray analysis and verified by luciferase reporter and functional rescue assays. Results: Swimming significantly improved cardiac function in OVX mice post-MI, alleviated cardiomyocyte hypertrophy, reduced myocardial fibrosis, and inhibited apoptosis. miR-21 expression was downregulated by exercise training both in heart of OVX mice post-MI and in serum of elderly women after MI. miR-21 knockout mimicked swimming’s cardioprotective effects towards OVX mice post-MI, while miR-21 overexpression abolished these effects. The overexpression of miR-21 promoted the TGF-β-induced differentiation of cardiac fibroblasts into myofibroblasts and their proliferation, whereas its inhibition blocked TGF-β’s pro-fibrotic role. Microarray analysis and luciferase assays identified Sox7 as a direct miR-21 target, and Sox7 knockdown reversed anti-fibrotic effect of inhibiting miR-21. Conclusion: Swimming protects against post-MI cardiac dysfunction in OVX mice by downregulating myocardial miR-21, thereby upregulating its target gene Sox7 and inhibiting cardiac fibroblast activation. miR-21 and its downstream target Sox7 contributes to cardioprotective effects of swimming, offering a potential target for postmenopausal MI treatment.
2026-06-01 | GSE319401 | GEO
Project description:Background Pathological cardiac hypertrophy remains a major contributor to heart failure, with impaired glucose metabolism playing a central role. Although exercise is known to enhance myocardial glucose utilization, the long-term metabolic reprogramming effects of exercise and their role in preventing pathological hypertrophy are poorly understood. This study elucidates the mechanisms underlying the sustained metabolic memory induced by exercise hypertrophic preconditioning (EHP) and its cardioprotective effects, with a focus on RNA methylation and arachidonic acid metabolism. Methods We employed PET/CT to assess cardiac glucose uptake and bulk RNA sequencing to profile myocardial gene expression in sedentary (Sed) and EHP mice. Genetic manipulation of Pdk4 was achieved via adeno-associated virus mediated overexpression and tamoxifen-inducible, cardiac-specific knockout (Pdk4-CKO). Pressure overload was induced by transverse aortic constriction (TAC) in Pdk4-CKO and control (Myh6-CreER, MCM) mice. Epigenetic regulation of Pdk4 by EHP was investigated using pyrosequencing, SELECT-qPCR and dual-luciferase assays. Untargeted metabolomics and molecular docking, molecular dynamics simulation, and CETSA were performed on heart tissues and neonatal rat cardiomyocytes/fibroblasts to identify key metabolites and their mechanisms of action. Results: EHP conferred sustained myocardial glucose preference even after regression of physiological hypertrophy, mediated through METTL3-dependent m6A RNA methylation that suppressed Pdk4 expression. Pdk4 overexpression abolished EHP-mediated cardioprotection, whereas Pdk4 deletion enhanced cardiac function and attenuated fibrosis under pressure overload. Metabolomic profiling identified arachidonic acid-derived metabolites 5-KETE, 12-keto-leukotriene B4, and 20-hydroxy-leukotriene B4 as novel inhibitors of hypertrophy and fibrosis. These metabolites attenuated cardiomyocyte hypertrophy and fibroblast trans-differentiation through inhibition of the ERK2/MAPK1 pathway. Conclusions: This study establishes a unified mechanism by which EHP induces metabolic memory through RNA methylation-dependent suppression of Pdk4, leading to altered arachidonic acid metabolism and the accumulation of protective lipid mediators. These findings highlight the therapeutic potential of targeting the PDK4–arachidonic acid metabolites axis to mitigate pathological cardiac remodeling.
2026-04-18 | GSE315915 | GEO
Project description:Comparative analysis of mouse cardiac left ventricle gene expression: voluntary wheel exercise and pregnancy-induced cardiac hypertrophy We performed microarray analysis on RNA from left ventricles of mice in non-pregnant diestrus cycle, mid-pregnancy (MP), late-pregnancy (LP), and immediate post-partum (0PP). These were compared to 7days (7EX) and 21 days (21EX) of voluntary wheel running exercise.
2012-03-08 | E-GEOD-36330 | biostudies-arrayexpress
Project description:Cardiac fibrosis is a common pathological feature of various cardiac diseases that contributes significantly to heart failure progression and poor clinical outcomes. Recent genetic studies have shown that lower expression of CUB domain-containing protein 1 (CDCP1) is linked to myocardial recovery, but its direct role in cardiac pathophysiology remains unkown. In this study, we investigated the functional contribution of CDCP1 to pressure overload-induced cardiac remodeling and fibrosis. CDCP1 deletion attenuated Ang II/PE-induced cardiac dysfunction as demonstrated by reduced left ventricular mass index and improved cardiac function compared to wild-type controls. Histological analysis revealed significantly decreased cardiac fibrosis in CDCP1-KO mice. Transcriptomic profiling revealed that CDCP1 KO attenuates cardiac fibrosis through downregulation of matrix metalloproteases, collagen biosynthesis and limiting the pathological remodeling extracellular matrix. Spatial transcriptomics further revealed region-specific alterations in fibrotic and inflammatory signatures among the subtypes of cardiomyocytes and fibroblasts, suggesting localized CDCP1-dependent effects on cardiac remodeling. Our findings establish CDCP1 as a critical regulator of pressure overload-induced cardiac fibrosis and dysfunction. Our work provides direct evidence supporting CDCP1 inhibition as a potential therapeutic strategy for cardiac fibrosis.
2025-12-01 | GSE303631 | GEO
Project description:Comparative analysis of mouse cardiac left ventricle gene expression: voluntary wheel exercise and pregnancy-induced cardiac hypertrophy
2012-03-08 | GSE36330 | GEO