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Small Extracellular Vesicles Secreted by Brown Adipose Tissue Mediate Exercise Cardioprotection via MicroRNA-Dependent Suppression of the MAPK Pathway

ABSTRACT: Long-term exercise provides reliable cardioprotection via incompletely understood mechanisms.The sEVs secreted by BAT participate in exercise cardioprotection via delivering the cardioprotective miRNAs into the heart. These results provide novel insights into the mechanisms underlying the BAT-cardiomyocyte interaction and highlight BAT sEVs and their contained miRNAs as alternative candidates for exercise cardioprotection.

ORGANISM(S): Mus musculus

PROVIDER: GSE196665 | GEO | 2022/02/15

REPOSITORIES: GEO

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Small Extracellular Vesicles Secreted by Brown Adipose Tissue Mediate Exercise Cardioprotection via MicroRNA-Dependent Suppression of the MAPK Pathway

Project description:Small Extracellular Vesicles Secreted by Brown Adipose Tissue Mediate Exercise Cardioprotection via MicroRNA-Dependent Suppression of the MAPK Pathway

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Knockdown of miR-192 and miR-432 in progenitor cell-derived small extracellular vesicles enhances tissue repair in myocardial infarction

Project description:Small extracellular vesicles (sEVs) play a critical role in cardiac cell therapy by delivering molecular cargo and mediating cellular signaling. Among sEV cargo molecule types, microRNA (miRNA) is particularly potent and highly heterogenous. However, not all miRNAs in sEV are beneficial. Two previous studies utilizing computational modeling identified miR-192-5p and miR-432-5p as potentially deleterious in cardiac function and repair. Here, we show that knocking down miR-192-5p and miR-432-5p in cardiac c-kit+ cell-derived sEVs enhances the therapeutic capabilities of sEVs in vitro and in a rat in vivo model of cardiac ischemia reperfusion. miR-192-5p and miR-432-5p depleted CPC-sEVs enhance cardiac function by reducing fibrosis, enhancing mesenchymal stromal cell-like cell mobilization, and inducing macrophage polarization to the M2 phenotype. Knocking down deleterious miRNAs from sEV could be a promising therapeutic strategy for treatment of chronic myocardial infarction.

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Differential expression of myocardial microRNAs is implicated in dexmedetomidine induced cardioprotection in rats

Project description:Using the highly sensitive miRNA array, we screened 83 microRNAs abundant in the myocardium and we explored the functions of these miRNAs by Gene Ontology and Kyoto Encyclopedia of Genes annotation. The enrichment results indicated that these miRNAs mainly participated in the phosphatidylinositol signaling system, PI3K-Akt, and MAPK. Furthermore, the TTC staining results showed that dexmedetomidine preconditioning attenuates myocardial ischemia-reperfusion injury by desregulation of several miRNAs and their potential target genes, which will give new insights into disclosing the mechanism of dexmedetomidine-induced cardioprotection.

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Exercise in adult zebrafish promotes ventricular cardiomyocyte proliferation in the regenerating heart

Project description:Exercise promotes a set of physiological adaptations known to provide long-term health benefits and it can play an important role in cardioprotection. However, the mechanisms underlying exercise-induced cardiac adaptation are not fully understood. In the present study, we examined cardiac adaptive responses to exercise training in the adult zebrafish and in the context of cardiac regeneration.We found that swimming-induced exercise increased cardiomyocyte proliferation and that this response was also found under regenerating conditions, when exercise was performed either prior to and after ventricular cryoinjury (CI). Exercise prior to CI resulted in a mild improvement in cardiac function and lesion recovery over the non-exercise condition.Transcriptomic profiling of regenerating ventricles in cryoinjured fish subjected to exercise revealed a differential regulation of genes related toregeneration as well as other biological processes potentially involved in the exercise response. Taken together, these results suggest that exercise constitutes a physiological stimulus thatmay help promote cardiomiogenic mechanisms of the vertebrate heart and that the zebrafish exercise model may be useful for evaluating the potential cardioprotective effects of exercise.

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Transcription profiling of rat heart left ventricle after exercise to investigate the role of exercise as a known protective factor against cardiovascular morbidity and mortality

Project description:Physical exercise training is a known protective factor against cardiovascular morbidity and mortality. Nevertheless, the underlying specific molecular mechanisms still remain uncompletely explored. To identify molecular mechanisms by which exercise training induces this favorable phenotype a genomic approach was used in an animal model of mild exercise previously demonstrated by our group to induce cardioprotection. Our data indicate that mild exercise by inducing no or few permanent changes in gene expression profile is able to determine cardioprotection without induction of cardiac hypertrophy. Experiment Overall Design: We investigated the gene expression profile by Affymetrix technology (230 2.0 GeneChip rat genome array) induced by mild exercise training (treadmill running: 25 m/min, 10% incline, 1 h/day, 3 days/week, 10 weeks) on left ventricle (LV) of exercise-trained (n=10) and sedentary control (n=10) rats.

2008-04-09 | E-GEOD-7640 | biostudies-arrayexpress

Gene expression profile induced by moderate physical exercise in heart left ventricles in rats

Project description:Physical exercise training is a known protective factor against cardiovascular morbidity and mortality. Nevertheless, the underlying specific molecular mechanisms still remain uncompletely explored. To identify molecular mechanisms by which exercise training induces this favorable phenotype a genomic approach was used in an animal model of mild exercise previously demonstrated by our group to induce cardioprotection. Our data indicate that mild exercise by inducing no or few permanent changes in gene expression profile is able to determine cardioprotection without induction of cardiac hypertrophy. Keywords: Case-Control: Response to physical exsercise

2008-07-15 | GSE7640 | GEO

Acute and chronic liver injury change the small RNA cargoes carried by serum small extracellular vesicles in mice

Project description:Compared to whole serum miRNAs, miRNAs in serum small extracellular vesicles (sEVs) are well protected form RNA enzymes, thus provide a consistent source of miRNA for disease biomarker detection. Serum sEVs and their miRNA cargos released by injured liver cells could be promising biomarkers for diagnosis of liver diseases. We were very interested to find out the effects of liver injury on serum extracellular vesicles as well as the small RNA components they transported, if there is any difference between acute and chronic injury. Study in this regard will help us to identify new serum biomarkers for liver injury, and to find out if there are specific markers for acute or chronic liver injury. To identify potential biomarker for liver injury based on serum sEVs miRNAs, we established the carbon tetrachloride (CCL4) induced acute and chronic liver injury mice model, and examined the dynamic changes of small RNA components, especially miRNAs, in serum sEVs.

2021-08-07 | E-MTAB-9462 | biostudies-arrayexpress

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