Published online Oct 26, 2024. doi: 10.4252/wjsc.v16.i10.873
Revised: August 21, 2024
Accepted: September 27, 2024
Published online: October 26, 2024
Processing time: 206 Days and 15.6 Hours
Myocardial ischemia-reperfusion injury (MIRI) poses a prevalent challenge in current reperfusion therapies, with an absence of efficacious interventions to address the underlying causes.
To investigate whether the extracellular vesicles (EVs) secreted by adipose mesenchymal stem cells (ADSCs) derived from subcutaneous inguinal adipose tissue (IAT) under γ-aminobutyric acid (GABA) induction (GABA-EVsIAT) demon
We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA. We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays. The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds. To explore the functional RNA diversity between EVsIAT and GABA-EVsIAT, we em
Our study demonstrates that, under the influence of GABA, ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs. Consequently, this leads to a more pronounced inhibitory effect on mitochondrial oxidative stress compared to EVs from ADSCs without GABA intervention, ultimately resulting in myocardial protection. On a molecular mechanism level, EVs regulate the expression of TXNIP and mitigating excessive oxidative stress in mitochondria during MIRI process to rescue cardiomyocytes.
Administration of GABA leads to the specific loading of miR-21-5p into EVs by ADSCs, thereby regulating the expression of TXNIP. The EVs derived from ADSCs treated with GABA effectively ameliorates mitochondrial oxidative stress and mitigates cardiomyocytes damage in the pathological process of MIRI.
Core Tip: Extracellular vesicles secreted by adipose mesenchymal stem cells derived from subcutaneous inguinal adipose tissue under γ-aminobutyric acid induction demonstrate a pronounced inhibitory effect on mitochondrial oxidative stress and showcases a safeguarding impact on the cardiomyocytes. The protective effects may result from extracellular vesicle microRNA-21-5p targeting thioredoxin (TXNIP)-interacting protein, regulating TXNIP-interacting protein-TXNIP complex formation and subsequent enhancing the antioxidant activity of TXNIP.