麻豆传媒

BACKGROUND

News — Myocardial ischemia-reperfusion injury (MIRI) poses a prevalent challenge in current reperfusion therapies, with an absence of efficacious interventions to address the underlying causes.

AIM

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-EVs^IAT) demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms.

METHODS

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 EVs^IAT and GABA-EVs^IAT, we employed microRNA (miR) sequencing. Through a dual-luciferase reporter assay, we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein (TXNIP). Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction.

RESULTS

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.

CONCLUSION

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.

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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.

• Citation: Wang FD, Ding Y, Zhou JH, Zhou E, Zhang TT, Fan YQ, He Q, Zhang ZQ, Mao CY, Zhang JF, Zhou J. Gamma-aminobutyric acid enhances miR-21-5p loading into adipose-derived stem cell extracellular vesicles to alleviate myocardial ischemia-reperfusion injury via TXNIP regulation. World J Stem Cells 2024; 16(10): 873-895
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