Small Extracellular Microvesicles Mediated Pathological Communications Between Dysfunctional Adipocytes and Cardiomyocytes as a Novel Mechanism Exacerbating Ischemia/Reperfusion Injury in Diabetic Mice
Authors' conclusion
We demonstrate for the first time that miR-130b-3p enrichment in dysfunctional adipocyte-derived sEV, and its suppression of multiple antiapoptotic/cardioprotective molecules in cardiomyocytes, is a novel mechanism exacerbating MI/R injury in the diabetic heart.
Study context
- Population
- Adult male mice fed a normal or high-fat diet for 12 weeks; plasma small extracellular vesicles (sEV) from patients with T2DM
- Comparison
- Diabetic sEV vs nondiabetic conditions in MI/R injury
- Outcome
- MI/R injury
Main finding
As reported in the abstract
- Intramyocardial diabetic serum sEV in nondiabetic heart exacerbated MI/R injury (poorer cardiac function recovery, larger infarct size, greater cardiomyocyte apoptosis)
- Intramyocardial or systemic diabetic adipocyte sEV or high glucose/high lipid-challenged nondiabetic adipocyte sEV exacerbated MI/R injury
- Diabetic epididymal fat transplantation increased MI/R injury in nondiabetic mice; sEV biogenesis inhibitor mitigated MI/R injury in diabetic mice
- miR-130b-3p increased in diabetic serum sEV, diabetic adipocyte sEV and challenged nondiabetic adipocyte sEV
- Mature (not primary) miR-130b-3p increased in heart after diabetic sEV injection
- miR-130b-3p mimic exacerbated MI/R injury in nondiabetic mice; miR-130b-3p inhibitors attenuated it in diabetic mice
- AMPKα1/α2, Birc6 and Ucp3 are direct targets of miR-130b-3p; their overexpression (particularly AMPKα2) reversed its proapoptotic/cardiac harmful effect
- miR-130b-3p increased in plasma sEV from T2DM patients; their sEV exacerbated cardiomyocyte ischemic injury, blocked by miR-130b-3p inhibitor
Original publication
Small Extracellular Microvesicles Mediated Pathological Communications Between Dysfunctional Adipocytes and Cardiomyocytes as a Novel Mechanism Exacerbating Ischemia/Reperfusion Injury in Diabetic Mice. Circulation. Published 10 January 2020. doi:10.
Summarised from the published abstract; every number is checked against it