Dexmedetomidine protects cardiac microvascular endothelial cells from the damage of OGD/R through regulation of the PPAR δ‐mediated autophagy

This study explored the cardioprotective effects of Dex in cardiac microvascular endothelial cells (CMECs) in response to oxygen ‐glucose deprivation and re‐oxygenation (OGD/R) injury and its potential mechanism. CMECs was exposed to OGD/R with the pretreatment of different concentration of Dex, then. The results found that OGD/R significantly decreased cell viability, increased reactive oxygen species, caused disorder of autophagy and increased apoptotic rates in CMECs. However, Dex pretreatment enhanced the viability of the OGD/R‐treated CMECs, and effectively decreased reactive oxygen species production. Autophagy in CMECs was activated by Dex, as evidenced by the increase in the ratio of LC3B‐II/I, the expre ssion level of Beclin1 and the number of autophagosomes in OGD/R‐induced CMECs. These effects were further confirmed by autophagy inhibitor 3‐MA. The mechanistic investigation indicated that PPARδ agonist GW501516 further enhanced, whereas PPARδ antagonist GSK3787 partly abolished the Dex‐me diated protective effects in OGD/R‐induced CMECs. In sum, Dex activated the PPARδ‐AMPK‐PGC‐1α pathway‐mediated autophagy, therefore to inhibit OGD/R‐induced cell apoptosis in CMECs. Dex may potentially be a therapeutic intervention for myocardial I/R injury.
Source: Microcirculation - Category: Research Authors: Tags: ORIGINAL ARTICLE Source Type: research