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Dexmedetomidine protects cardiac microvascular endothelial cells from the damage of ogd/r through regulation of the pparδ‐mediated autophagy
Author(s) -
Shao Qingbo,
Xia Jing,
Wu Pinwen,
Ying Jiazhou
Publication year - 2021
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12675
Subject(s) - autophagy , viability assay , apoptosis , reactive oxygen species , agonist , pharmacology , peroxisome proliferator activated receptor , microbiology and biotechnology , chemistry , biology , receptor , biochemistry
Background Dexmedetomidine (Dex) exerts an effective therapeutic role in numerous diseases associated with ischemia/reperfusion (I/R) injury via its anti‑apoptosis properties. Therefore, this study explores 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. Material and methods CMECs were pretreatment with different concentration of Dex, then exposed to OGD/R. Cell viability was measured with CCK‐8 assay. Apoptosis was evaluated by flow cytometry, and apoptosis‐related protein was determined by Western blot. Autophagy was assessed by transmission electron microscopy and autophagy‐related proteins. Besides, the role peroxisome proliferator‐activated receptors (PPARδ) in Dex‐mediated anti‐apoptosis property was validated with agonist and antagonist. Results OGD/R significantly decreased cell viability, increased reactive oxygen species, caused disorder of autophagy, and increased apoptosis in CMECs. Dex 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, expression level of Beclin1 and number of autophagosomes in the OGD/R‐induced CMECs. The mechanistic investigation indicated that PPARδ antagonist GW501516 aggravated cell damage following OGD/R, while PPARδ agonist GW6471 partly abolished the Dex‐mediated protective effects. Conclusions Dex activated the PPARδ‐AMPK‐PGC‐1α pathway‐mediated autophagy in CMECs, therefore to inhibit excessive apoptosis induced by OGD/R. Dex may potentially be a therapeutic intervention for myocardial I/R injury.