Remifentanil pretreatment ameliorates H/R-induced cardiac microvascular endothelial cell dysfunction by regulating the PI3K/Akt/HIF-1α signaling pathway

Abstract

Restoration of blood supply through medical or surgical intervention is a commonly adopted method for acute myocardial ischemia, but is also a trigger for cardiac ischemia/reperfusion injury. Studies have shown that remifentanil (REM) displays cardioprotective effects. In this study, the effects of REM on HCMEC viability were examined before and after the induction of H/R using Cell Counting Kit-8 assays. Wound healing and Matrigel angiogenesis assays were performed to assess HCMEC migration and angiogenesis, respectively. Commercial kits and western blotting were used to determine the endothelial barrier function of H/R-stimulated HCMECs with or without REM treatment. The expression of PI3K/Akt/hypoxia-inducible factor-1α (HIF-1α) pathway-related proteins was detected by western blotting. After pre-treatment with PI3K/Akt, the effects of REM on H/R-induced HCMEC injury were examined. We found that pre-treatment with REM displayed no impact on HCMEC viability under normal conditions but noticeably improved cell viability following H/R. The migratory abilities and tube-like structure formations of H/R-stimulated HCMECs were both enhanced by REM in a concentration-dependent manner. REM also decreased the permeability of H/R-stimulated HCMECs and upregulated the expression of tight junction proteins. Furthermore REM increased the expression of PI3K/Akt/HIF-1α signaling-related proteins in HCMECs. Inhibition of PI3K/Akt rescued REM-enhanced HCMEC function under H/R condition. Therefore, the present study demonstrated that REM pretreatment ameliorated H/R-induced HCMEC dysfunction by regulating the PI3K/Akt/HIF-1α signaling pathway.

Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury

“…Furthermore, the HIF-1α/BNIP3-mediated regulation of mitophagy that we have discovered provides new insights into potential therapeutic targets for myocardial ischemia–reperfusion injury [ 69 ]. A growing body of scholars has begun to direct their attention towards the role of autophagy in myocardial protection, holding the promise of unveiling novel therapeutic strategies for MIRI [ 70 ]. A multitude of preclinical investigations have been undertaken to evaluate the pharmacological modulation of autophagic flux as a potent strategy against MIRI, yielding noteworthy outcomes.…”

Circ-Marc2 Silencing Protects Human Cardiomyocytes From Hypoxia/Reoxygenation–induced Injury by Modulating Mir-335-5p/Trpm7 Axis

“…In addition, the in vitro data should be validated using in vivo assay, which will be addressed in the following study according to the published method (30). H/R-driven cellular effects are also seen in other cardiomyocyte cell lines, such as H9C2 cells (31) and HL-1 cells (32), and cardiac microvascular endothelial cells (33). Thus, whether the circ-MARC2/miR-335-5p/TRPM7 pathway regulates H/R-driven cellular effects in other cardiomyocyte cell lines or cardiac microvascular endothelial cells will be analyzed in the future.…”

Delta Opioid Peptide Targets Brain Microvascular Endothelial Cells Reducing Apoptosis to Relieve Hypoxia-Ischemic/Reperfusion Injury

“…One of the opioids, fentanyl, showed improved ischemic wounds healing in the rat [ 43 ]. Remifentanil enhanced the expression of PI3K/Akt/HIF-1α signaling in H/R-induced cardiac microvascular endothelial cell to rescue its dysfunction [ 44 ]. These findings all could support the idea that opioids have potential benefits for endothelial cells against ischemic injury.…”