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

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-1 alpha (HIF-1 alpha) 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-1 alpha 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-1 alpha signaling pathway.

Automated summary

The study demonstrated that pretreatment with remifentanil (REM) ameliorated H/R-induced human cardiac microvascular endothelial cell (HCMEC) dysfunction by regulating the PI3K/Akt/HIF-1 alpha signaling pathway. REM enhanced cell viability, migratory abilities, and tube-like structure formations of H/R-stimulated HCMECs in a concentration-dependent manner, while also decreasing cell permeability and upregulating tight junction proteins expression. Inhibition of PI3K/Akt rescued REM-enhanced HCMEC function under H/R condition.