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Research Paper

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

, , , , &
Pages 7872-7881 | Received 08 Jul 2021, Accepted 14 Aug 2021, Published online: 06 Oct 2021

Figures & data

Figure 1. REM preconditioning enhances the viability of HCMECs after H/R The viability of HCMECs pre-treated with different concentrations of REM, detected under normal conditions (a) and under H/R conditions (b), detected with CCK-8. *P < 0.05, ***P < 0.001 vs Control

Figure 1. REM preconditioning enhances the viability of HCMECs after H/R The viability of HCMECs pre-treated with different concentrations of REM, detected under normal conditions (a) and under H/R conditions (b), detected with CCK-8. *P < 0.05, ***P < 0.001 vs Control

Figure 2. REM preconditioning promotes the migration and angiogenesis of HCMECs after H/R The migration (a) and tube-like structure formation (b) abilities of HCMECs pre-treated with different concentrations of REM following H/R, detected by wound healing assay and Matrigel angiogenesis assay. ** P < 0.01, ***P < 0.001 vs Control

Figure 2. REM preconditioning promotes the migration and angiogenesis of HCMECs after H/R The migration (a) and tube-like structure formation (b) abilities of HCMECs pre-treated with different concentrations of REM following H/R, detected by wound healing assay and Matrigel angiogenesis assay. ** P < 0.01, ***P < 0.001 vs Control

Figure 3. REM preconditioning decreases the permeability of HCMECs after H/R and upregulates tight junction protein expression (a) The permeability of HCMECs pre-treated with different concentrations of REM following H/R, detected by in vitro vascular permeability kit. The intensity of fluorescence reflects the degree of cell permeability. (b-c) The expression of tight junction proteins in HCMECs pre-treated with different concentrations of REM following H/R, detected by western blot. *P < 0.05, ** P < 0.01, ***P < 0.001 vs Control

Figure 3. REM preconditioning decreases the permeability of HCMECs after H/R and upregulates tight junction protein expression (a) The permeability of HCMECs pre-treated with different concentrations of REM following H/R, detected by in vitro vascular permeability kit. The intensity of fluorescence reflects the degree of cell permeability. (b-c) The expression of tight junction proteins in HCMECs pre-treated with different concentrations of REM following H/R, detected by western blot. *P < 0.05, ** P < 0.01, ***P < 0.001 vs Control

Figure 4. REM preconditioning regulates the PI3K/Akt/HIF-1α signaling pathway in HCMECs The expression of relevant proteins to the PI3K/Akt/HIF-1α signaling pathway in HCMECs pre-treated with different concentrations of REM following H/R, detected by western blot. *P < 0.05, ** P < 0.01, ***P < 0.001 vs Control

Figure 4. REM preconditioning regulates the PI3K/Akt/HIF-1α signaling pathway in HCMECs The expression of relevant proteins to the PI3K/Akt/HIF-1α signaling pathway in HCMECs pre-treated with different concentrations of REM following H/R, detected by western blot. *P < 0.05, ** P < 0.01, ***P < 0.001 vs Control

Figure 5. PI3K/Akt inhibition rescues REM-promoted HCMEC viability, migration and angiogenesis after H/R The viability (a), migration (b) and tube-like structure formation (c) of HCMECs treated with REM following H/R in the presence of LY294002, correspondingly detected by CCK-8, wound healing and Matrigel angiogenesis assay. ***P < 0.001 vs Control; ##P < 0.01, ### P < 0.001 vs Model; @P < 0.05, @@@P < 0.001 vs H/R+ REM

Figure 5. PI3K/Akt inhibition rescues REM-promoted HCMEC viability, migration and angiogenesis after H/R The viability (a), migration (b) and tube-like structure formation (c) of HCMECs treated with REM following H/R in the presence of LY294002, correspondingly detected by CCK-8, wound healing and Matrigel angiogenesis assay. ***P < 0.001 vs Control; ##P < 0.01, ### P < 0.001 vs Model; @P < 0.05, @@@P < 0.001 vs H/R+ REM

Figure 6. PI3K/Akt inhibition reverses the protective effect of REM preconditioning on HCMEC endothelial barrier function after H/R (a) The permeability of HCMECs treated with REM following H/R in the presence of LY294002, detected by in vitro vascular permeability kit. The intensity of fluorescence reflects the degree of cell permeability. (b-c) The expression of tight junction proteins in HCMECs treated with REM following H/R in the presence of LY294002, detected by western blot. ***P < 0.001 vs Control; ### P < 0.001 vs Model; @P < 0.05, @@P < 0.01, @@@P < 0.001 vs H/R+ REM

Figure 6. PI3K/Akt inhibition reverses the protective effect of REM preconditioning on HCMEC endothelial barrier function after H/R (a) The permeability of HCMECs treated with REM following H/R in the presence of LY294002, detected by in vitro vascular permeability kit. The intensity of fluorescence reflects the degree of cell permeability. (b-c) The expression of tight junction proteins in HCMECs treated with REM following H/R in the presence of LY294002, detected by western blot. ***P < 0.001 vs Control; ### P < 0.001 vs Model; @P < 0.05, @@P < 0.01, @@@P < 0.001 vs H/R+ REM