Effect of lycopene on oxidized low-density lipoprotein induced apoptosis of cerebral vascular endothelial cells by regulating the RAS homologous gene family member A/Rho-related kinase signaling pathway

Objective To investigate the effect of lycopene (LYC) on the oxidized low-density lipoprotein (ox-LDL) induced apoptosis of cerebral vascular endothelial cells (EC) by regulating the RAS homologous gene family member A (RhoA)/Rho-related kinase (ROCK) signaling pathway.

Methods Human brain microvascular endothelial cells (HBMECs) without any treatments were designed as NC group; the HBMECs treated with ox-LDL were divided into ox-LDL group, LYC group (HBMECs treated with 0.5 μmol/L LYC), lysophosphatidic acid (LPA) group (HBMECs treated with 5 μmol/L RhoA/ROCK signaling pathway activator LPA), and LYC+LPA group (HBMECs treated with 0.5 μmol/L LYC and 5 μmol/L LPA); after 24 hours of treatment, they were used for subsequent experiments. Enzyme-linked immunosorbent assay (ELISA) was used to detect the cytokine levels of HBMECs; CCK-8 method was used to detect the proliferation of HBMECs; flow cytometry was used to detect the apoptosis rate of HBMECs; the Western blot was used to detect the expression levels of platelet endothelial cell adhesion molecule-1 (CD31), smooth muscle (SM) 22α, BCL-2 associated X protein (Bax), B-cell lymphoma/leukemia 2 protein (Bcl-2), cleaved-Caspase-3, and RhoA/ROCK pathway related proteins.

Results Compared with the NC group, the levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), vascular endothelial cell adhesion molecule-1 (VCAM-1), apoptosis rate of HBMECs, the Bax, cleaved-Caspase-3, SM22α, RhoA and ROCK1 proteins in the ox-LDL group increased significantly, while the OD value and the levels of Bcl-2 and CD31 proteins decreased significantly (P < 0.05); compared with the ox-LDL group, the levels of MCP-1, IL-6, VCAM-1, apoptosis rate of HBMECs, the Bax, cleaved-Caspase-3, SM22α, RhoA, and ROCK1 proteins in the LYC group decreased significantly, while the OD value and the levels of Bcl-2 and CD31 proteins increased significantly (P < 0.05), but the trends in the LPA group were opposite; LPA weakened the improvement effect of LYC on apoptosis of HBMECs induced by ox-LDL.

Conclusion LYC may reduce apoptosis of HBMECs by inhibiting the RhoA/ROCK signaling pathway.