Inhibitory effect of aliskiren on LPS-induced angiogenesis of HUVECs / 中国病理生理杂志

ABSTRACT

AIM:To investigate the inhibitory effect of aliskiren on the angiogenesis of human umbilical vein endothelial cells ( HUVECs) induced by lipopolysaccharide ( LPS) and to explore its possible mechanism.METHODS:HUVECs were cultured and randomly divided into blank group and renin group.The levels of tumor necrosis factor-α(TNF-α) and intercellular adhesion molecule-1 (ICAM-1) in the culture supernatant were detected by ELISA.The protein levels of Toll-like receptor 4 ( TLR4) and ICAM-1 in the HUVECs were determined by Western blot.HUVECs were cul-tured and randomly divided into control group, LPS group, low-dose (1μmol/L) aliskiren group, middle-dose (10μmol/L) aliskiren group and high-dose (100 μmol/L) aliskiren group.The proliferation of HUVECs was detected by MTT and BrdU assays.The mobility of HUVECs was measured by Transwell assay.The formation of the vessels was judged by ob-serving the formation of the luminal structure by HUVECs in Matrigel.The levels of TNF-α, ICAM-1 and monocyte chemo-tactic protein 1 ( MCP-1) in the culture supernatant were measured by ELISA.The expression of renin, TLR4, matrix me-talloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) at mRNA and protein levels in the HUVECs was determined by RT-PCR and Western blot.RESULTS:Renin stimulated the expression of inflammatory factors and TLR4 in the HUVECs.Aliskiren inhibited the growth, migration and angiogenesis of HUVECs in a dose-dependent manner, de-creased the levels of TNF-α, ICAM-1 and MCP-1 and the expression of renin, MMP-2 and MMP-9, and inhibited TLR4 expression (P<0.05).CONCLUSION:Aliskiren inhibits LPS-induced angiogenesis of HUVECs, which may be related to the down-regulation of renin expression, the inhibition of TLR4-mediated inflammatory reaction, and the formation of MMP-9 and MMP-2.