High-density lipoproteins protect endothelial cells from tumor necrosis factor-alpha-induced apoptosis

High-density lipoproteins (HDL) levels have been shown to be inversely corr elated with coronary heart disease, but the mechanisms of the direct protec tive effect of HDL on endothelial cells are not fully understood. The apopt osis of endothelial cells induced by cytokines and/or oxidized low-density lipoproteins, etc. may provide a mechanistic clue to the "response-to-injur y" hypothesis of atherogenesis. Here we report that HDL prevent the apoptos is of human umbilical venous endothelial cells (HUVECs) induced by tumor ne crosis factor-alpha (TNF-alpha) via an inhibition of CPP32-like protease ac tivity. The incubation of HUVECs with TNF-alpha significantly increased the CPP32-like protease activity, and induced apoptosis. Preincubation of HUVE Cs with HDL before incubation with TNF-alpha significantly suppressed the i ncrease in the CPP32-like protease activity, preventing apoptosis in a conc entration-dependent manner. These results suggest that HDL prevent the suic ide pathway leading to apoptosis of endothelial cells by decreasing the CPP 32-like protease activity and that HDL thus play a protective role against the "response-to-injury" hypothesis of atherogenesis, (C) 2000 Academic Pre ss.