ABSTRACT
Carbamylated LDL was shown to interact with cell surface receptors in human fi broblasts and to prevent the binding of native LDL in human fi broblasts (Weisgraber et al. 1978). LDL isolated from uremic patients as well as chemically carbamylated LDL had a slower clearance from plasma in rabbits than LDL from normal subjects or non-modifi ed LDL (Horkko et al. 1992, 1994). Our studies showed that cLDL activates MAPK pathway and induces injury and dysfunction of endothelial cells in vitro (Ok et al. 2005, Apostolov et al. 2007a). Th e cLDL eff ects were dose-dependent and relevant to atherosclerosis: irreversible cell injury and apoptosis in endothelial cells, and vascular smooth muscle cell (VSMC) proliferation (Ok et al. 2005). Th erefore, the cytotoxicity of cLDL is similar to the previously observed cytotoxicity of oxLDL (Galle et al. 1999) and acetylated LDL (Dart and Chin-Dusting 1999). Our recent data suggest that cLDL is capable of binding by and internalization to endothelial cells (Apostolov et al. 2008). Additionally, cLDL may transmigrate through endothelium. It utilizes a unique spectrum of scavenger receptors, in which lectin-like oxLDL receptor (LOX-1), CD36, SREC-1 and SR-A1 receptors are essential for the pro-atherogenic eff ects of cLDL on human endothelial cells. Th ese data are in agreement with other reports, which describe that scavenger receptors may upregulate both ICAM-1 and VCAM-1 expression in response to treatment
with other modifi ed LDLs (Chen et al. 2005, Inoue et al. 2005). Th erefore, it seems plausible that cLDL-induced monocyte adhesion is mediated through scavenger receptors and subsequent ICAM-1/VCAM-1 overexpression.
