Oxidized LDL, glomerular mesangial cells and collagen.

Lipid deposits, foam cell collection and accumulation of mesangial matrix components are recognized as early events in the development of focal segmental glomerulosclerosis (FSGS). Studies have suggested that oxidative stress is increased in uremic patients. Oxidized low-density lipoprotein (Ox-LDL) has been identified in the lesions of FSGS. Dietary antioxidants reduced not only the staining intensity of Ox-LDL but also the severity of renal injury in rats with experimental FSGS possibly by making lipoproteins resistant to oxidation. In vitro studies showed that LDL during its incubation with human mesangial cells (HMC) was peroxidatively modified and stimulated alpha1(I), alpha1(III), and alpha1(IV) collagen mRNA expression. Vitamin E, an antioxidant, and antibody against Ox-LDL caused a marked reduction in collagen mRNA stimulated by LDL. These findings suggest that LDL deposited and oxidized in the glomeruli may be implicated in the development of glomerulosclerosis by facilitating excessive mesangial matrix generation.