Role of atherogenic lipoproteins in cytokine-mediated renovascular injury.

Recent advances have clarified many basic cellular and molecular mechanisms associated with glomerular injury. We propose that atherogenic lipoproteins (e.g., native LDL and its more atherogenic oxidized variants) play a central role as biological modifiers in monocyte- and cytoregulatory peptide-induced glomerulosclerosis. Following lipoprotein activation of mesangial and other intrinsic glomerular cells, monocytes adhere, transmigrate, differentiate, and proliferate within the glomerular mesangium. These events are mediated by increased expression of adhesion molecules (ICAM-1, VCAM-1, etc.) and specific monocyte chemoattractants (M-CSF, MCP-1, etc.). Furthermore, atherogenic lipoprotein can activate mesangial cells to express additional proinflammatory cytokines (TNF-alpha, TGF-beta, etc.) that culminate in the elaborated expression of extracellular matrix proteins and irreversible injury. These results support a distinct pathobiological role for atherogenic lipoproteins in the initiation and progression of cytokine-mediated renal injury.