Possible role of high density lipoprotein in the progression of glomerulosclerosis.

The collapsing variant of focal segmental glomerulosclerosis is a fulminant lesion characterized by rapid progression to end-stage renal disease. Substantial in vivo and in vitro evidence suggests that lipids, particularly low density lipoprotein (LDL), can contribute to the progression of glomerulosclerosis as they do in atherosclerosis. The nephrotic syndrome is typically associated with marked elevation of LDL and suppression of high density lipoprotein (HDL), abnormalities which may, accelerate both of these lesions.

Oxidation of extracellular matrix modulates susceptibility to degradation by the mesangial matrix metalloproteinase-2.

Protein oxidation occurs in aging and in various inflammatory conditions. Glomerulosclerosis is characterized by an accumulation of extracellular matrix (ECM) proteins and a paucity of glomerular mesangial cells and can be seen as an end-result of glomerular injury and in aging. ECM accumulation is the net result of the balance between synthesis and degradation.

Metal-catalyzed oxidation of extracellular matrix increases macrophage nitric oxide generation.

Background: Oxygen radicals are believed to play a significant role in glomerular disease. In part this may be due to oxidation of lipids, but protein oxidation may play a contributory role as well. We have demonstrated that the mesangial extracellular matrix is susceptible to metal-catalyzed oxidation and that this increases scavenger receptor-mediated adhesion of macrophages, cells which appear to be important participants in glomerular injury via their secretory products.

Metal-catalyzed oxidation of immunoglobulin G impairs Fc receptor-mediated binding to macrophages.

Enhanced oxidative stress is a feature of inflammatory and infectious conditions. Proteins may be important targets of oxidation and this may alter their function. We evaluated whether metal-catalyzed oxidation of IgG could alter its ability to bind to Fc receptors on macrophages.