INTERACTIONS BETWEEN LIPOPROTEINS, GLOMERULAR CELLS AND MATRIX

Lipid deposition, mononuclear cell infiltration and accumulation of me sangial matrix components are recognized as early events in the develo pment of glomerulosclerosis whilst correction of plasma lipid abnormal ities slows the progression of renal disease in experimental models. I n vitro studies have demonstrated that low density lipoprotein (LDL) i s bound and internalized by mesangial cells, acts synergistically with growth factors to stimulate cellular proliferation and modifies secre tion of chemotactic mediators and matrix components. LDL incubated wit h mesangial cells becomes oxidized and in this modified from inhibits cell proliferation and causes cytotoxic injury. Oxidation of LDL also modulates its effects on cell secretory function. Since proteoglycans secreted by mesangial cells bind LDL particles, excess matrix accumula tion may exacerbate lipoprotein-mediated injury. These findings sugges t that lipoproteins deposited and oxidized in the glomerulus may promo te inflammation, cell injury and sclerosis.