Very low-density lipoprotein stimulates the expression of monocyte chemoattractant protein-1 in mesangial cells

Background Elevated plasma levels of very low-density lipoprotein (VLDL) ar e associated with an increased risk for focal glomerulosclerosis, which is analogous to atherosclerosis. One feature of focal glomerulosclerosis is th e presence ol foam cells derived from the infiltration of circulating monoc ytes. Mesangial cells are able to express monocyte chemoattractant protein- 1 (MCP-1). In this study, the ability of VLDL to stimulate MCP-1 expression in mesangial cells and consequent monocyte adhesion was investigated. Methods. For adhesion studies, mesangial cells isolated from Sprague-Dawley rats were treated with VLDL for six hours. followed by a one-hour incubati on with Tamm-Horsfall protein-1 (THP-1) cells. Mesangial MCP-1 mRNA levels were determined by reverse transcription-polymerase chain reaction. MCP-1 p rotein was determined by solid-phase immunoassay. Results. VLDL (100 to 300 mu g/mL) significantly enhanced the expression an d secretion of MCP-1 (54 to 285 ng/well) in mesangial cells. Such an effect was accompanied by the increased adhesion of monocytes to mesangial cells and later the formation of foam cells from monocytes after ingesting excess ive amounts of VLDL lipids. VLDL-induced MCP-1 expression and monocyte adhe sion were blocked by a protein kinase C inhibitor (staurosporine), as well as a calcium channel blocker (diltiazem). Conclusions. Our results demonstrate that elevated levels of VLDL. through the action of MCP-1, may contribute to the infiltration of monocytes into t he mesangium and subsequent foam cell formation. Hence. VLDLs may play a ro le in the pathogenesis of focal glomerulosclerosis. One of the mechanisms o f such effect may be mediated through the calcium-dependent protein kinase C pathway.