Oxidized low-density lipoprotein stimulates endothelin-1 release and mRNA expression from rat mesangial cells

Evidence indicates that the glomerular injuries and renal hemodynamic abnormalities in hyperlipidemia are caused by the interaction of low-density lipoprotein (LDL) and oxidized LDL (Ox-LDL) with mesangial cells. Experiments were designed to investigate whether the synthesis of mesangial cell endothelin-1 (ET-1), a potent renal vasoconstrictor and mitogen for mesangial cells, is modulated by LDL and Ox-LDL, Using competitive semi-quantitative reverse transcription polymerase chain reaction (PCR), we report that the expression of cultured rat mesangial cell ET-1 mRNA was increased after treatment with Ox-LDL but not native LDL. Ox-LDL stimulated the release of ET-1 peptide into the culture medium in a time- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 mu g/ml, and a higher dose of Ox-LDL was found to be cytotoxic to the mesangial cells. Our results suggest that ET-1 released by Ox-LDL stimulation may be an important pathogenetic factor contributing to the renal hemodynamic alterations and progressive chronic renal diseases induced by hypercholesterolemia.