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 microg/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.
Tan
M S
MS
Graduate Institute of Medicine, Kaohsiung Medical College, Taiwan, Republic of China.
Lee
Y J
YJ
Shin
S J
SJ
Tsai
J H
JH
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009994:Osmolar Concentration; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D019332:Endothelin-1; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein