Endothelin-1 decreases CD36 protein expression in vascular smooth muscle cells.
Recent studies have shown that CD36 plays important roles as a major scavenger receptor for oxidized low-density lipoproteins and as a crucial transporter for long-chain fatty acids. CD36 deficiency might be associated with insulin resistance and abnormal dynamics of long-chain fatty acids. Endothelin-1 (ET-1), which is synthesized and secreted by vascular endothelial cells, is the most potent endogenous vasoconstrictor known and also stimulates the proliferation of vascular smooth muscle cells (VSMCs) and thus is believed to play an important role in the development of various circulatory disorders, including hypertension and atherosclerosis. The aim of the present study was to investigate the regulatory effect of ET-1 on CD36 expression in cultured VSMCs. VSMCs were treated for different times (0-24 h) with a fixed concentration (100 nM) of ET-1 or with different concentrations (0-100 nM) for a fixed time (24 h); then CD36 expression was determined using Western blots. CD36 expression was significantly decreased by ET in a time- and dose-dependent manner. This inhibitory effect was prevented by the ET(A) receptor antagonist BQ-610 (10 microM) but not the ET(B) receptor antagonist BQ-788 (10 microM). To further explore the underlying mechanisms of ET-1 action, we examined the involvement of the tyrosine kinase-mediated and MAPK-mediated pathways. The inhibitory effect of ET-1 on CD36 protein expression was blocked by inhibition of tyrosine kinase activation by use of genistein (100 microM) and by the ERK inhibitor PD-98059 (75 microM) but not by the p38 MAPK inhibitor SB-203580 (20 microM). In conclusion, we have demonstrated that ET-1, acting via the ET(A) receptor, suppresses CD36 protein expression in VSMCs by activation of the tyrosine kinase and ERK pathways.
Kwok
Ching Fai
CF
Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Juan
Chi-Chang
CC
Ho
Low-Tone
LT
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018110:Receptors, Lipoprotein / Q000378:metabolism*
D018955:CD36 Antigens; C008132:Cd36 protein, rat; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D018110:Receptors, Lipoprotein; D011505:Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases