Endothelin-1 induces the expression of C-reactive protein in rat vascular smooth muscle cells.
Numerous studies have shown that both vasoconstrictive peptide endothelin-1 (ET-1) and inflammatory marker C-reactive protein (CRP) are implicated in the inflammatory process of atherosclerosis. The purpose of the present study was to observe effect of ET-1 on CRP production and the molecular mechanisms in rat vascular smooth muscle cells (VSMCs). The results showed that ET-1 was capable of stimulating VSMCs to produce CRP both in protein and in mRNA levels in vitro and in vivo. ET(A) receptor antagonist BQ123, but not ET(B) receptor antagonist BQ788, inhibited CRP production in VSMCs. In addition, ET-1 was able to elicit reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPK) activation, and antioxidant pyrrolidine dithiocarbamate and p38MAPK inhibitor SB203580 inhibited ET-1-induced CRP expression. The results demonstrate that ET-1 induces CPR production in VSMCs via ET(A) receptor followed by ROS and MAPK signal pathway, which may contribute to better understanding of the role of ET-1 in inflammatory activation of the vessel wall during atherogenesis.
Wang
Chenjing
C
Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, PR China.
Liu
Juntian
J
Guo
Fang
F
Ji
Yuanyuan
Y
Liu
Na
N
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D002097:C-Reactive Protein / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D017382:Reactive Oxygen Species; D044022:Receptor, Endothelin A; D002097:C-Reactive Protein; D048051:p38 Mitogen-Activated Protein Kinases; C072247:cyclo(Trp-Asp-Pro-Val-Leu)