Angiotensin II-induced C-reactive protein generation: inflammatory role of vascular smooth muscle cells in atherosclerosis.
BACKGROUND
As the major target of Angiotensin II (Ang II) in the vessel wall, vascular smooth muscle cells (VSMCs) are a tentative source to produce C-reactive protein (CRP). However, it is largely unknown if Ang II is capable of inducing CRP production in VSMCs.


RESULTS
Ang II induced a concentration-dependent release of CRP in cultured rat VSMCs as measured by sandwich ELISA. Real-time PCR revealed that Ang II significantly upregulated CRP mRNA level in vitro. Ang II-induced CRP generation in aortic VSMCs was also investigated using double-labeled fluorescent immunohistochemistry and in situ hybridization in subchronic Ang II administration in rats. Losartan but not PD123319 markedly blocked the Ang II-induced CRP production in cultured VSMCs, suggesting that such effect was mediated via Ang II type 1 receptor. Further, Western blotting analysis showed that mitogen-activated protein kinase (MAPK) activation was obligatory in Ang II-induced CRP production, since specific MAPK inhibitor PD098059 almost abolished the action.


CONCLUSIONS
We identified that Ang II is capable of inducing CRP generation in VSMCs, in which Ang II type 1 receptor followed by MAPK signal pathway is involved. It strengthened the role of Ang II-induced CRP production by VSMCs in the inflammatory process in atherosclerosis.
Peng
Ning
N
Department of Pharmacology, Xi'an Jiaotong University School of Medicine and Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, PR China.
Liu
Jun-tian
JT
Gao
Deng-feng
DF
Lin
Rong
R
Li
Rui
R
D000804:Angiotensin II / Q000276:immunology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology*; D002097:C-Reactive Protein / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D019808:Losartan / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D020239:Receptor Cross-Talk
D047228:Angiotensin II Type 1 Receptor Blockers; D000804:Angiotensin II; D002097:C-Reactive Protein; D020928:Mitogen-Activated Protein Kinases; D019808:Losartan