Angiotensin II Induces Monocyte Chemoattractant Protein-1 Gene Expression in Rat Vascular Smooth Muscle Cells

• Published in: Circulation research 1998-11, Vol.83 (9), p.952-959
• Main Authors: Chen, Xi-Lin, Tummala, Pradyumna E, Olbrych, Matthew T, Alexander, R. Wayne, Medford, Russell M
• Format: Article
• Language: English
• Subjects: Angiotensin II - pharmacology; Angiotensin Receptor Antagonists; Animals; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Calcium-Calmodulin-Dependent Protein Kinases - physiology; Cardiology. Vascular system; Cells, Cultured; Chemokine CCL2 - genetics; Gene Expression Regulation - drug effects; Hydrogen Peroxide - pharmacology; Medical sciences; Multienzyme Complexes - antagonists & inhibitors; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; NADH, NADPH Oxidoreductases - antagonists & inhibitors; Nitric Oxide - physiology; Protein-Tyrosine Kinases - physiology; Rats; RNA, Messenger - analysis
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.83.9.952

Monocyte infiltration into the vessel wall, a key initial step in the process of atherosclerosis, is mediated in part by monocyte chemoattractant protein-1 (MCP-1). Hypertension, particularly in the presence of an activated renin-angiotensin system, is a major risk factor for the development of atherosclerosis. To investigate a potential molecular basis for a link between hypertension and atherosclerosis, we studied the effects of angiotensin II (Ang II) on MCP-1 gene expression in rat aortic smooth muscle cells. Rat smooth muscle cells treated with Ang II exhibited a dose-dependent increase in MCP-1 mRNA accumulation that was prevented by the AT (1) receptor antagonist losartan. Ang II also activated MCP-1 gene transcription. Inhibition of NADH/NADPH oxidase, which generates superoxide and H2 O2, with diphenylene iodonium or apocynin decreased Ang II-induced MCP-1 mRNA accumulation. Induction of MCP-1 gene expression by Ang II was inhibited by catalase, suggesting a second messenger role for H2 O2. The tyrosine kinase inhibitor genistein and the mitogen-activated protein kinase kinase inhibitor PD098059 inhibited Ang II-induced MCP-1 gene expression, consistent with a mitogen-activated protein kinase-dependent signaling mechanism. Ang II may thus promote atherogenesis by direct activation of MCP-1 gene expression in vascular smooth muscle cells. (Circ Res. 1998;83:952-959.)