Effect of angiotensin receptors on cell proliferation in homocysteine-treated rat vascular smooth muscle cells

Vascular smooth muscle cell (VSMC) proliferation is accepted to be important in the development of thickness of arterial wall and then causing miyocardial infrarction, abdominal aortic aneurysm and atherosclerosis. Another risk factor is asserted that to be the elevated plasma homocysteine (Hcy) level. It is thought that there is an interaction between these pathologies, which are caused by hyperhomocysteinemia (HHcy), and the renin angiotensin system (RAS), but the mechanism of this interaction is unknown. Therefore, the investigation of the relationship between Hcy and angiotensin II (Ang II) type 1 receptor (AGTR1) and type 2 receptor (AGTR2) be able to contribute to the explanation of the pathophysiology of cardiovascular diseases. For this purpose, Hcy, Hcy + AGTR1 antagonist (olmesartan), Hcy + AGTR2 agonist (CGP42112A) and Hcy + AGTR1 antagonist + AGTR2 agonist were treated to VSMC cultured from rat thoracic aorta and cell proliferation was evaluated by MTT after 24 hours. In these groups, after protein isolation, AGTR1 and AGTR2 protein expressions were determined by Western blotting, and level of treated AGTR1 and AGTR2 mRNA expressions were detected by RT-PCR. Hcy increased the proliferation of VSMC depending on the dose (p <0.01); AGTR1 antagonist and AGTR2 agonist reduced this proliferation (p <0.005).While Hcy increased the expression of AGTR1 protein and mRNA in VSMC, Hcy + AGTR1 antagonist treatment reduced protein and mRNA expression. However, whereas Hcy reduced AGTR2 protein and mRNA expression, Hcy + AGTR2 agonist treatment increased these expressions. As a result, Hcy can be increased VSMC proliferation through AGTR1 and AGTR2; this proliferation can be reduced by the treatment of the AGTR1 antagonist / AGTR2 agonist. Key words: Angiotensin II type 1 receptor, angiotensin II type 2 receptor, homocysteine, vascular smooth muscle cell.