Abstract

Homocysteine Affects Vascular Smooth Muscle Cell Proliferation by Interacting with Angiotensin II Type 1 and Type 2 Receptors Vascular smooth muscle cell (VSMC) proliferation is accepted to be important in the development of thickness of the arterial wall and causing myocardial infarction, abdominal aortic aneurysm, and atherosclerosis. Another risk factor is asserted 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 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. Cell proliferation was evaluated by MTT after 24 hours. After protein isolation, AGTR1 and AGTR2 protein expressions were determined by Western blotting. And AGTR1 and AGTR2 mRNA expressions were detected by RT-PCR. Hcy increased VSMC proliferation 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, 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.

Keywords: Angiotensin II type 1 receptor; Angiotensin II type 2 receptor; Homocysteine; Vascular smooth muscle cell; Cell culture