Effects of valsartan on angiotensin II-induced migration of human coronaryartery smooth muscle cells

The migration as well as proliferation of coronary artery medial smooth mus cle cells (SMC) into the intima is proposed to be an important process of i ntimal thickening in coronary atherosclerosis. In the current study, we exa mined the effects of the angiotensin type 1 receptor antagonist valsartan o n angiotensin II (Ang II)-induced migration of cultured human coronary arte ry SMC using Boyden's chamber methods. Ang II significantly stimulated huma n coronary artery SMC migration in a concentration-dependent manner between 10(-6) and 10(-8) mol/l when cells of passage 4 to 6 were used, However, t he migration response to Ang II was moderately decreased in cells of passag e 10 to 12, and was markedly decreased in cells of passage 15 to 17, compar ed to that of passage 4 to 6, Ang II-induced migration was blocked by the A ng II type 1 (AT(1)) receptor antagonist valsartan in a concentration depen dent manner. By contrast, the Ang II type 2 (AT(2)) receptor antagonist PD 123319 did not affect Ang II-induced migration. Ang II modestly increased t he cell number of human coronary artery SMC after a 24-h incubation. This i ncrease in cell numbers was also clearly blocked by valsartan, but not by P D 123319. These results indicate that Ang II stimulates migration as well a s proliferation via AT(1) receptors in human coronary artery SMC when cells of passage 4 to 6 are used, Valsartan may prevent the progression of coron ary atherosclerosis through an inhibition of Ang II-induced migration and p roliferation in these cells, although in vivo evidence is lacking.