Angiotensin II-mediated apoptosis on human vascular smooth muscle cells

Abstract

While previous studies demonstrated that angiotensin II is a potent vasoconstrictor and mitogenic factor, the effect of angiotensin II on apoptosis in vascular smooth muscle cells remain controversial. Therefore, the current study was designed to investigate the action of angiotensin II on apoptosis in human vascular smooth muscle cells. Human saphenous vein was obtained from coronary artery bypass surgery (n = 6) and was minced and incubated in the special tissue culture system in the absence or presence of angiotensin II (10⁻⁷ M) for 24 h. These studies were repeated with co-incubation of losartan (AT-1 receptor antagonist, 10⁻⁶ M) or PD-123319 (AT-2 receptor antagonist, 10⁻⁶ M). To detect the in situ DNA fragmentation, TUNEL staining was performed. TUNEL staining demonstrated that angiotensin II increased apoptosis in human vascular smooth muscle cells. This action of angiotensin II was enhanced by losartan and attenuated by PD-123319. Furthermore, co-incubation with both losartan and PD-123319 significantly reduced apoptosis levels. In conclusion, these data demonstrated that angiotensin II has potent apoptotic effect in human vascular smooth muscle cells through both AT-1 and AT-2 receptors. Furthermore, angiotensin II through AT-2 receptor has more potent apoptotic action in human vascular smooth muscle cells. This study indicated that angiotensin II plays an important role in the processes of apoptosis via angiotensin II receptors in human vascular smooth muscle cells.