Involvement of profilin-1 in angiotensin II-induced vascular smooth muscle cell proliferation

Profilin-1, a regulator of actin polymerization, has recently been linked to vascular hypertrophy and remodeling. Whether profilin-1 is involved in angiotensin (Ang) II-induced proliferation of vascular smooth muscle cells leading to vascular remodeling in hypertension remains unclear. The present study was designed to analyze the correlation of profilin-1 and vascular remodeling during hypertension and to evaluate the role of profilin-1 in proliferation of vascular smooth muscle cells and the underlying mechanisms. The vascular morphology and the expression of profilin-1 in arterial tissues of spontaneously hypertensive rats and Wistar-Kyoto rats were assessed. The profilin-1 expression was significantly increased concomitantly with definite vascular remodeling by evaluating the media thickness, lumen diameter, media thickness-to-lumen diameter ratio and mean nuclear area in artery media in spontaneously hypertensive rats, which was inhibited by treatment with losartan. In cultured rat aortic smooth muscle cells (RASMCs), Ang II induced profilin-1 expression in a dose- and time-dependent manner. Knockdown of profilin-1 using small hairpin RNA inhibited Ang II-induced proliferation of RASMCs. Moreover, blockade of JAK2/STAT3 signaling pathway also inhibited Ang II-induced proliferation of RASMCs and profilin-1 expression. These results suggest that profilin-1 mediates the proliferation of RASMCs induced by Ang II via activation of Ang II type 1 receptor/JAK2/STAT3 signaling pathway, which may contribute to vascular remodeling in hypertension. (C) 2011 Elsevier Inc. All rights reserved.