Alpha2-Antiplasmin Is a Critical Regulator of Angiotensin II–Mediated Vascular Remodeling

Abstract

Objective— Alpha2-antiplasmin (α2-AP) is the major circulating inhibitor of plasmin, which plays a determining role in the regulation of intravascular fibrinolysis. We investigated the role of α 2 -AP on vascular remodeling in response to angiotensin II (Ang II). Methods and Results— α2-AP–deficient mice were performed. Ang II and N ω -nitro- L-arginine methyl ester (L-NAME)–induced perivascular fibrosis was significantly decreased in α2-AP −/− mice compared with wild-type mice. In situ gelatinolytic activity analysis shows that perivascular gelatinolytic activity was increased in α2-AP −/− mice, which was responsible for decreased perivascular fibrosis in response to Ang II and L-NAME. Ang II–induced arterial wall thickening, vascular cell proliferation, apoptosis, c-Myc, and collagen Ι expression were significantly decreased in α2-AP −/− mice compared with wild-type mice. Further analysis shows that increased p53 and p21 expression were responsible for inhibition of Ang II–induced vascular remodeling in α2-AP −/− mice. Conclusion— The results show that α2-AP is a critical regulator for vascular remodeling by inhibiting p53/p21 pathway, suggesting that α2-AP is proposed to be a potential therapeutic target for vascular remodeling.