Objective—Alpha2-antiplasmin (2-AP) is the major circulating inhibitor of plasmin, which plays a determining role in the regulation of intravascular fibrinolysis. We investigated the role of ₂-AP on vascular remodeling in response to angiotensin II (Ang II).

Methods and Results—2-AP–deficient mice were performed. Ang II and N-nitro- L-arginine methyl ester (L-NAME)–induced perivascular fibrosis was significantly decreased in 2-AP^-/- mice compared with wild-type mice. In situ gelatinolytic activity analysis shows that perivascular gelatinolytic activity was increased in 2-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 I expression were significantly decreased in 2-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 2-AP^-/- mice.

Conclusion—The results show that 2-AP is a critical regulator for vascular remodeling by inhibiting p53/p21 pathway, suggesting that 2-AP is proposed to be a potential therapeutic target for vascular remodeling.