Up-regulated MCPIP1 in abdominal aortic aneurysm is associated with vascular smooth muscle cell apoptosis and MMPs production

Abstract

Abdominal aortic aneurysm (AAA) is often clinically silent before rupture characterized by extensive vascular inflammation and degenerative elasticity of aortic wall. Monocyte chemotactic protein-induced protein-1 (MCPIP1) exhibits anti-infllammatory and pro-apoptotic effects involved in atherogenesis. However, little is known about the expression and the contribution of MCPIP1 in AAA. In the present study, we collected clinical AAA specimens and constructed AAA mice model through Ang-II infusion, and found apparently increased MCPIP1 expression and severe inflammatory infiltration in AAA aortic membrane as evidenced by elevated levels of monocyte chemotactic protein 1 (MCP-1), interleukin 1 β (IL-1β) and NF-κB, as well as HE staining. The elasticity of aortic tunica media was impaired along with multiple apoptosis of vascular smooth muscle cells (VSMCs) in Ang-II-induced aneurysmal mouse. In vitro Ang-II administration of VSMCs induced MCPIP1 expression, accompanied by up-regulation of matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9, as well as enhancement of VSMCs proliferation and apoptosis, which may cause damage of intima–media elasticity. Silencing MCPIP1 reversed above effects to further restore the balance of proliferation and apoptosis in VSMCs. Overall, our data indicated that up-regulation of MCPIP1 may become a promising candidate for the diagnosis of AAA, and specific knockdown of MCPIP1 in VSMCs could inhibit VSMCs apoptosis and down-regulate MMPs to maintain vascular wall elasticity. Therefore, knockdown of MCPIP1 may serve as a potential target for gene therapy of AAA.