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

Ming Xue,Dan Li,Zhu Wang,Gang Li,Jingjing Da,Lei Mi,Xing Jin

doi:10.1042/bsr20191252

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.

Highlights

Human abdominal aortic aneurysm (AAA) is a frequent age-related aortic disease with six-fold higher incidence among males over 60 years and females over 65 years [1,2]
We found the expression of monocyte chemotactic protein 1 (MCP-1), Monocyte chemotactic protein-induced protein-1 (MCPIP1) and IL1β were up-regulated in both AAA patients and Ang-II-induced aneurysmal mice suggesting an enhanced inflammation response
enzyme-linked immunosorbent assay (ELISA) analysis showed that serum levels of MCP-1, IL1β and NF-κB were significantly elevated in comparison with healthy control (Figure 1A–C, P

Summary

Introduction

Human abdominal aortic aneurysm (AAA) is a frequent age-related aortic disease with six-fold higher incidence among males over 60 years and females over 65 years [1,2]. Most AAA are asymptomatic until rupture, which is the leading cause of the high mortality of AAA. 80% AAA patients will die on the way to hospital and 50% of those undergo a ruptured surgery [3]. Open surgical or endovascular repair is the only clinical strategy for AAA, but is limited by the aortic diameter, as the surgery shows fewer benefits for small aneurysms typically

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Conclusion