Abdominal Aortic Aneurysm Formation with a Focus on Vascular Smooth Muscle Cells

Abstract

Abdominal aortic aneurysm (AAA) is a lethal degenerative vascular disease that affects, mostly, the elder population, with a high mortality rate (>80%) upon rupture. It features a dilation of the aortic diameter to larger than 30 mm or more than 50%. Diverse pathological processes are involved in the development of AAA, including aortic wall inflammation, elastin breakdown, oxidative stress, smooth muscle cell (SMC) phenotypic switching and dysfunction, and extracellular matrix degradation. With open surgery being the only therapeutic option up to date, the lack of pharmaceutical treatment approach calls for identifying novel and effective targets and further understanding the pathological process of AAA. Both lifestyle and genetic predisposition have an important role in increasing the risk of AAA. Several cell types are closely related to the pathogenesis of AAA. Among them, vascular SMCs (VSMCs) are gaining much attention as a critical contributor for AAA initiation and/or progression. In this review, we summarize what is known about AAA, including the risk factors, the pathophysiology, and the established animal models of AAA. In particular, we focus on the VSMC phenotypic switching and dysfunction in AAA formation. Further understanding the regulation of VSMC phenotypic changes may provide novel therapeutic targets for the treatment or prevention of AAA.

Keywords: abdominal aortic aneurysm; apoptosis; extracellular matrix; inflammation; oxidative stress; phenotypic change; vascular smooth muscle cell.

Figure 1

Abdominal aortic aneurysm formation and its risk factors. Abdominal aortic aneurysm (AAA) occurs in the infra-renal segment with a diameter exceeding 3.0 cm. The risk factors, including male gender, aging, smoking, and hypercholesterolemia, etc., have been found to be related to AAA initiation and progression.

Figure 2

The pathophysiology of abdominal aortic aneurysm. The pathophysiology of abdominal aortic aneurysm (AAA) is a complicated process, involving the endothelial cell (EC) dysfunction with increased expression of adhesion molecules and chemokines, vascular smooth muscle cell (VSMC) phenotypic changes and dysfunction, inflammatory cell infiltration into the aortic wall, oxidative stress, and extracellular matrix (ECM) remodeling. Various mediators are involved in this process, including vascular cell adhesion molecule 1 (Vcam-1), monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), interleukin-1β (IL-1β), matrix metalloproteinases (MMPs), and tumor necrosis factor-α (TNF-α).