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.
Highlights
Aneurysm is the term for a dilated blood vessel with a diameter at least 1.5 times its normal size [1]
smooth muscle cell (SMC) could be induced by transforming growth factor-β (TGF-β), platelet-derived growth factor-BB (PDGF-BB), angiotensin II (Ang II), etc., and change into a dedifferentiated phenotype with low levels of contractile proteins but high levels of molecules associated with proliferation, migration, fibrosis, and inflammation [60,63,64,65]
In a study exploring the effects of calorie restriction on Abdominal aortic aneurysm (AAA) development, Sirtuin 1 (SIRT1) expression in vascular SMCs (VSMCs) was found critical for mediating the protective effects of calorie restriction against aortic aneurysm formation
Summary
Aneurysm is the term for a dilated blood vessel with a diameter at least 1.5 times its normal size [1]. The treatment option for patients with large (≥55 mm), rapidly growing (>10 mm), or symptomatic AAAs remains endovascular exclusion or open surgery [5], the postsurgical mortality for emergency operations stays at around 50% [12]. The ultrasound screening of the highrisk populations (men of 65-years and older) has been demonstrated to be an effective approach to prevent the AAA related mortality [10,11] It is costly and not appropriate for the assessment of AAA progression. The pathophysiology of AAA is complex, involving the increased expression of endothelial cell (EC) adhesion molecules and chemokines, the inflammatory cell infiltration into the aortic wall, vascular smooth muscle cell (VSMC) dysfunction, aortic extracellular matrix (ECM) remodeling, oxidative stress, and the formation of intraluminal thrombus (Figure 2) [3,6,13]. 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)
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