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The Expression of Osteopontin and Autophagy-related Genes in Abdominal Aortic Aneurysm and the Molecular Mechanism of Osteopontin-induced Autophagy of Smooth Muscle Cells

Author: DuYaHao
Tutor: LiHuiHua
School: Beijing Union Medical College
Course: Pathology and Pathophysiology
Keywords: abdominal aortic aneurysm osteopontin smooth muscle cells autophagy
CLC: R543
Type: Master's thesis
Year: 2010
Downloads: 45
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Abstract


Abdominal aortic aneurysm (AAA) is a common vascular disease. Recently, the decreased smooth muscle cells (SMCs) and the alteration of extracellular matrix (ECM) have been known to be critical to the AAA formation.ECM maintains normal structure and function of abdominal aorta. Osteopontin (OPN) as a proinflammatory factor in ECM, is secreted by a variety of cells, including osteoclasts, activated macrophages, endothelial cells and SMCs. OPN induces the proliferation and apoptosis of SMCs. As the important component of tunica media in abdominal aorta, SMCs keep flexibility and mechanical resistance of arteries besides their contractile function. The decreasd SMCs result in degeneration of arteries. Recent studies have found that the apoptosis of SMCs decreased their quantity, and the apoptosis of SMCs in AAA was up-regulated. Autophagy is a well-conserved intracellular degradation process and plays an essential role in cell survival. However, whether the autophagy of SMCs was present in AAA was unclear. Furthermore, the effect of OPN on autophagy was not elucidated. Therefore, in this study we investigated (1) the expression of OPN and autophagy-related genes in AAA tissue; (2) the effects of OPN on autophagy especially the autophagy-related genes in SMCs and the molecular mechanism within it. The main results are as follow:1) The expression of OPN in AAA tissue was higher than normal aorta tissue.2) The autophagy-related genes including Atg4b, Beclinl, Bnip3 and VPS34 in AAA tissue were up-regulated compared with normal aorta.3) OPN induced occurrence of autophagy and the expression of autophagy-related genes in SMCs.4) p38 MAPK pathway functioned in OPN-induced autophagy in SMCs.In conclusion, our results demonstrated that the expression of OPN and autophagy-related genes in AAA tissue was significantly increased compared with normal aorta tissue and OPN induced the autophagy of SMCs by p38 MAPK signal pathway. This proposed mechanism provides important theoretical basis for the prevention and cure of the AAA formation.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Vascular disease
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