前列腺素E2合酶在血管成形术后再狭窄发生中的作用

经皮冠状动脉成形术（PTCA）是一种广泛用于冠状动脉粥样硬化疾病治疗的有效方法，但其远期疗效受到术后血管再狭窄的限制，因此研究再狭窄的发生机制对提高PTCA的疗效有重要意义。研究表明前列腺素E2(PGE2)在血管稳态维持及损伤血管的修复中起重要的作用。然而，对控制PGE2合成的关键酶与血管损伤后再狭窄发生的关系至今尚无定论。本课题重点探讨PGE2合成酶（COX-1、COX-2及mPGES-1）与血管成形术后再狭窄发生、发展的关系，及基于它们的干预手段对再狭窄严重程度的影响。课题一将使用上述3种酶基因敲除、活性抑制或过表达手段研究它们在血管再狭窄发生中的作用；课题二将在培养小鼠血管平滑肌细胞（VSMCs）上研究COX-1、COX-2、mPGES-1表达活性对VSMCs增殖及迁移的影响及其分子机制。本课题的开展将为进一步阐明血管再狭窄的发生机理提供新的依据，也为该疾病的治疗提供新的思路。

Percutaneous transluminal coronary angioplasty (PTCA) has been widely used for treating coronary atherosclerosis. However, many patients undergoing PTCA experience post-angioplasty restenosis. An enormous amount of research has elucidated that PGE2 system is involved in the neointimal formation and vascular remodeling after vascular injury, which has greatly advanced our understanding of the mechanisms contributing to the pathogenesis of restenosis.The present studies are aimed to investigate the role of PGE2 synthesizing enzymes (COX-1, COX-2, mPGES-1) in the pathogenesis and development of restenosis, and to determine whether these enzymes could represent novel therapeutic targets. Specific aim #1 will examine the roles of COX-1, COX-2, mPGES-1 in the pathogenesis of restenosis by using gene deficient mice, specific inhibitors and overexpressing adenoviruses. Specific aim #2 will study the effect of enzymatic activity of COX-1, COX-2, mPGES-1 on proliferation and migration of cultured vascular smooth muscle cells (VSMCs) and define the underlying molecular mechanisms. The completion of the present studies could help clarify the role of PGE2 in the pathogenesis and development of restenosis and lead to new strategies for effective prevention and treatment for restenosis.