主动脉夹层和主动脉瘤发病隐匿、起病凶猛，为我国常见危急重症。但因发病机制不清，尚缺乏有效防治药物。细胞外基质金属蛋白酶诱导子（EMMPRIN, basigin, CD147) 不但能显著诱导多种细胞基质金属蛋白酶产生，更是炎症反应的关键介导因子。我们首次发现EMMPRIN在人主动脉瘤（尤其合并主动脉夹层）中表达上调，提示EMMPRIN可能是该类疾病发病的中间关键蛋白。但抑制EMMPRIN对主动脉夹层及主动脉瘤发生的影响及其相关调控机制仍不明确。本项目将利用我们成功构建的新主动脉瘤破裂模型及主动脉夹层模型，研究EMMPRIN信号抑制对急性主动脉夹层和主动脉瘤破裂发生、发展及血管病理重构的影响，阐明EMMPRIN在血管细胞相互作用及炎症反应中的介导作用，揭示EMMPRIN在急性主动脉夹层和主动脉瘤破裂形成中的关键作用及炎症级联反应相关调控机制，为探索新的预防和治疗方法提供科学根据。

Aortic dissection and aortic aneurysms are serious conditions, which are becoming a relatively common cause of death in China. There is lack of available drug therapies due to undefined molecular mechanisms. Aortic aneurysmal diseases are characterized by chronic inflammation related vascular remodeling. EMMPRIN (extracellular matrix metalloproteinase inducer; also known as basigin and CD147) is a cell-surface glycoprotein that has been increasingly realized to be a key mediator of inflammation in addition to its classical functions on MMP induction. .We are the first to report the increased abundance of EMMPRIN in human thoracic or abdominal aneurysmal aortas, especially in aortic tissues having both aneurysms and dissection. The results imply that EMMPRIN inhibition in vivo may reduce the propensity of the aorta to dilate and rupture, highlighting this protein as a potential new therapeutic target in patients with aortic aneurysmal diseases. However, a cause-and-effect relationship between EMMPRIN expression and aortic dissection and aneurysm formation cannot be made because specimens were obtained only in patients with advanced disease. Additionally, the regulatory mechanism of EMMPRIN in the development of aneurysmal disease remains unclear. In our preliminary study, we demonstrated that EMMPRIN expression in cultured aortic smooth muscle cells could be enhanced by AngII stimulation. .On the basis of the evidence from the literature and our preliminary data, we aimed to determine the effect of EMMPRIN deficiency in the development of AngII-induced aortic dissection in this proposal. In addition, to exam the EMMPRIN related mechanism underlying aortic rupture, a new aortic aneurysm mouse model will be used, in which a combination of Ang II infusion and transforming growth factor–β1 (TGF-β1) inhibition results in aortic aneurysm formation with significantly increased incidence of aortic rupture. We will also determine whether the role of EMMPRIN in the development and rupture of aortic aneurysm is through an inflammation dependent mechanism.