旗语家族分子(Semaphorins)最早被发现是调控神经生长的导向分子，然而，近来的研究表明参与多种生理病理功能。我们继报道了Sema4D参与动脉粥样硬化后，最近又发现该家族的另一成员Sema7A在血管扰动流区域的内皮细胞高表达，并且敲除Sema7A可延缓脉粥样硬化斑块的形成，提示了旗语家族成员参与动脉粥样硬化的全新机制。本课题将利用多种基因工程动物、动脉粥样硬化和血管损伤模型，以及现代细胞分子生物学技术，重点研究Sema7A响应扰动流、调控白细胞浸润、介导斑块内细胞间相互作用，以及调控斑块破裂后血栓形成的机制。并开展基于Sema7A的生物制剂开发和动脉粥样硬化干预的实验研究。本课题还将与美国宾夕法尼亚大学Lawrence F. Brass研究团队合作，利用其在本领域研究的国际领先优势和必要的高端技术，致力于阐明Sema7A在动脉粥样硬化发病中的作用机制。

Semaphorin family is a group of proteins that were originally identified as guidance proteins for neuronal growth. However, more studies showed that they participate a variety of pathophysiological functions. After reporting the role of a semaphorin family member, Sema4D, in atherosclerosis, we recently found that other member of this family called Sema7A was upregulated in endothelial cells of vascular wall where disturbed blood flow occurs and that deletion of Sema7A reduces plaque formation in hyperlipidemic atherosclerotic mice, implying a novel mechanism by which some semaphorins may play a role in atherogenesis. In this proposal, we will focus our studies on the mechanism of Sema7A upregulation in response to a disturbed blood flow, the mechanism of Sema 7A in mediating platelet-endothelial interactions for leukocyte infiltration, the role of Sema7A and its receptor α1β1 in cell-cell interaction network in the intimal interspace and the role of Sema7A in the thrombus formation in the setting of atherosclerosis. Translational studies on Sema7A for its potential as a target for the diagnostics and interference will be performed. We will also collaborate with the research team of Dr. Lawrence F. Brass at the university of Pennsylvania, the United States, taking advantage of the profound resources, such as necessary animal models and the-state-of art technologies e.g. intravital microscopic observation and analysis for pathological thrombus formation. The goal of this proposal is committed to clarify the role of Sema7A in the pathogenesis of the initiation and progression of atherosclerosis.