UBIQUITIN CARBOXYL TERMINAL HYDROLASE L1 (UCH-L1) AND VASCULAR LESION FORMATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 该项目的中心假设是去泛素化酶UCH-L1是血管病变形成的重要调节因子。该提案将揭示一种新的机制，即UCH-L1作为组装炎症信号复合物的关键分子，从而微调血管炎症反应和病变形成。我们认为，该结果将为了解血管病变形成中炎症的复杂后遗症提供新的见解。我们的假设将通过在体外和体内使用UCH-L1功能获得和丧失的方法来测试，以解决以下三个具体目标： 目标1.确定UCH-L1在体外调节VSMC炎症中的重要作用 目标2.明确UCH-L1介导的体外抑制VSMC炎症的分子机制 目标3：确定UCHL 1在体内调节VSMC炎症和血管病变形成中的重要作用

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The central hypothesis of the project is that deubiquitinating enzyme UCH-L1 is an essential regulator of vascular lesion formation. The proposal will uncover a novel mechanism that UCH-L1 serves as a key molecule in assembling inflammatory signaling complex thereby fine tuning vascular inflammatory responses and lesion formation. It is our view that the outcome will provide novel insight into the understanding of the complex sequelae of inflammation in vascular lesion formation. Our hypothesis will be tested by uitilzing UCH-L1 gain- and loss-of-function approaches in vitro and in vivo to address three specific aims as follows; Aim 1. Define an essential role of UCH-L1 in regulating VSMC inflammation in vitro Aim 2. Define molecular mechanism of UCH-L1-mediated inhibition of VSMC inflammation in virto Aim 3. Determine an essential role of UCHL1 in regulating VSMC inflammation and vascular lesion formation in vivo