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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的中心假设是去泛素酶UCH-L1是血管病变形成的基本调节因子。该提议将揭示一种新的机制，即UCH-L1作为组装炎症信号复合体的关键分子，从而微调血管炎症反应和病变形成。我们认为，这一结果将为理解血管病变形成中炎症的复杂后遗症提供新的见解。我们的假设将通过利用UCH-L1在体外和体内获得和丧失功能的方法来验证，以解决以下三个特定目标； 目的1.明确UCH-L1在体外调节VSMC炎症中的重要作用 目的2.明确UCH-L1介导的抑制VSMC炎症的分子机制 目的3.确定UCHL1在调节体内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