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Role of the Protein C System in Blood Vessel Repair

蛋白 C 系统在血管修复中的作用

基本信息

批准号：
7152762
负责人：
Lea M Beaulieu
金额：
$ 2.59万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2007-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7152762
关键词：
angiogenesis blood blood vessels chemotaxis emotions extracellular hemostatics intracellular model protease inhibitor protein C reperfusion role serine serine proteinases stroke

项目摘要

DESCRIPTION (provided by applicant): The protein C system is involved in the regulation of the coagulation pathway. Zymogen protein C (PC) binds to endothelial cell protein C receptor and is activated by thrombin (lla) bound to thrombomodulin. Activated protein C (APC) inactivates factors Va and Villa with protein S (PS), reducing further lla production. Recent work has studied the role of the protein C system in inflammation, sepsis, and stroke. APC is anti-inflammatory, anti-apoptotic, and able to increase recovery in stroke mouse models. The goal of this project is to study the role of the protein C system in the recovery after a stroke, focusing on the effects of APC on endothelial cell angiogenesis. It is hypothesized APC will increase invasion and chemotaxis of endothelial cells, resulting in an increase in angiogenesis and repair after a stroke. To test this hypothesis, first, transwell invasion, chemotaxis assays using HUVEC will be utilized to determine the effects of APC and the intracellular and extracellular events that are occurring. Second, it will be determined if the effects of APC can be regulated by serine protease inhibitors. Finally, using the tube formation and aortic ring models, the effects and regulation of APC in angiogenesis will be characterized.

描述（由申请人提供）：蛋白C系统参与凝血途径的调节。酶原蛋白C （Zymogen protein C， PC）与内皮细胞蛋白C受体结合，并被与凝血调节蛋白结合的凝血酶激活。活化蛋白C （Activated protein C， APC）用蛋白S （protein S， PS）灭活Va和Villa因子，进一步减少lla的产生。最近的工作研究了蛋白C系统在炎症、败血症和中风中的作用。APC具有抗炎、抗细胞凋亡的作用，并能促进脑卒中小鼠模型的恢复。本项目的目的是研究蛋白C系统在脑卒中后恢复中的作用，重点研究APC对内皮细胞血管生成的影响。假设APC会增加内皮细胞的侵袭和趋化性，导致中风后血管生成和修复的增加。为了验证这一假设，首先，将使用HUVEC进行跨井入侵、趋化试验，以确定APC的影响以及正在发生的细胞内和细胞外事件。其次，确定是否可以通过丝氨酸蛋白酶抑制剂调节APC的作用。最后，通过血管形成和主动脉环模型，探讨APC在血管生成中的作用和调控作用。