Role of the Protein C System in Blood Vessel Repair

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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.