Effects of Exogenous Recombinant APC in Mouse Models of Ischemia Reperfusion Injury and of Atherosclerosis

Karin C. A. A. Wildhagen; Roy Schrijver; Linda Beckers; Hugo ten Cate; Chris P. M. Reutelingsperger; Esther Lutgens; Gerry A. F. Nicolaes

doi:10.1371/journal.pone.0101446

Effects of Exogenous Recombinant APC in Mouse Models of Ischemia Reperfusion Injury and of Atherosclerosis

Karin C. A. A. Wildhagen, Roy Schrijver, Linda Beckers, Hugo ten Cate, Chris P. M. Reutelingsperger, Esther Lutgens, Gerry A. F. Nicolaes^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Activated protein C (APC) is a serine protease that has both anticoagulant and cytoprotective properties. The cytoprotective effects are protease activated receptor 1 (PAR-1) and endothelial protein C receptor (EPCR) dependent and likely underlie protective effects of APC in animal models of sepsis, myocardial infarction and ischemic stroke. S360A-(A) PC, a variant (A) PC that has no catalytic activity, binds EPCR and shifts pro-inflammatory signaling of the thrombin-PAR-1 complex to anti-inflammatory signaling. In this study we investigated effects of human (h) wt-PC, hS360A-PC, hwt-APC and hS360A-APC in acute (mouse model of acute myocardial ischemia/reperfusion (I/R) injury) and chronic inflammation (apoE(-/-) mouse model of atherosclerosis). All h(A) PC variants significantly reduced myocardial infarct area (p

Original language	English
Article number	e101446
Journal	PLOS ONE
Volume	9
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0101446
Publication status	Published - 17 Jul 2014

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10.1371/journal.pone.0101446Licence: CC BY

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title = "Effects of Exogenous Recombinant APC in Mouse Models of Ischemia Reperfusion Injury and of Atherosclerosis",

abstract = "Activated protein C (APC) is a serine protease that has both anticoagulant and cytoprotective properties. The cytoprotective effects are protease activated receptor 1 (PAR-1) and endothelial protein C receptor (EPCR) dependent and likely underlie protective effects of APC in animal models of sepsis, myocardial infarction and ischemic stroke. S360A-(A) PC, a variant (A) PC that has no catalytic activity, binds EPCR and shifts pro-inflammatory signaling of the thrombin-PAR-1 complex to anti-inflammatory signaling. In this study we investigated effects of human (h) wt-PC, hS360A-PC, hwt-APC and hS360A-APC in acute (mouse model of acute myocardial ischemia/reperfusion (I/R) injury) and chronic inflammation (apoE(-/-) mouse model of atherosclerosis). All h(A) PC variants significantly reduced myocardial infarct area (p",

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AU - Wildhagen, Karin C. A. A.

AU - Schrijver, Roy

AU - Beckers, Linda

AU - ten Cate, Hugo

AU - Reutelingsperger, Chris P. M.

AU - Lutgens, Esther

AU - Nicolaes, Gerry A. F.

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