%0 Journal Article
%T Activated Protein C Has a Protective Effect against Myocardial I/R Injury by Improvement of Endothelial Function and Activation of AKT1
%A Yoshito Maehata
%A Shigeru Miyagawa
%A Yoshiki Sawa
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0038738
%X Objectives Activated protein C (APC) has a protective efficacy against ischemia-reperfusion (I/R) injury in several organs. The objective of this study was to investigate effect of APC in myocardium with possible mechanism. Methods We used regional and global myocardial I/R injury models of rats. They consisted of I/R injuries (1) by ligation of left coronary artery, or (2) using Langendorff apparatus. Langendorff was used to focus the mechanism of APC excluding coagulation cascade in a working heart. Each experiment had an APC group (n = 10) and a control group with normal saline (n = 10). Injections of these solutions into rats were performed 30 minutes before the planned-I/R injury. Cardiac performance after the procedure was evaluated by echocardiography or indices with Langendorff apparatus. Coronary flow (CF) was measured in the global I/R injury model. Western blotting was performed to detect the change of AKT1 signal in myocardium after global I/R injury. Results LV function improved significantly in the APC group: %EF at 2 weeks after procedure, 70.8%¡À4.5% vs. 56.5%¡À0.7%; APC vs. control; p<0.01. Percent LV development pressure (LVDP) also improved in the APC group significantly, 88.8%¡À45.3% vs. 28.1%¡À15.4%; APC vs. control; p<0.01. In APC group, %CF improved significantly, 88.5%¡À15.8% vs. 65.0%¡À13.4%; APC vs. control; p<0.01. It was enhanced significantly when acetylcholine was administered; % CF: 103.5%¡À9.9% vs. 87.0%¡À12.1%; APC vs. control; p<0.05. Western blotting revealed that APC significantly induced activation of phosphorylated AKT1 in myocardium (p<0.05). Conclusions APC has a novel effect to protect myocardium and cardiac performance against I/R injury through improvement of endothelial function and activation of AKT1.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0038738