Elucidation of Molecuolar Mechanism for Cardioprotection-Study from Genetic Engineered Mice

点击翻译按钮获取中文摘要

Accumulating evidence indicates that the natriuretic peptide system plays roles in cardiac remodeling in chronic stage. In the present study we examined effects of high plasma concentration of BNP in acute remodeling after acute myocardial infarction (AMI) in mice overexpressing BNP in the liver, and also effects of target disruption of the gene encoding GC-A, a common receptor for ANP and BNP in ischemia reperfusion injury.Experiment 1 using BNP transgenic mice : Mice overexpressing BNP showed low survival rate after permanent occlusion of left coronary artery during first 7 days, compared with wild type mice. High mortality was due to higher incidence of free wall rupture accompanied by more abundant infiltration of polymorphnuclear leucocytes. Expression of membrane metalloprotease 9 mRNA was higher in BNP transgenic mice than wild type mice.Experiment 2 using mice lacking GC-A gene : AMI remains the leading cause of death in civilized countries. Although reperfusion of coronary arteries reduces mortality, it is associated with tissue injury that shares many characteristics with inflammatory responses. Endothelial P-selectin-mediated infitration of neutrophils plays a key role in the "reperfusion injury". However, the mechanism of the P-selectin induction is not known. Here, we show that infarct size after ischemia-reperfusion was significantly smaller in mice lacking guanylyl cyclase (GC)-A, a natriuretic peptide receptor. The decrease was accompanied by decreases in neutrophil infiltration, in coronary endothelial P-selectin expression.These two experiments provide new roles of ratriuretic peptide system in AMI.