Role of Netrin-4 during Myocardial Ischemia Reperfusion Injury

点击翻译按钮获取中文摘要

Myocardial ischemia reperfusion is the most prominent form of Ischemia-Reperfusion injury (IR) and is associated with significant mortality. During IR injury of the heart neutrophils infiltrate the affected areas, enhance tissue inflammation and as such increase tissue injury. Recent work by us has shown that not only the classical cytokine/ chemokine system guides leukocyte migration but also the system of neuronal guidance proteins. However, not much is known about the role of Netrin-4 (Ntn4) during myocardial IR injury. In preliminary experiments we found that genetic deletion of Ntn4 significantly alters neutrophil migration and that Ntn4 levels affect the extent of myocardial tissue injury following reperfusion. Therefore, we propose here in this project to decipher the role of Ntn4 during myocardial IR injury. We will investigate the role of Ntn4 tissue specific expression for immune cell recruitment, tissue inflammation and platelet-neutrophil complex formation. Next, we will use tissue specific deletion of Ntn4 in erythrocytes, endothelial cells, myocardial and lysozyme positive cells to identify the origin and impact of Ntn4 for myocardial tissue injury. This will provide novel evidence into the role of the Ntn4 during conditions associated with tissue inflammation and IR. Future therapies for myocardial IR injury and several other conditions associated with IR might be based on these findings.