The role of the lectin pathway of complement activation in cardiac ischemia-reperfusion injury

The amount of injury caused by heart attacks is the main determinant of outcome and survival. The size of the artery that is blocked and how quickly it is opened again after the onset of the heart attack is an important factor in determining the amount of injury. However, it is now clear that another form of injury also occurs, paradoxically at the time when the blood supply is restored. This is called ischaemia-reperfusion injury. The precise cause of this type of injury is not known although there is evidence that activation of a system in the blood called the complement system by a pathway called the lectin pathway plays a role. We have developed a unique model to investigate the role of this pathway in ischaemia-reperfusion injury. The proposed studies will provide definitive information on the importance of this pathway in causing ischaemia-reperfusion injury and whether inhibiting this system would be valuable way of protecting the heart after heart attacks.

The purpose of this application is to clarify the role of a protein known as MASP-2 in myocardial ischaemia reperfusion injury. MASP-2 is the key component of the only recently discovered lectin pathway of complement activation. A number of circumstantial observations indicate the Lectin pathway maybe invovled in ischaemia reperfusion injury. Within this application we will use a number of unique and novel reagents to build on our preliminary data. These agents will categorically determine the contribution of the Lectin pathway and MASP-2 to myocardial infarction and post-infarction remodelling.