Complement plays a pivotal role in the pathogenesis of myocardial ischemia/reperfusion (MI/R) injury. Numerous studies have demonstrated significant reduction in the degree of MI/R injury using therapies, which inhibit the complement system. Results from this lab show that inhibition of the complement system at the level of C5 significantly attenuates MI/R injury. However, the exact role of C5a versus C5b-9 complex in MI/R injury is unknown. In addition, the regulatory pathways downstream of C5a versus C5b-9 formation have not been elucidated. We hypothesize that C5b-9 (membrane attack complex) plays an extremely important role in MI/R. This research project will delineate the role of C5a and C5b-9 during MI/R injury by utilizing a multi faceted approach for investigating the contribution of C5b-9 and C5a. Furthermore, the molecular mechanisms involved in the deleterious effects of C5a and C5b-9 will be characterized by identifying genes, which are regulated by C5a and/or C5b-9, using microarray analysis. There is a strong potential for development of therapeutic molecules which provide protection from MI/R injury, based on the 'results obtained from this project.
