Fibroblast-specific protein-protein interactions for myocardial fibrosis from MetaCore network

Abstract

Myocardial fibrosis is a major pathologic disorder associated with a multitude of cardiovascular diseases (CVD). The pathogenesis is complex and encompasses multiple molecular pathways. Integration of fibrosis-associated genes into the global MetaCore network of protein-protein interactions (PPI) offers opportunities to identify PPI with functional and therapeutic significance. Here, we report the generation of a fibrosis-focused PPI network and identification of fibroblast-specific PPI driving reparative and reactive myocardial fibrosis. In TGFb-mediated fibroblast activation, PPI hubs predict new regulatory mechanisms for fibrosis-associated genes. We introduce an efficient Erdos barrage approach to suppress activation of a number of fibrosis-associated nodes in order to reverse fibrotic cascades. Our results suggest that PPI prediction model can offer network insights into fibrosis mechanisms and can complement future experimental efforts to counteract cardiac fibrosis.