Collective transcriptomic deregulation of hypertrophic and dilated cardiomyopathy - Importance of fibrotic mechanism in heart failure.

Myocardial fibrosis reside a common pathological feature in hypertrophic and dilated cardiomyopathy that results in ventricular dysfunction leading to heart failure. Though several studies reported the role of fibrosis in cardiac diseases, their pathologic mechanisms leading to heart failure remains unclear. A few studies have proposed integrated analysis of microarray information and protein-protein interaction (PPI) systems to discover subnetwork markers related to diagnosis and prognosis of the disease. In addition to PPI networks, we incorporated miRNAs and transcription factors to find the putative miRNAs and transcription factors that might regulate the pathological process and progression of cardiomyopathy and their further progression to heart failure. The important submodules from network revealed the significance of Small Leucine Rich Proteoglycans (SLRPs), Extracellular matrix (ECM) related proteins and complement system in fibrosis. Sequence analysis of different SLRPs suggest that Keratocan and Fibromodulin possesses the same collagen binding site. A predicted mechanism of TGFβ1 shows the involvement of different pathway of HCM and DCM in progression of heart failure.