Cardiovascular disease (CVD) remains the leading cause of worldwide mortality and the total costs of CVD, direct and indirect, are greater than any other diagnostic group. Most pathophysiological cardiac conditions are associated with development of myocardial fibrosis. Accumulation of extracellular matrix results in increased ventricular stiffness and disrupts the normal electrical cell-to-cell coupling and impulse conduction predisposing to arrhythmias and sudden cardiac death. TGFß1 is the central regulator of fibrotic processes in the heart and signals via canonical SMAD signaling pathways. TGFß1 also signals via non-canonical pathways, such as MAP kinase and PI3k/AKT signaling pathways that are activated by a variety of receptor tyrosine kinases (RTKs) and their ligands. Our aim is to investigate if targeting the feedback regulation of RTK signaling can restrict excessive TGFß1 signaling and reduce development of myocardial fibrosis and heart failure.

2025

2029