Abstract 19273: Fibroblast-Derived TSP1, via CD47, Upregulates Connective Tissue Growth Factor to Promote Left Ventricular Fibrosis and Heart Failure

Background: An estimated 5.5 million individuals in the United States have left ventricular heart failure (LV HF). Therapeutics, while relieving symptoms and extending life in some cases, cannot resolve this process. LV HF is characterized by excessive accumulation of the extracellular matrix. The causes of this process remain incompletely understood. Our team has recently described a widely expressed cell surface receptor CD47that is activated by its high affinity ligand, thrombospondin-1(TSP1) to promote LV HF. However, the role of TSP1- CD47signaling in promoting fibrosis, in general, and in the setting of LV HF, in specific, is unknown. Methods: Wild type mice expressing CD47and mutated mice lacking CD47( CD47null) were subjected to transverse aortic constriction (TAC) for 4 weeks followed by open chest pressure-volume loop analysis of cardiac hemodynamics. Signal transduction was confirmed in isolated left ventricles (LV) and normal human ventricular fibroblast cell culture systems. Results: In b...