Natriuretic Peptides and Cell-based Therapy for Heart Failure

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The overall objective of this resubmitted project remains focused on the establishment of a cell based technique to prevent progressive left ventricular (LV) dysfunction in a dog model of heart failure using an intracoronary infusion of genetically-modified autologous blood outgrowth endothelial cells that express brain natriuretic peptide (BNP). The natriuretic peptide system (NPS) plays an important physiological role in the humoral integration of the heart, kidney and vasculature to control sodium balance and arterial blood pressure, and there is emerging evidence that activation of this system is beneficial. Specifically, it is considered a compensatory endocrine response to LV dysfunction that maintains sodium balance without activating the renin-angiotensin-aldosterone system and increasing filling pressure. Presently, BNP has been approved for IV use in heart failure and there are clinical trials that are being conducted in Europe to investigate the therapeutic role of endothelial progenitor cells (EPCs) in myocardial ischemia and in nonischemic left ventricular (LV) dysfunction. Thus this application?s significance is that it addresses an important clinical problem using a promising cellular and genetic approach.