Abstract 13164: Differential Expression of Myocardial Pronatriuretic Peptide Convertases Furin and Corin in Experimental Heart Failure
Background: Natriuretic peptides (NPs) play important roles as cardiorenal protective peptides. ProNPs are non-functional precursors of active NPs. ProANP is processed to its active form by the proNP convertase corin, proBNP by corin and furin, and proCNP by furin. The expression of furin and corin in the heart and whether their expression changes with heart failure (HF) or NP levels remains unknown.
Hypothesis: Gene and protein expression of corin and furin is present in the normal canine heart and increases in a canine model of HF.
Methods: Normal (n=4) and HF (n=5) dogs were examined. Experimental HF was produced by rapid right ventricular pacing at 240 bpm for 10 days. Cardiovascular function and neurohumoral factors were assessed. Furin and corin protein expression in normal canines were determined by Immunohistochemistry. Gene expression of NPs, furin, and corin in heart tissue were determined by quantitative RT-PCR.
Results: Pacing induced HF was characterized by decreased cardiac output, increased systemic vascular resistance, right atrial pressure, and pulmonary capillary wedge pressure, a significant increase in plasma ANP and cGMP levels (p<0.05), and trend for higher plasma BNP. Immunostaining revealed expression of corin and furin protein in all chambers of the normal canine heart. In HF left atrium (LA) and right atrium (RA), we observed that ANP, BNP, and CNP gene expressions were increased (p<0.05), as was furin gene expression (p<0.05), whereas corin gene was decreased (LA; p<0.05, RA; p=0.08). In left ventricle and right ventricle, there was no significant difference in NPs, furin, or corin gene expression in HF.
Conclusions: Furin and corin are widely present in the normal canine heart, but gene expression levels of these proNP convertases display opposing expression patterns, especially in the atrium of rapid pacing induced HF. This interesting selective change of furin and corin may have significance in the regulation of NP processing and ultimate cardiorenal function.
- © 2010 by American Heart Association, Inc.