High levels of plasma
atrial natriuretic peptides (
ANP) are associated with pathological conditions such as
congestive heart failure (CHF). Recently, we have identified a cardiac
serine protease, corin, that is the pro-
ANP convertase. In this study, we examined the regulation of corin gene expression in cultured hypertrophic cardiomyocytes and in the left ventricular (LV) myocardium of a rat model of
heart failure. Quantitative RT-PCR analysis showed that both corin and
ANP mRNA levels were significantly increased in
phenylephrine (PE)-stimulated rat neonatal cardiomyocytes in culture. The increase in corin
mRNA correlated closely with the increase in cell size and
ANP mRNA expression in the PE-treated cells (r = 0.95, P < 0.01; r = 0.92, P < 0.01, respectively). The PE-treated cardiomyocytes had an increased activity in converting recombinant human pro-
ANP to biologically active
ANP, as determined by a pro-
ANP processing assay and a cell-based cGMP assay. In a rat model of
heart failure induced by
ligation of the left coronary artery, corin
mRNA expression in the noninfarcted LV myocardium was significantly higher than that of control heart tissues from
sham-operated animals, when examined by Northern blot analysis and RT-PCR at 8 wk. These results indicate that the corin gene is upregulated in hypertrophic cardiomyocytes and failing myocardium. Increased corin expression may contribute to elevation of
ANP in the setting of
cardiac hypertrophy and
heart failure.