EXPRESSION OF A-TYPE, B-TYPE, AND C-TYPE NATRIURETIC PEPTIDE GENES IN FAILING AND DEVELOPING HUMAN VENTRICLES - CORRELATION WITH EXPRESSION OF THE CA2+-ATPASE GENE

Brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are novel natriuretic peptides, originally isolated from porcine brain. Similar to atrial natriuretic peptide (ANP), BNP is also synthesized in and secreted from cardiocytes, but CNP is not expressed at significant levels in normal adult myocardium. Previous studies have indicated that the serum level and ventricular expression of the ANP gene were augmented in patients with heart failure. Recently, the serum level of BNP was also reported to increase in human heart failure. To examine whether or not the expression of these natriuretic peptides is regulated in ventricular myocardium in a concordant manner, we performed Northern blot analysis using total cellular RNA isolated from the diseased left ventricles of 30 cardiac transplant recipients with end-stage heart failure, seven ventricles from organ donors (control group), and two ventricles of artificially aborted 17- and 19-week-old fetuses. The levels of mRNAs encoding both BNP and ANP increased significantly (p<0.01) in the left ventricular myocardium from the patients with end-stage heart failure as compared with the control group. The levels of BNP mRNA correlated positively with those of ANP mRNA (r=0.73, p<0.01) and negatively with those of sarcoplasmic reticulum Ca2+-ATPase mRNA (r=-0.66,p<0.01) in the left ventricular myocardium from the patients with heart failure. There was also a negative correlation between the levels of ANP and the sarcoplasmic reticulum Ca2+-ATPase mRNAs (r=-0.65, p<0.01). In fetal myocardium, ventricular expression of ANP mRNA was higher and that of BNP mRNA was unchanged as compared with adult control myocardium. In contrast, CNP mRNA was not detectable by Northern blot analysis in either the normal, fetal, or diseased ventricular myocardium. These data suggest that ventricular expression of BNP and ANP mRNAs is concordantly regulated in patients with end-stage heart failure and that this coexpression of these two natriuretic peptides may play an important role in a compensatory process in human heart failure. In contrast, expression of BNP and ANP is discordantly regulated in the fetal ventricles, and CNP is probably never expressed at the significant level detectable by Northern blot analysis in the ventricles either during development or in disease states.