Expression of the Atrial Natriuretic Peptide Gene in Human Fetal Heart*

Abstract

Expression of the human atrial natriuretic peptide (hANP) gene was examined in tissues of 19 to 28-week-old human fetuses. As expected the fetal atria express the hANP gene at a high level, accruing substantial quantities of ANP immunoreactivity and ANP mRNA. The neonatal ventricle also expresses the hANP gene at a significant level. ANP mRNA levels in the ventricle were, on the average, about 20% of those in the right atria. ANP immunoreactivity in ventricle was less that 5% of that in the right atria, suggesting important differences in the way these tissues synthesize and store the ANP peptide. Much lower levels of hANP transcripts were also detected in the lung and aortic arch. Analysis of the 5' termini of cardiac hANP transcripts using three independent techniques suggests the presence of two transcription start sites. A major start site is located approximately 28 basepairs downstream from the primary TATA sequence. A second minor start site is positioned about 110 basepairs further upstream. Immunocytochemistry and in situ hybridization analysis indicate that the hANP gene is expressed in a homogeneous distribution throughout the atrial myocardium. Diffuse low level expression is also present within the ventricular myocardium. In addition, there are scattered foci of increased expression in the ventricle which tend to be concentrated in the subendocardium of that organ. These findings indicate that the developing human ventricles as well as the atria possess the capacity to express the hANP gene at a substantial level and suggest that the ventricle may contribute significantly to the circulating pool of plasma ANP.

Effect of phorbol ester on the release of atrial natriuretic peptide from the hypertrophied rat myocardium

“…ANP granules, similar to those in atria, have been found within human foetal ventricles (Gardner et al, 1989) and neonatal rat ventricles (Thompson et al, 1986). The expression of the ANP gene decreases rapidly after birth and remains low, and often undetectable, in normal adult ventricles .…”

“…Several recent studies have demonstrated that rat (Bloch et al, 1986;Wei et al, 1987;Wu et al, 1988) and human (Tsuchimochi et al, 1988;Gardner et al, 1989) ventricular myocytes can synthesize ANP during the very early neonatal or foetal periods. ANP granules, similar to those in atria, have been found within human foetal ventricles (Gardner et al, 1989) and neonatal rat ventricles (Thompson et al, 1986).…”

“…Biosynthesis of ANP also occurs in other tissues, particularly in cardiac ventricles (Gutkowska & Nemer, 1989). Ventricular expression of the ANP gene is high in the late foetal and early neonatal period (Bloch et al, 1986;Wei et al, 1987;Zeller et al, 1987;Tsuchimochi et al., 1988;Wu et al, 1988;Gardner et al, 1989), decreases rapidly after birth (Bloch et al, 1986;Wei et al, 1987;Gardner et al, 1989) and remains low in the adult ventricle. ANP gene expression in the adult ventricle, however, has been shown to be activated in patients with congestive heart failure (Tsuchimochi et al, 1988;Edwards et al, 1988;Saito et al, 1989) and in animal models of cardiac hypertrophy Gutkowska & Nemer, 1989).…”

Divergent pathways mediate the induction of ANF transgenes in neonatal and hypertrophic ventricular myocardium.

“…Previous studies have documented that ventricular myocardium expresses relatively high levels of ANF during embryonic development and in the neonatal period (55)(56)(57)(58)(59). Shortly after birth, the expression of the ANF gene in the ventricle is downregulated, resulting in restricted expression of the ANF gene primarily to the atria.…”

Human fetal cardiovascular profile score and neonatal outcome in intrauterine growth restriction

“…Neonates with a CVP score ≤ 6 had significantly higher NT-proANP levels than had those with higher CVP scores. NT-proANP levels reflect distention of the fetal cardiac chambers and correlate with increased venous pressure 15,22 . Accordingly, we found that fetuses with umbilical venous pulsations demonstrated significantly higher NT-proANP levels than did fetuses with nonpulsatile umbilical venous flow.…”