Molecular characterisation of neonatal cardiac hypertrophy and its regression

Abstract

Neonatal cardiac hypertrophy associated with diabetic pregnancy is transient and regresses naturally, but is associated with increased morbidity and mortality. This study was undertaken to analyse the changes in expression of 5 cardiac genes, including atrial natriuretic peptide, alpha- and beta-myosin heavy chain, and cardiac and skeletal alpha-actin genes, using a rat neonatal model, in which cardiac hypertrophy was induced via maternal diabetes. In the hypertrophied left ventricle of neonates from diabetic mothers, the levels of mRNA from all the above genes except skeletal alpha-actin were increased by between 1.8- and 12-fold compared with the controls at birth (p < 0.05). In the first 28 days, the level of mRNA for alpha-myosin heavy chain increased slightly, while that for atrial natriuretic peptide and beta-myosin heavy chain decreased continuously similar to the controls, but at a significantly faster rate. No significant difference between the two groups of neonates was observed in all 5 genes after 1 month, indicating complete regression. Expression of 5 cardiac genes in the neonatal cardiac hypertrophy was characterised in both hypertrophic and regressive phases. Hypertrophic regression provides a unique model for the testing of new drugs or genetic modifying factors in cardiac hypertrophy.

Troponin T and Pro–B-Type Natriuretic Peptide in Fetuses of Type 1 Diabetic Mothers

“…The role of NPR-A in inhibiting cardiac hypertrophy seems to be even more important in the presence of hypoxia (23). Gopinath et al (24) found that mRNA levels for the atrial natriuretic peptide gene were significantly higher in left ventricular tissue from neonates of diabetic mothers than from those control mothers, followed by an 18-fold decrease in mRNA from the 1st to the 28th neonatal day in comparison with a fivefold decrease in the control neonates during the same time with no difference between the cohorts by day 28. This model fits with the regression in diabetic cardiomyopathy that is usually seen in the postnatal period.…”

Increased fetal cardiac natriuretic peptide secretion in type‐1 diabetic pregnancies

“…In aryl hydrocarbon receptor-null mouse embryos that develop cardiac hypertrophy, atrial natriuretic factor gene expression is upregulated on 14.5 days gestation (22). In addition, studies on rats have shown that neonates from diabetic dams have significant cardiac hypertrophy and about 4-fold higher ventricular expression of ANP mRNA compared with control group neonates (12). They found about 18-fold decrease in ANP mRNA expression in the neonates of diabetic pregnancies from the 1st to the 28th day in comparison with a 5-fold decrease in the controls during the same period (12).…”

“…In addition, studies on rats have shown that neonates from diabetic dams have significant cardiac hypertrophy and about 4-fold higher ventricular expression of ANP mRNA compared with control group neonates (12). They found about 18-fold decrease in ANP mRNA expression in the neonates of diabetic pregnancies from the 1st to the 28th day in comparison with a 5-fold decrease in the controls during the same period (12). These experimental studies support our findings, which show significantly elevated NT-proANP and NT-proBNP concentrations in fetuses born to diabetic mothers.…”

“…They can reduce cardiac afterload and preload, and inhibit cardiac fibrosis and hypertrophy (11). Experimental studies on diabetic rats have shown an increase in fetal cardiac ANP and BNP levels, and an activation of ANP gene expression in the neonatal hypertrophied left ventricle (12, 13). In addition, increased umbilical cord proBNP levels were demonstrated in human infants of diabetic mothers with poor glycemic control (14).…”

Prematurity and low weight at birth as new conditions predisposing to an increased cardiovascular risk

“…The application of molecular biological techniques has provided evidence that the hearts of preterm neonates treated with corticosteroids feature an increase in alpha chains of myosin and a reduction in beta one, an event similar to that observed in the case of cardiac hypertrophy in neonates born from a diabetic mother. 70…”