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.
- SourceAvailable from: Noirin E Russell[show abstract] [hide abstract]
ABSTRACT: Cardiomyopathy is noted in up to 40% of infants of diabetic mothers, and the exact mechanisms are unknown. The aim of this study was to determine whether fetal serum markers of cardiac function differ between normal and type 1 diabetic pregnancies and to examine the relationship between these markers and fetal cardiac structure and function. This was a prospective observational study of 45 type 1 diabetic pregnancies and 39 normal pregnancies. All participants had concentrations of fetal pro-B-type natriuretic peptide (proBNP) and troponin-T (TnT) measured at the time of delivery. All patients with type 1 diabetes had Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus in the third trimester, and a subset (n = 21) had detailed fetal echocardiograms performed in each trimester. Fetal proBNP and TnT concentrations were higher in the diabetic cohort than in the normal cohort (P < 0.05). ProBNP correlated positively with interventricular septum thickness (P < 0.05) but not with cardiac function indexes in the third trimester. In patients with poor glycemic control, there was a significant positive correlation (P < 0.05) between fetal TnT and the third trimester umbilical artery pulsatility index. There were also increased levels of fetal TnT in infants with poor perinatal outcome (P < 0.05). Biochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome. Hyperglycemia in early pregnancy may affect myocardial and placental development, thus contributing to the susceptibility to hypoxia seen in these infants.Diabetes care 08/2009; 32(11):2050-5. · 8.09 Impact Factor