OC26.03: Bioinformatic analysis of genes regulating myocardiocyte contractile function in a rabbit model of cardiac dysfunction due to intrauterine growth restriction

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To assess the existence of functional differences in blocks of genes regulating key steps in the contractile machinery of the myocardiocyte in a rabbit model of cardiac dysfunction due to fetal growth restriction (FGR). A FGR model was created in 5 pregnant rabbits, 40–50% of uteroplacental vessels of one horn were ligated at 25d of gestation, and cesarean section was performed at 30d. Fetal cardiac function assessment was performed in 15 cases and controls before delivery including: ductus venosus (DVPI) and aortic isthmus pulsatility index (AoIPI),left ejection fraction (EF) and isovolumetric relaxation time (IRT). After delivery, hearts of 6 pairs of cases and controls were selected at random and gene expression profile was analyzed with a rabbit DNA microarray in ventricular tissue. Genes involved in key elements of mycoardiocyte contractility, including calcium homeostasis and sarcomere contractiliy were analyzed with two kinds of bioinformatics analysis: differential single-gene expression analysis and FatiScan analysis to assess coordinated differences in blocks of genes involved in complex functions. DVPI, AoIPI and IRT were significantly increased in FGR (Table 1). FatiScan analysis demonstrated the sarcomeric M-band structure, including critical genes in sarcomere structure and function such as titin, obscuring and myomesisn, was significantly over-expressed in FGR versus healthy control hearts. Cardiac dysfunction in a rabbit model of FGR is associated with functional changes of genes regulating myocardiocyte contractility. Since these genes are also involved in genetic cardiomyopathies, these findings support further research to elucidate the presence of epigenetic changes leading to permanent cardiac dysfunction in FGR.

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