TY - JOUR T1 - Intrauterine growth restriction is associated with cardiac ultrastructural and gene expression changes related to the energetic metabolism in a rabbit model. JF - Am J Physiol Heart Circ Physiol Y1 - 2013 A1 - González-Tendero, Anna A1 - Torre, Iratxe A1 - García-Cañadilla, Patricia A1 - Crispi, Fátima A1 - Garcia-Garcia, Francisco A1 - Dopazo, Joaquin A1 - Bijnens, Bart A1 - Gratacós, Eduard KW - Animals KW - Disease Models, Animal KW - Energy Metabolism KW - Female KW - Fetal Growth Retardation KW - gene expression KW - Mitochondria KW - Myocardium KW - Oxidative Phosphorylation KW - Placenta KW - Pregnancy KW - Rabbits AB -

Intrauterine growth restriction (IUGR) affects 7-10% of pregnancies and is associated with cardiovascular remodeling and dysfunction, which persists into adulthood. The underlying subcellular remodeling and cardiovascular programming events are still poorly documented. Cardiac muscle is central in the fetal adaptive mechanism to IUGR given its high energetic demands. The energetic homeostasis depends on the correct interaction of several molecular pathways and the adequate arrangement of intracellular energetic units (ICEUs), where mitochondria interact with the contractile machinery and the main cardiac ATPases to enable a quick and efficient energy transfer. We studied subcellular cardiac adaptations to IUGR in an experimental rabbit model. We evaluated the ultrastructure of ICEUs with transmission electron microscopy and observed an altered spatial arrangement in IUGR, with significant increases in cytosolic space between mitochondria and myofilaments. A global decrease of mitochondrial density was also observed. In addition, we conducted a global gene expression profile by advanced bioinformatics tools to assess the expression of genes involved in the cardiomyocyte energetic metabolism and identified four gene modules with a coordinated over-representation in IUGR: oxygen homeostasis (GO: 0032364), mitochondrial respiratory chain complex I (GO:0005747), oxidative phosphorylation (GO: 0006119), and NADH dehydrogenase activity (GO:0003954). These findings might contribute to changes in energetic homeostasis in IUGR. The potential persistence and role of these changes in long-term cardiovascular programming deserves further investigation.

VL - 305 IS - 12 U1 - https://www.ncbi.nlm.nih.gov/pubmed/24097427?dopt=Abstract ER -