caa a22 4500 475833228 CHVBK 20180406123846.0 cr unu---uuuuu 170329e20000201xx s 000 0 eng 10.1023/A:1007887020332 doi (NATIONALLICENCE)springer-10.1023/A:1007887020332 Coordinate Regulation of Metabolic Enzyme Encoding Genes During Cardiac Development and Following Carvedilol Therapy in Spontaneously Hypertensive Rats [Elektronische Daten] [Michael Sack, Louise Harrington, Anne Jonassen, Ole Mjøs, Derek Yellon] Fuel substrate utilization is highly regulated during cardiac development and with the onset of cardiac hypertrophy. Glucose and lactate are the predominant fuel substrates utilized during cardiac development. Postnatally, a switch occurs so that fatty acids become the chief energy substrate in the nonfed adult mammalian heart. A reversion back towards fetal energy metabolism occurs with the development of cardiac hypertrophy. To evaluate the role of this substrate preference switch in the development of cardiac hypertrophy, the molecular regulation directing these switches is being explored. Thus, we have begun by defining the temporal expression patterns of genes encoding key rate-controlling enzymes directing major fuel substrate metabolism during cardiac development, with pressure-overload-induced cardiac hypertrophy, and following antihypertensive therapy in spontaneously hypertensive rats. The genes encoding the fatty acid and adult enriched rate-controlling glycolytic enzymes are expressed at low levels in the fetal and neonatal rat heart. The genes encoding these enzymes are significantly and coordinately upregulated (≥ 70%) in adult rat hearts compared to the fetal expression patterns. A reciprocal and coordinate downregulation (≥ 40% reduction) of the fatty acid and adult enriched glycolytic enzyme encoding genes are observed with the induction of pressure-overload-induced hypertrophy in spontaneously hypertensive rats compared to Wistar-Furth normotensive control rats. Antihypertensive therapy with carvedilol, a vasodilating α-and β-adrenoreceptor antagonist, attenuates this reversion of the metabolic gene expression pattern towards fetal levels compared to placebo-treated littermate controls. This coordinate developmental and hypertrophy-induced regulation of genes that encode enzymes controlling both fatty acid and glycolytic catabolic pathways in the heart implicates potential mutual/overlapping regulatory signaling proteins within their gene regulatory programs. These gene regulatory pathways need to be identified and modulated in order to characterize the functional role of fuel substrate metabolism in cardiac development and with the induction of cardiac hypertrophy. Kluwer Academic Publishers, 2000 cardiac hypertrophy nationallicence metabolic enzymes nationallicence gene regulation nationallicence spontaneously hypertensive rat nationallicence carvedilol nationallicence Sack Michael Hatter Institute for Cardiology Research, Department of Medicine, University of Cape Town Medical School, South Africa aut Harrington Louise The Hatter Institute for Cardiovascular Studies, University College London Hospitals & Medical School, London, U.K. aut Jonassen Anne Department of Medical Physiology, University of Trømso, Norway aut Mjøs Ole Department of Medical Physiology, University of Trømso, Norway aut Yellon Derek The Hatter Institute for Cardiovascular Studies, University College London Hospitals & Medical School, London, U.K. aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/1(2000-02-01), 31-39 0920-3206 14:1<31 2000 14 10557 https://doi.org/10.1023/A:1007887020332 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007887020332 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sack Michael Hatter Institute for Cardiology Research, Department of Medicine, University of Cape Town Medical School, South Africa aut NATIONALLICENCE 700 1- Harrington Louise The Hatter Institute for Cardiovascular Studies, University College London Hospitals & Medical School, London, U.K aut NATIONALLICENCE 700 1- Jonassen Anne Department of Medical Physiology, University of Trømso, Norway aut NATIONALLICENCE 700 1- Mjøs Ole Department of Medical Physiology, University of Trømso, Norway aut NATIONALLICENCE 700 1- Yellon Derek The Hatter Institute for Cardiovascular Studies, University College London Hospitals & Medical School, London, U.K aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/1(2000-02-01), 31-39 0920-3206 14:1<31 2000 14 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer