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Effects of nitric oxide in myocardial hypertrophy

Effects of nitric oxide in myocardial hypertrophy. By Li Xingzhe 90305111. Definition & Classification of myocardial hypertrophy. growth of the heart occurs by hypertrophy, i.e. increases in cardiac myocyte size

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Effects of nitric oxide in myocardial hypertrophy

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  1. Effects of nitric oxide in myocardial hypertrophy By Li Xingzhe 90305111

  2. Definition & Classification of myocardial hypertrophy • growth of the heart occurs by hypertrophy, i.e. increases in cardiac myocyte size • In pressure-overload hypertrophy, additional sarcomeres are assembled in parallel, leading to thicker myocytes and to a concentric pattern of ventricular hypertrophy. • In contrast, in volume overload hypertrophy, additional sarcomeres are assembled in series, leading to longer myocytes and ventricular dilatation (eccentric hypertrophy).

  3. Signaling pathways in pressure overload myocardial hypertrophy

  4. Signaling pathways in pressure overload myocardial hypertrophy

  5. Adaptive or maladaptive • Maladaptive signaling pathways: Gaq, Excessive Calcineruin-NFAT (?) • Adaptive signaling pathways: Melusin-GSK3(beta), MLP • No exact boundary exists between the two forms of pathways

  6. Categories of NOS • NOS1(nNOS)-sarcoplastic reticulum • NOS2(iNOS)-cytosol • NOS3(eNOS)-caveolae at cell membrane • Compartmentation • Constitutive / induced • Ca2+dependent/independent • All three expressed in myocardium

  7. Inhibition of cardiac hypertrophyby nitric oxide

  8. Inhibition of cardiac hypertrophyby nitric oxide

  9. Elevated expression of iNOS in hypertrophied myocardium

  10. Increased sensitivity of mitochondrial respiration to NO under hypertrophied condition

  11. Dual effects of nitric oxide in cardiac hypertrophy • NOS1(nNOS) and NOS3(eNOS) • low amounts of NO produced by NOS1 or NOS3 protect from maladaptive cardiac hypertrophy • Mainly through a NO-sGC-PKG axis • Target on Ca2+-calcineurin-NFAT pathway

  12. Dual effects of nitric oxide in cardiac hypertrophy • NOS2(iNOS) • exert primarily detrimental effects in the myocardium by promoting high-level NO and/or superoxide /peroxynitrite formation • Inhibition of MLP (an adaptive pathway) • Inhibition of mitochondrial respiration functions

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