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 • 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).
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
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
Increased sensitivity of mitochondrial respiration to NO under hypertrophied condition
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
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