eNOS in the Heart



eNOS is expressed in multiple non-endothelial tissues, where the enzyme is involved in processes as diverse as neurotransmission and the modulation of cardiac myocyte function. We recently discovered that hydrogen peroxide plays a critical role in receptor-dependent modulation of eNOS and other signaling proteins in cardiac myocytes.


  • Sartoretto J, Kalwa H, Romero N, and Michel T.  In vivo imaging of NO and H2O2 in cardiac myocytes.  Methods in Enzymology 2013, 528:61-78. PMID:23849859. PDF
  • Sartoretto JL, Kalwa H, Shiroto T,  Pluth M, Lippard S and Michel T.  Role of Ca2+ in the control of H2O2-modulated phosphorylation pathways leading to eNOS activation in cardiac myocytes. PLOS ONE  2012, 7(9): e44627. doi:10.1371/journal.pone.0044627. PDF
  • Sartoretto J, Kalwa H, Pluth M, Lippard S and Michel T.  Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis.  Proc Natl Acad Sci USA 2011, 108: 15792-15797. PDF
  • Sartoretto J, Jin B, Bauer M, Gertler F, Liao R and Michel T. Regulation of VASP phosphorylation in cardiac myocytes: Differential regulation by cyclic nucleotides and modulation of protein expression in diabetic and hypertrophic heart. Am J Physiol Heart Circ Phys 2009, 297:H1697-H1710. PDF
  • Feron O, Dessy C, Opel DJ, Arstall M, Kelly RA, Michel T. Modulation of the endothelial nitric oxide synthase-caveolin interaction in cardiac myocytes: implications for the autonomic regulation of heart rate. J Biol Chem. 1998;273:30249-54. PDF
  • Feron O, Smith TW, Michel T, Kelly RA. Dynamic targeting of the agonist- stimulated m2 muscarinic cholinergic acetylcholine receptor to caveolae in cardiac myocytes. J Biol Chem. 1997;272:17744-8. PDF
  • Feron O, Belhassen L, Kobzik L, Smith TW, Kelly RA, Michel T. Endothelial nitric oxide synthase targeting to caveolae: specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J Biol Chem. 1996;271:22810-4. PDF
  • Balligand JL, Kobzik L, Han X, Kaye DM, Belhassen L, O’Hara DS, Kelly RA, Smith TW, Michel T. Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes. J Biol Chem. 1995;270:14582-6. PDF
  • Balligand JL, Ungureanu-Longrois D, Simmons W, Kobzik L, Lamas S, Lowenstein C, Kelly RA, Smith TW, Michel T. Induction of NO synthase in rat cardiac microvascular endothelial cells by IL-1 beta and IFN-gamma. Am J Physiol. 1995;268:H1293-303. PDF
  • Balligand JL, Ungureaunu-Longrois D, Simmons W, Lowenstein C, Malinski T, Kelly RA, Smith TW, Michel T. Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes: characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro. J Biol Chem. 1994;169:27580-8. PDF
  • Balligand JL, Kelly RA, Marsden P, Smith TW, Michel T. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc Natl Acad Sci USA. 1993;90 (1):347-51. PDF