Nitric oxide synthase in post-ischaemic remodelling: new pathways and mechanisms.
The three isoforms of nitric oxide synthase (NOS), spatially confined in specific intracellular compartments in cardiac cells, have distinct roles in the regulation of contractility in pathophysiological situations. Recently, evidence has emerged that implicates NOS in modulating myocardial remodelling during cardiac stress, including after ischaemic insults. As long as they remain in a coupled state the NOS mostly attenuate hypertrophic remodelling through both cGMP-dependent and independent mechanisms. We review the evidence provided from the phenotype of genetic mouse models as well as from in vitro cell experiments dissecting the signalling effectors involved in the NOS-mediated regulation that justify new therapeutic interventions on the NOS-cGMP axis to attenuate the development of heart failure.
Pole of Pharmacology and Therapeutics, Institut de Recherche Experimentale et Clinique, Brussels, Belgium.
Boris
B
Manoury
Virginie
V
Montiel
Jean-Luc
JL
Balligand
D000818:Animals; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D015398:Signal Transduction; D020257:Ventricular Remodeling / Q000502:physiology*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase