title: β₂-Adrenoceptors, NADPH oxidase, ROS and p38 MAPK: another 'radical' road to heart failure?
abstract: Persistent activation of the cardiac β-adrenergic system may contribute to the pathogenesis of congestive heart failure. Both β₁- and β₂-adrenoceptors are known to mediate these noxious effects, yet the β₁-adrenoceptor-PKA axis has received greater attention with less information available on β₂-adrenoceptor driven pathways. In the present issue, Xu and colleagues provide new evidence, showing that β₂-adrenoceptor over-expression leads to increased reactive oxygen species (ROS) emission, mainly caused by up-regulation of reduced nicotinamide adenine dinucleotide phosphate oxidase (Nox) 2 and 4. Increase in ROS levels is accompanied by p38 mitogen-activated protein kinase activation, fibrosis, apoptosis and cardiac dysfunction. Both Nox inhibition and administration of the antioxidant N-acetyl cysteine prevent these adverse effects. Interestingly, antioxidant treatment also prevents the increase in Nox expression, suggesting that β₂-adrenoceptor stimulation triggers a vicious cycle eventually amplified by both Nox isoforms. The possible existence of a circuitry to enhance ROS signalling and detrimental consequences on myocardial remodelling are also discussed, in light of the recent description of intracellular localization of Nox4.
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy. dilisa@civ.bio.unipd.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
authors.forename: Nina
authors.initials: N
authors.lastname: Kaludercic
authors.forename: Nazareno
authors.initials: N
authors.lastname: Paolocci
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D018343:Receptors, Adrenergic, beta-2; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases