Persistent activation of the cardiac b-adrenergic system may contribute to the pathogenesis of congestive heart failure. Both b1- and b2-adrenoceptors are known to mediate these noxious effects, yet the b1-adrenoceptor-PKA axis has received greater attention with less information available on b2-adrenoceptor driven pathways. In the present issue, Xu and colleagues provide new evidence, showing that b2-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 b2-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.
beta(2)-Adrenoceptors, NADPH oxidase, ROS and p38 MAPK: another 'radical' road to heart failure?
Di Lisa Fabio;Kaludercic Nina;
2011
Abstract
Persistent activation of the cardiac b-adrenergic system may contribute to the pathogenesis of congestive heart failure. Both b1- and b2-adrenoceptors are known to mediate these noxious effects, yet the b1-adrenoceptor-PKA axis has received greater attention with less information available on b2-adrenoceptor driven pathways. In the present issue, Xu and colleagues provide new evidence, showing that b2-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 b2-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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
