121,949 research outputs found
Genes, Geography and Geometry The "Critical Mass" in Hypertrophic Cardiomyopathy
No full textHCM is caused by mutations in one of a number of genes. Approximately 450 different mutations have been discovered in genes for functional/structural proteins in the sarcomere (13 related genes) and myofilaments. Most of the alterations are missense, with a single amino acid residue substituted for another. The majority of HCM molecular defects lie in genes encoding functional and regulatory sarcomeric proteins such as beta-myosin heavy chain , actin, cardiac troponin T and I, and tropomyosin, as well as structural proteins, ie, myosin binding protein C (MYBPC) and titin.2 Identifying the specific gene mutation underlying the disease in individuals has more than an etiological relevance, as specific gene mutations may contribute to the different phenotypic and functional outcomes in patients suffering from HCM
β2-receptors, NADPH oxidase, ROS and p38 MAPK: Another “radical” road to heart failure?
No full textPersistent 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
Forever young?: nerve growth factor, sympathetic fibers, and right ventricle pressure overload.
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β2-Adrenoceptors, NADPH oxidase, ROS and p38 MAPK: another 'radical' road to heart failure?
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