1,721,082 research outputs found
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
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
Death of an antioxidant brings heart failure with preserved ejection fraction to life: 5-oxoproline and post-ischaemic cardio-renal dysfunction
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Lymphocyte traffic changes induced by monolateral vagal denervation in mouse thymus and peripheral lymphoid organs
No full textIn this report we show that after monolateral vagal denervation (vagotomy), performed at the cervical level, a transient effect, lasting about 24 h, was produced on lymphocyte release from mouse thymus to peripheral lymphoid organs (spleen and lymph nodes). Labelling thymocytes in situ with fluorescein isothiocyanate (FITC) we note that the export of immature cells, CD4+CD8+, double positive (DP), and double negative, CD4-CD8- (DN), from the thymus was consistently increased 24 and 48 h after vagotomy. Double staining with anti-L3T4 (CD4) and anti-mouse CD8α showed that the number of DP and DN cells was significantly higher in both spleen and lymph nodes of vagotomized mice compared to controls (sham-operated), whereas the percentage of CD4+CD8- and CD8+CD4-, single positives (SP), was decreased. Considering thymic cellularity and apoptotic values, we exclude the non-specific effect of stress and suggest that this phenomenon could be in part due to a transient lack of the facilitating influence exerted by vagal efferent fibers on lymphocyte traffic at the cortico-medullary junction of the thymic gland, where mature cells, SP, leave the thymus to enter systemic circulation
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