title: Signalling processes in endothelial ageing in relation to chronic oxidative stress and their potential therapeutic implications in humans.
abstract: Ageing is an important risk factor for the development of cardiovascular diseases. Vascular ageing is mainly characterized by endothelial dysfunction, an alteration of endothelium-dependent signalling processes and vascular remodelling. The underlying mechanisms comprise increased production of reactive oxygen species (ROS), inactivation of nitric oxide (.NO) and subsequent formation of peroxynitrite (ONOO(-)). Elevated ONOO(-) may exhibit new messenger functions by post-translational oxidative modification of intracellular regulatory proteins. Mitochondria are a major source of age-associated superoxide formation, as electrons are misdirected from the respiratory chain. Manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, is an integral part of the nucleoids and may protect mitochondrial DNA from ROS. A model linking .NO, mitochondria, MnSOD and its acetylation/deacetylation by sirtuins (NAD+-dependent class III histone deacetylases) may be the basis for a potentially new powerful therapeutic intervention in the ageing process.
authors.affiliation: Clinic of Cardiology, Cardiovascular Centre, Department of Medicine, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland. bernd.vanderloo@usz.ch
authors.forename: Bernd
authors.initials: B
authors.lastname: van der Loo
authors.forename: Stefan
authors.initials: S
authors.lastname: Schildknecht
authors.forename: Rebecca
authors.initials: R
authors.lastname: Zee
authors.forename: Markus M
authors.initials: MM
authors.lastname: Bachschmid
mesh_terms: D016922:Cellular Senescence / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D008928:Mitochondria / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D037761:Sirtuins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D037761:Sirtuins