Signalling processes in endothelial ageing in relation to chronic oxidative stress and their potential therapeutic implications in humans.
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.
van der Loo
Bernd
B
Clinic of Cardiology, Cardiovascular Centre, Department of Medicine, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland. bernd.vanderloo@usz.ch
Schildknecht
Stefan
S
Zee
Rebecca
R
Bachschmid
Markus M
MM
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
D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D037761:Sirtuins