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Signalling processes in endothelial ageing in relation to chronic oxidative stress and their potential therapeutic implications in humans
Author(s) -
Van Der Loo Bernd,
Schildknecht Stefan,
Zee Rebecca,
Bachschmid Markus M.
Publication year - 2009
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2008.043315
Subject(s) - peroxynitrite , oxidative stress , ageing , mitochondrion , microbiology and biotechnology , reactive oxygen species , nad+ kinase , superoxide , nitric oxide , superoxide dismutase , mitochondrial respiratory chain , biology , mitochondrial ros , oxidative phosphorylation , biochemistry , chemistry , endocrinology , enzyme , genetics
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.