title: DNA Damage and Repair in Vascular Disease.
abstract: DNA damage affecting both genomic and mitochondrial DNA is present in a variety of both inherited and acquired vascular diseases. Multiple cell types show persistent DNA damage and a range of lesions. In turn, DNA damage activates a variety of DNA repair mechanisms, many of which are activated in vascular disease. Such DNA repair mechanisms either stall the cell cycle to allow repair to occur or trigger apoptosis or cell senescence to prevent propagation of damaged DNA. Recent evidence has indicated that DNA damage occurs early, is progressive, and is sufficient to impair function of cells composing the vascular wall. The consequences of persistent genomic and mitochondrial DNA damage, including inflammation, cell senescence, and apoptosis, are present in vascular disease. DNA damage can thus directly cause vascular disease, opening up new possibilities for both prevention and treatment. We review the evidence for and the causes, types, and consequences of DNA damage in vascular disease.
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; email: aku22@cam.ac.uk , mrb@mole.bio.cam.ac.uk.
authors.forename: Anna
authors.initials: A
authors.lastname: Uryga
authors.affiliation: Cardiovascular Safety, AstraZeneca, Cambridge CB4 0FZ, United Kingdom; email: kelly.gray@astrazeneca.com.
authors.forename: Kelly
authors.initials: K
authors.lastname: Gray
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; email: aku22@cam.ac.uk , mrb@mole.bio.cam.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Bennett
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D014652:Vascular Diseases / Q000235:genetics* / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial
keywords: DNA damage; DNA repair; atherosclerosis; senescence