title: Role of somatic mutations in vascular disease formation.
abstract: Coronary artery disease, cerebrovascular disease, pulmonary artery hypertension and Alzheimer's disease all lead to substantial morbidity and mortality, and we currently lack effective treatments for these vascular diseases. Since the discovery, decades ago, that atherosclerotic lesions display clonal growth, atherosclerosis and other vascular diseases have been postulated to be neoplastic processes, arising through a series of critical somatic mutations. There is conflicting evidence supporting this but studies of DNA damage and mutagenesis, both genomic and mitochondrial, in atherosclerotic and vascular lesions, have yielded evidence that somatic mutations are involved in atherogenesis and vascular disease development. The roles of mitochondrial DNA damage, oxidative stress and signaling by members of the TGF-beta receptor family are implicated. With the increasing convenience and cost-effectiveness of genome sequencing, it is feasible to continue to seek specific genetic targets in the pathogenesis of these devastating diseases, with the hope of developing personalized genomic medicine in the future.
authors.affiliation: Michael E DeBakey Department of Surgery, Molecular Surgeon Research Center, Baylor College of Medicine, One Baylor Plaza, Mail Stop: BCM391, Houston, TX 77030, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Weakley
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kougias
authors.forename: Peter H
authors.initials: PH
authors.lastname: Lin
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yao
authors.forename: F Charles
authors.initials: FC
authors.lastname: Brunicardi
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Changyi
authors.initials: C
authors.lastname: Chen
mesh_terms: D004249:DNA Damage; D006801:Humans; D016296:Mutagenesis; D009154:Mutation; D018384:Oxidative Stress; D014652:Vascular Diseases / Q000235:genetics*