title: Vascular aging: chronic oxidative stress and impairment of redox signaling-consequences for vascular homeostasis and disease.
abstract: Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the 'free radical theory of aging' but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis.
authors.affiliation: Vascular Biology Unit, Whitaker Cardiovascular Institute, Boston University Medical Center, Boston, MA, USA. bach@bu.edu
authors.forename: Markus M
authors.initials: MM
authors.lastname: Bachschmid
authors.forename: Stefan
authors.initials: S
authors.lastname: Schildknecht
authors.forename: Reiko
authors.initials: R
authors.lastname: Matsui
authors.forename: Rebecca
authors.initials: R
authors.lastname: Zee
authors.forename: Dagmar
authors.initials: D
authors.lastname: Haeussler
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cohen
authors.forename: David
authors.initials: D
authors.lastname: Pimental
authors.forename: Bernd van der
authors.initials: Bv
authors.lastname: Loo
mesh_terms: D000375:Aging / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism* / Q000503:physiopathology; D004727:Endothelium / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008928:Mitochondria; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011453:Prostaglandins / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005609:Free Radicals; D011453:Prostaglandins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide