title: Age-related changes in the signaling and function of vascular smooth muscle cells.
abstract: Aging is an independent risk factor for the development of atherosclerosis, a vascular abnormality that plays a significant role in the development of many cardiovascular disorders. Animal experiments have demonstrated that aging predisposes the vasculature to advanced atherosclerotic disease and vessel injury and that this predisposition is a function of age-associated changes in the vessel wall itself. Because vascular smooth muscle cells play important roles in the pathogenesis of many vascular disorders, identifying age-associated differences in the way these cells respond to extracellular clues has been an area of active research. Currently, the most remarkable differences in intracellular signaling between vascular smooth muscle cells isolated from young and old animals are related to the control of cell migration through the CamKII pathways and the accelerated transition of older vascular smooth muscle cells from the contractile to the synthetic phenotype. These differences may be due to alternative signaling pathways revealed by the inability of older cells to respond to inhibitors, such as transforming growth factor (TGF)-beta1, or to altered interactions with the extracellular matrix resulting from age-associated shifts in integrin expression or changes in the matrix composition of blood vessels. The exact role that these alterations have in explaining age-associated differences in the response of the vessel wall to injury and its increased susceptibility to developing advanced atherosclerotic lesions remains to be determined but will be guided by studies on intracellular signaling mechanisms.
authors.affiliation: Vascular Biology Unit, Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Lundberg
authors.forename: M T
authors.initials: MT
authors.lastname: Crow
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000502:physiology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology
chemical_list: D017127:Glycation End Products, Advanced; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2; D020928:Mitogen-Activated Protein Kinases