title: Proinflammatory profile within the grossly normal aged human aortic wall.
abstract: Studies in animal models demonstrate that angiotensin II and its downstream signaling molecules, that is, matrix metalloproteinases and monocyte chemoattractant protein-1, increase within the diffusely thickened intima of central arteries with aging. Whether such age-related changes occur within the human arterial wall is unknown. We harvested "grossly normal thoracic aortas" from 5 young (20+/-3 years) and 5 old white males (65+/-6 years) at necropsy, after death from traumatic causes. The intimae of older samples were markedly and diffusely thickened compared with younger intimae and contained increased levels of angiotensin-converting enzyme, angiotensin II, angiotensin II receptor type 1, matrix metalloproteinases 2/9, monocyte chemoattractant protein-1, and collagen I and III proteins. In situ activities of metalloproteinases 2/9 were also significantly enhanced within old, normal aortas. The thickened intima of older aortas also contained a 5-fold increase in the embryonic form of smooth muscle myosin heavy chain-labeled cells than that of younger aortas, and these fetal-type cells were colocalized with angiotensin II protein staining. The ability of isolated smooth muscle cells to invade an artificial basement membrane in response to a monocyte chemoattractant protein-1 gradient increased with age. Furthermore, angiotensin II increased the invasive capacity of young smooth muscle cells, and this effect was reduced by a metalloproteinase inhibitor or an angiotensin II receptor blocker. Thus, in the absence of lipid infiltration, the aged human aortic wall exhibits a proinflammatory profile that renders it a fertile substrate for the development of arterial disease, for example, atherosclerosis and hypertension.
authors: National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6825, USA. mingyiw@grc.nia.nih.gov
authors: Mingyi
authors: M
authors: Wang
authors: Jing
authors: J
authors: Zhang
authors: Li-Qun
authors: LQ
authors: Jiang
authors: Gaia
authors: G
authors: Spinetti
authors: Gianfranco
authors: G
authors: Pintus
authors: Robert
authors: R
authors: Monticone
authors: Frank D
authors: FD
authors: Kolodgie
authors: Renu
authors: R
authors: Virmani
authors: Edward G
authors: EG
authors: Lakatta
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D012016:Reference Values; D012084:Renin-Angiotensin System; D017539:Tunica Intima / Q000502:physiology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009218:Myosins