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(Hypertension. 2007;50:219.)
© 2007 American Heart Association, Inc.

Sixth International Workshop on Structure and Function of the Vascular System

Proinflammatory Profile Within the Grossly Normal Aged Human Aortic Wall

Mingyi Wang; Jing Zhang; Li-Qun Jiang; Gaia Spinetti; Gianfranco Pintus; Robert Monticone; Frank D. Kolodgie; Renu Virmani; Edward G. Lakatta

From the National Institute on Aging (M.W., J.Z., L-Q.J., G.S., G.P., R.M., E.G.L.), Baltimore, Md; and the Department of Cardiovascular Pathology (F.D.K., R.V.), Armed Forces Institute of Pathology, Washington, DC. Current addresses: Istituti di Ricovero e Cura a Carattere Scientifico Cardiovascolare (G.S.), Gruppo Multimedica, Milan, Italy; the Division of Biochemistry (G.P.), Department of Biomedical Sciences, School of Medicine, University of Sassari, Sassari, Italy; and the CVPath Institute, Inc (F.G.K., R.V), Gaithersburg, Md.

Correspondence to Mingyi Wang, Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Intramural Research Program, 5600 Nathan Shock Dr, Baltimore, MD 21224-6825. E-mail mingyiw{at}grc.nia.nih.gov

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.

Key Words: human • aging • arterial remodeling • Ang II • matrix metalloproteinase (MMP) • MCP-1

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