Published Online
on April 23, 2007

A more recent version of this article appeared on July 1, 2007

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Submitted on February 20, 2007
Revised on March 7, 2007

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; and 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.

^* To whom correspondence should be addressed. E-mail: mingyiw{at}grc.nia.nih.gov.

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.

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

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