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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1397.)
© 2004 American Heart Association, Inc.

Vascular Biology

Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function

Gaia Spinetti; Mingyi Wang; Robert Monticone; Jing Zhang; Di Zhao; Edward G. Lakatta

From the Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Md.

Correspondence to Gaia Spinetti, PhD, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr, Baltimore, MD 21224. E-mail spinettiga{at}grc.nia.nih.gov

Objective— With age, rat arterial walls thicken and vascular smooth muscle cells (VSMCs) exhibit enhanced migration and proliferation. Monocyte chemotactic protein-1 (MCP-1) affects these VSMC properties in vitro. Because arterial angiotensin II, which induces MCP-1 expression, increases with age, we hypothesized that aortic MCP-1 and its receptor CCR2 are also upregulated and affect VSMC properties.

Methods and Results— Both MCP-1 and CCR2 mRNAs and proteins increased in old (30-month) versus young (8-month) F344xBN rat aortas in vivo. Cellular MCP-1 and CCR2 staining colocalized with that of -smooth muscle actin in the thickened aortas of old rats and were expressed by early-passage VSMCs isolated from old aortas, which, relative to young VSMCs, exhibited increased invasion, and the age difference was abolished by vCCI, an inhibitor of CCR2 signaling. MCP-1 treatment of young VSMCs induced migration and increased their ability to invade a synthetic basement membrane. The MCP-1–dependent VSMC invasiveness was blocked by vCCI. After MCP-1 treatment, migration and invasion capacities of VSMCs from young aortas no longer differed from those of VSMCs isolated from older rats.

Conclusions— Arterial wall and VSMC MCP-1/CCR2 increase with aging. MCP-1 enhances VSMC migration and invasion, and thus, MCP-1/CCR2 signaling may play a role in age-associated arterial remodeling.

This study demonstrates that MCP-1 and CCR2 are increased within the thickened aortas of older rats. In early-passage VSMCs from young rats, MCP-1 increased migration and invasion, imparting to these cells the characteristics of VSMCs from older rat aorta. Thus, MCP-1/CCR2 may be implicated in age-associated vascular remodeling.

Key Words: chemokines • aging • aorta • vascular smooth muscle cells • invasion

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