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Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1397-402. Epub 2004 Jun 3.

Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function.

Author information

  • 1Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr, Baltimore, MD 21224, USA. spinettiga@grc.nia.nih.gov

Abstract

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 alpha-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.

PMID:
15178559
[PubMed - indexed for MEDLINE]
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