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

Research output: Contribution to journalArticlepeer-review

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 α-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.

Original languageEnglish
Pages (from-to)1397-1402
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 2004

Keywords

  • Aging
  • Aorta
  • Chemokines
  • Invasion
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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