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

G. Spinetti
2004 Arteriosclerosis, Thrombosis and Vascular Biology  
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
more » ... ng (8-month) F344ϫBN 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. (Arterioscler Thromb
doi:10.1161/01.atv.0000134529.65173.08 pmid:15178559 fatcat:v77lz6sw3rcorfvq5uayfisug4