TY - JOUR
T1 - Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function
AU - Spinetti, Gaia
AU - Wang, Mingyi
AU - Monticone, Robert
AU - Zhang, Jing
AU - Zhao, Di
AU - Lakatta, Edward G.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
KW - Aging
KW - Aorta
KW - Chemokines
KW - Invasion
KW - Vascular smooth muscle cells
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U2 - 10.1161/01.ATV.0000134529.65173.08
DO - 10.1161/01.ATV.0000134529.65173.08
M3 - Article
C2 - 15178559
AN - SCOPUS:3943107538
SN - 1079-5642
VL - 24
SP - 1397
EP - 1402
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 8
ER -