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


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.
Spinetti
Gaia
G
Laboratory 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
Wang
Mingyi
M
Monticone
Robert
R
Zhang
Jing
J
Zhao
Di
D
Lakatta
Edward G
EG
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects; D003433:Crosses, Genetic; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014764:Viral Proteins / Q000494:pharmacology; D037521:Virulence Factors
C414049:CCI protein, Cowpox virus; C491766:Ccl2 protein, rat; C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014764:Viral Proteins; D037521:Virulence Factors; D000804:Angiotensin II