title: Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function.
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.
  
  
  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.
authors.affiliation: 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
authors.forename: Gaia
authors.initials: G
authors.lastname: Spinetti
authors.forename: Mingyi
authors.initials: M
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Monticone
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
mesh_terms: 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
chemical_list: 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