Published online before print June 3, 2004, doi: 10.1161/01.ATV.0000134529.65173.08
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2004 American Heart Association, Inc.
Vascular Biology |
Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function
From the Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Md.
Correspondence to Gaia Spinetti, PhD, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr, Baltimore, MD 21224. E-mail spinettiga{at}grc.nia.nih.gov
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 
-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.
This study demonstrates that MCP-1 and CCR2 are increased within the thickened aortas of older rats. In early-passage VSMCs from young rats, MCP-1 increased migration and invasion, imparting to these cells the characteristics of VSMCs from older rat aorta. Thus, MCP-1/CCR2 may be implicated in age-associated vascular remodeling.
Key Words: chemokines • aging • aorta • vascular smooth muscle cells • invasion
This article has been cited by other articles:
 |
|
 |
|
  G. Spinetti, N. Kraenkel, C. Emanueli, and P. Madeddu Diabetes and vessel wall remodelling: from mechanistic insights to regenerative therapies Cardiovasc Res, May 1, 2008; 78(2): 265 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Burt, G. Salvidio, E. Tarabra, F. Barutta, S. Pinach, P. Dentelli, G. Camussi, P. C. Perin, and G. Gruden The Monocyte Chemoattractant Protein-1/Cognate CC Chemokine Receptor 2 System Affects Cell Motility in Cultured Human Podocytes Am. J. Pathol., December 1, 2007; 171(6): 1789 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Miller, W. C. Watson, K. A. Kerr, C. A. Labarrere, N. X. Chen, M. A. Deeg, and J. L. Unthank Development of progressive aortic vasculopathy in a rat model of aging Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2634 - H2643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Kundumani-Sridharan, D. Wang, M. Karpurapu, Z. Liu, C. Zhang, N. Dronadula, and G. N. Rao Suppression of Activation of Signal Transducer and Activator of Transcription-5B Signaling in the Vessel Wall Reduces Balloon Injury-Induced Neointima Formation Am. J. Pathol., October 1, 2007; 171(4): 1381 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wang, J. Zhang, L.-Q. Jiang, G. Spinetti, G. Pintus, R. Monticone, F. D. Kolodgie, R. Virmani, and E. G. Lakatta Proinflammatory Profile Within the Grossly Normal Aged Human Aortic Wall Hypertension, July 1, 2007; 50(1): 219 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. N. Mitchell and P. Libby Vascular Remodeling in Transplant Vasculopathy Circ. Res., April 13, 2007; 100(7): 967 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wang, Z. Liu, Q. Li, M. Karpurapu, V. Kundumani-Sridharan, H. Cao, N. Dronadula, F. Rizvi, A. K. Bajpai, C. Zhang, et al. An Essential Role for gp130 in Neointima Formation Following Arterial Injury Circ. Res., March 30, 2007; 100(6): 807 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ma, Q. Wang, T. Fei, J.-D. J. Han, and Y.-G. Chen MCP-1 mediates TGF-{beta}-induced angiogenesis by stimulating vascular smooth muscle cell migration Blood, February 1, 2007; 109(3): 987 - 994. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wang, D. Zhao, G. Spinetti, J. Zhang, L.-Q. Jiang, G. Pintus, R. Monticone, and E. G. Lakatta Matrix Metalloproteinase 2 Activation of Transforming Growth Factor-{beta}1 (TGF-{beta}1) and TGF-{beta}1-Type II Receptor Signaling Within the Aged Arterial Wall Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1503 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wang, J. Zhang, G. Spinetti, L.-Q. Jiang, R. Monticone, D. Zhao, L. Cheng, M. Krawczyk, M. Talan, G. Pintus, et al. Angiotensin II Activates Matrix Metalloproteinase Type II and Mimics Age-Associated Carotid Arterial Remodeling in Young Rats Am. J. Pathol., November 1, 2005; 167(5): 1429 - 1442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Najjar, A. Scuteri, and E. G. Lakatta Arterial Aging: Is It an Immutable Cardiovascular Risk Factor? Hypertension, September 1, 2005; 46(3): 454 - 462. [Abstract] [Full Text] [PDF]
|
|