![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
TA McCaffrey and DJ Falcone
Department of Medicine, Cornell University Medical College, New York, New York 10021.
Previous studies have indicated that aged animals show an increased intimal hyperplasia after arterial injury. The present studies examined the hypothesis that the increased serum-free proliferation of aged smooth muscle cells (SMC), in vitro, was due to a loss of an antiproliferative signal, such as transforming growth factor-beta 1 (TGF-beta 1). Northern blot analysis of the mRNA derived from old (> 19 mo) or young (3-4 mo) rat aortic SMC indicated that both groups had an equivalent level of the 2.5 kB TGF-beta 1 message. Metabolic labeling with 35S-methionine and immunoprecipitation for TGF-beta 1 confirmed the de novo synthesis of TGF-beta 1 in rat SMC. Old and young SMC supernatants showed equal levels of active or latent (acid-activated) TGF-beta activity. Despite the similarities in the production of TGF- beta 1, old SMC were refractory to inhibition by TGF-beta 1, whereas young SMC were markedly inhibited (80%) by low levels of TGF-beta 1 (IC50 < 5 pg/ml). Binding studies at 4 degrees C indicated that old SMC exhibited reduced binding capacity for 125I-TGF-beta 1. Cross-linking studies confirmed that old SMC showed reduced binding of 125I-TGF-beta 1 to membrane sites corresponding to the high molecular weight type III receptor, as well as the 85-kDa type II and 65-kDa type I receptor. However, at 37 degrees C, old SMC degraded 125I-TGF-beta 1 more rapidly than young SMC. Combined, this data suggests that SMC derived from older animals are capable of normal production of TGF-beta 1 but fail to respond to the autocrine growth inhibitory effects of this agent, thereby leading to enhanced proliferation.
This article has been cited by other articles:
|
|
 |
|
  C.-J. Liang, H. E. Ives, C.-M. Yang, and Y.-H. Ma 20-HETE inhibits the proliferation of vascular smooth muscle cells via transforming growth factor- J. Lipid Res., January 1, 2008; 49(1): 66 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Spinetti, M. Wang, R. Monticone, J. Zhang, D. Zhao, and E. G. Lakatta Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1397 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Khanna Concerted effect of transforming growth factor-{beta}, cyclin inhibitor p21, and c-myc on smooth muscle cell proliferation Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1133 - H1140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sadoun and M. J. Reed Impaired Angiogenesis in Aging Is Associated with Alterations in Vessel Density, Matrix Composition, Inflammatory Response, and Growth Factor Expression J. Histochem. Cytochem., September 1, 2003; 51(9): 1119 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hao, G. Gabbiani, and M.-L. Bochaton-Piallat Arterial Smooth Muscle Cell Heterogeneity: Implications for Atherosclerosis and Restenosis Development Arterioscler. Thromb. Vasc. Biol., September 1, 2003; 23(9): 1510 - 1520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. G. Lakatta Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part III: Cellular and Molecular Clues to Heart and Arterial Aging Circulation, January 28, 2003; 107(3): 490 - 497. [Full Text] [PDF]
|
|
|
|
 |
|
 B.-S. Lee and R. A. Nowak Human Leiomyoma Smooth Muscle Cells Show Increased Expression of Transforming Growth Factor-{beta}3 (TGF{beta}3) and Altered Responses to the Antiproliferative Effects of TGF{beta} J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 913 - 920. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Rivard, N. Principe, and V. Andres Age-dependent increase in c-fos activity and cyclin A expression in vascular smooth muscle cells: A potential link between aging, smooth muscle cell proliferation and atherosclerosis Cardiovasc Res, March 1, 2000; 45(4): 1026 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Bray, B. Du, V. M. Mejia, S. C. Hao, E. Deutsch, C. Fu, R. C. Wilson, H. Hanauske-Abel, and T. A. McCaffrey Glucocorticoid Resistance Caused by Reduced Expression of the Glucocorticoid Receptor in Cells From Human Vascular Lesions Arterioscler. Thromb. Vasc. Biol., May 1, 1999; 19(5): 1180 - 1189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Li, J. Froehlich, Z. S. Galis, and E. G. Lakatta Increased Expression of Matrix Metalloproteinase-2 in the Thickened Intima of Aged Rats Hypertension, January 1, 1999; 33(1): 116 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Du, C. Fu, K. C. Kent, H. Bush Jr., A. H. Schulick, K. Kreiger, T. Collins, and T. A. McCaffrey Elevated Egr-1 in Human Atherosclerotic Cells Transcriptionally Represses the Transforming Growth Factor-beta Type II Receptor J. Biol. Chem., December 8, 2000; 275(50): 39039 - 39047. [Abstract] [Full Text] [PDF]
|
|
