EXPERIMENTAL STUDY
Adventitial remodeling after angioplasty is associated with expression of tenascin mRNA by adventitial myofibroblasts
Kurt Wallner, MD*,
Behrooz G. Sharifi, PhD*,
Prediman K. Shah, MD, FACC*,
Sumiko Noguchi, MD ,
Hector DeLeon, MD, PhD and
Josiah N. Wilcox, PhD
* Atherosclerosis Research Center, Division of Cardiology, Burns and Allen Research Institute, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California,, USA
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
Manuscript received May 18, 2000;
revised manuscript received August 29, 2000,
accepted October 4, 2000.
Reprint requests and correspondence: Dr. Behrooz G. Sharifi, Cedars-Sinai Medical Center, Davis Building #1016, 8700 Beverly Boulevard, Los Angeles, California 90048 Sharifi{at}CSMC.edu
OBJECTIVES
The purpose of this study was to determine the temporospatial expression of tenascin-C (TnC) in balloon-injured rat and porcine arteries.
BACKGROUND
Recent studies suggest that cell migration, in addition to cell proliferation, is a critical component of neointima formation after vascular injury. We have previously shown that adventitial myofibroblasts synthesize growth factors that contribute to the formation of neointima after arterial injury. We have also shown that the extracellular matrix protein, TnC, regulates cell migration. Consequently, we investigated the temporospatial expression of TnC by myofibroblasts after vascular injury.
METHODS
In situ hybridization and immunohistochemistry were used to investigate the temporospatial expression of TnC in injured arteries. Northern and Western blots were used to determine the in vitro expression of TnC.
RESULTS
In situ hybridization revealed that the major site of TnC expression early after vascular injury was the adventitial myofibroblasts. Immunohistochemical staining demonstrated that TnC expression began in adventitial myofibroblasts three days after injury. Tenascin-C expression, however, did not persist in this region. Rather, it moved progressively across the vascular wall toward the luminal surface. By one week, TnC expression reached the developing neointima. In vitro, myofibroblasts did not express TnC mRNA under basal conditions. In contrast, angiotensin II and PDGF-BB, factors that have been implicated in remodeling of balloon-injured arteries, markedly upregulated TnC mRNA.
CONCLUSIONS
Tenascin-C is expressed in response to balloon injury. Tenascin-C expression begins with adventitial myofibroblasts. Over a period of 7 to 14 days, expression moves progressively across the vessel wall to the neointima. We hypothesize that adventitial myofibroblasts are actively involved in the formation of neointima and that TnC facilitates migration of these cells during adventitial remodeling.
|
Abbreviations and Acronyms
| | RCA | = right coronary artery | | SMC | = smooth muscle cell | | TnC | = tenascin-C |
|
This article has been cited by other articles:

|
 |

|
 |
 
Y. Sawada, K. Onoda, K. Imanaka-Yoshida, J. Maruyama, K. Yamamoto, T. Yoshida, and H. Shimpo
Tenascin-C synthesized in both donor grafts and recipients accelerates artery graft stenosis
Cardiovasc Res,
June 1, 2007;
74(3):
366 - 376.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Kelly, M. Melhem, J. Zhang, G. Kasting, J. Li, M. Krishnamoorthy, S. Heffelfinger, S. Rudich, P. Desai, and P. Roy-Chaudhury
Perivascular paclitaxel wraps block arteriovenous graft stenosis in a pig model
Nephrol. Dial. Transplant.,
September 1, 2006;
21(9):
2425 - 2431.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. R. Stenmark, N. Davie, M. Frid, E. Gerasimovskaya, and M. Das
Role of the Adventitia in Pulmonary Vascular Remodeling
Physiology,
April 1, 2006;
21(2):
134 - 145.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Zargham and G. Thibault
{alpha}8{beta}1 Integrin expression in the rat carotid artery: involvement in smooth muscle cell migration and neointima formation
Cardiovasc Res,
March 1, 2005;
65(4):
813 - 822.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Yamamoto, K. Onoda, Y. Sawada, K. Fujinaga, K. Imanaka-Yoshida, H. Shimpo, T. Yoshida, and I. Yada
Tenascin-C is an essential factor for neointimal hyperplasia after aortotomy in mice
Cardiovasc Res,
February 15, 2005;
65(3):
737 - 742.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Fujinaga, K. Onoda, K. Yamamoto, K. Imanaka-Yoshida, M. Takao, T. Shimono, H. Shimpo, T. Yoshida, and I. Yada
Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-c synthesis and smooth muscle cell proliferation in free artery grafts
J. Thorac. Cardiovasc. Surg.,
September 1, 2004;
128(3):
357 - 363.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. S. Lee and R. R. Makkar
Stem-Cell Transplantation in Myocardial Infarction: A Status Report
Ann Intern Med,
May 4, 2004;
140(9):
729 - 737.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Bauriedel, A. Jabs, D. Skowasch, R. Hutter, J. J. Badimon, V. Fuster, U. Welsch, and B. Luderitz
Dendritic cells in neointima formation after rat carotid balloon injury: coordinated expression withanti-apoptotic Bcl-2 and HSP47 in arterial repair
J. Am. Coll. Cardiol.,
September 3, 2003;
42(5):
930 - 938.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Qin, Z. Zeng, J. Zheng, P. K. Shah, S. M. Schwartz, L. D. Adams, and B. G. Sharifi
Suppression Subtractive Hybridization Identifies Distinctive Expression Markers for Coronary and Internal Mammary Arteries
Arterioscler. Thromb. Vasc. Biol.,
March 1, 2003;
23(3):
425 - 433.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|