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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

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