Adventitial remodeling after angioplasty is associated with expression of tenascin mRNA by adventitial myofibroblasts

OBJECTIVES The purpose of this study was to determine the temporospatial ex pression 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 vascula r injury. We have previously shown that adventitial myofibroblasts synthesi ze growth factors that contribute to the formation of neointima after arter ial 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 investi gate 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 expressio n early after vascular injury was the adventitial myofibroblasts. Immunohis tochemical staining demonstrated that TnC expression began in adventitial m yofibroblasts three days after injury. Tenascin-C expression, however, did not persist in this region. Rather, it moved progressively across the vascu lar wall toward the luminal surface. By one week, TnC expression reached th e developing neointima. In vitro, myofibroblasts did not express TnC mRNA u nder basal conditions. In contrast, angiotensin II and PDGF-BB, factors tha t 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 neoi ntima. We hypothesize that adventitial myofibroblasts are actively involved in the formation of neointima and that TnC facilitates migration of these cells during adventitial remodeling. (C) 2001 by the American College of Ca rdiology.