ACCUMULATION OF FETAL FIBRONECTIN MESSENGER-RNAS AFTER BALLOON DENUDATION OF RABBIT ARTERIES

Background Fibronectin (FN), a component of the extracellular matrix, influences cellular migration and differentiation. It is a prominent c omponent of the extracellular matrix of normal arteries and is thought to play an important role in the pathogenesis of restenosis after ang ioplasty. FN exists in multiple forms that arise from a single RNA tra nscript that can be alternatively spliced. EIIIA- and EIIIB-containing FN mRNAs predominate in the embryo, whereas in the adult, most of the normal tissue FN lacks these domains. Since few data were available c oncerning pattern of expression of the different alternatively spliced forms of FN mRNA in arteries after endoluminal injury, we analyzed th e expression of EIIIA and EIIIB FN isoforms at different times after e xperimental angioplasty. Methods and Results The spatial and temporal alterations in FN expression were studied in an in vivo model of endot helial denudation in the rabbit aorta and iliac artery by a combinatio n of immunochemistry and in situ hybridization methods. Alternatively spliced forms of FN EIIIA and EIIIB were detected in the media and the adventitia of both types of vessels 24 to 48 hours after injury. Two weeks after injury, EIIIA and EIIIB mRNAs were found to accumulate wit hin the luminal layers of the neointima. The cellular form of FN prote in was not found until 2 weeks after the injury and accumulated in the inner part of the neointima. Conclusions These data demonstrate that FN upregulation is an early and long-lasting process after arterial in jury. These results suggest that the induction of the embryonic FN iso forms may be involved in the restenotic process that follows balloon d enudation of arteries.