Vascular repair processes mediated by transforming growth factor-β

Summary

Objectives. The goal of this study was to determine the role of transforming growth factor-β (TGF-β) family members in arterial repair processes related to vascular injury. Background. TGF-β plays important roles in many tissues including calcifying tissues and blood vessels. The family members of TGF-β1, -β2, and -β3 have overlapping functions and signal via the same receptor complex. To examine the role of the TGF-β in vascular remodeling and intimal hyperplasia we disrupted this signaling pathway using recombinant soluble TGF-β receptor II (TGF-βR:Fc). Methods. The balloon catheter injury model of the rat carotid artery was used and TGF-βR:Fc was injected every other day for a period of two weeks after which the vessels were harvested for analysis by histology, morphometry, and Northern blotting. Results. In situ hybridization showed TGF-β receptor II expression in smooth muscle cells (SMC) of the injured vessel wall while the same cells also revealed abundant expression of all three TGF-β ligands. Injection of TGF-βR:Fc localized to the adventitia and developing neointima in the injured carotid artery, causing a reduction in intimal lesion formation (65%) and an increase in lumen area (88%). The increase in lumen area was largely due to inhibition of negative remodeling which coincided with reduced adventitial fibrosis and collagen synthesis. Four days after inury, TGF-βR:Fc treatment almost completely inhibited the induction of smooth muscle α-actin expression in adventitial cells. Conclusions. These results identify TGF-β isoforms as the major mediators of adventitial fibrosis and negative remodeling after arterial injury, which is a major cause for restenosis following angioplasty.