Role of Latent TGF-β1 Binding Protein in Vascular Remodeling

Abstract

Transforming growth factor-β (TGF-β) is secreted as a latent, high molecular weight complex, which is composed of TGF-β, a latency associated peptide (LAP) and a latent TGF-β binding protein (LTBP). In this study, we report on the role of LTBP in vascular remodeling. 0.01-5 ng/ml of LTBP stimulated the migration activities of cultured rat arterial smooth muscle cells (SMC) about 4-7 fold compared with control in vitro. The maximal activity of SMC migration by LTBP was 75% of that by 10 ng/ml of PDGF-BB. A checker board analysis showed that the migration by LTBP was chemotactic, not chemokinetic. By cross-linking experiment, LTBP associated with 80-120 kd cell surface protein of SMC, suggesting that a part of LTBP can bind with SMC. Furthermore, LTBP was more strongly expressed in the intimal layer than in the medial layer of BCI artery. These results suggest that LTBP plays an importantrole in the initial stage of arterial intimal thickening through the acceleration of SMC migration from the medial to intimal layer and is one of the essential factors influencing vascular remodeling.