Inhibition of transforming growth factor-β restores endothelial thromboresistance in vein grafts

Vein grafts (VGs) are commonly used conduits for coronary and peripheral arterial bypass surgeries. Thrombosis is a major cause of early VG failure. Trombomodulin (TM), a key component of the anticoagulant protein C pathway, is downregulated early after VG implantation and facilitates local thrombus formation. We found that paracrine release of transforming growth factor-β1 (TGF-β1), caused by pressure-induced stretch, was a potent negative regulator of TM in rabbit VGs. Administration of a neutralizing anti-TGF-β antibody effectively prevented TM downregulation and reduced local thrombus generation without adversely affecting long-term VG remodeling. This may represent a novel strategy to improve patency in patients undergoing arterial bypass procedures.