Compositions and methods for treating and preventing neointimal stenosis

摘要

Methods for treating or preventing neointima stenosis are disclosed. The methods generally involve the use of a TGFβ inhibitor, a SMAD2 inhibitor, an FGF Receptor agonist, a Let-7 agonist, or a combination thereof, to inhibit endothelial-to-mesenchymal transition (Endo-MT) of vascular endothelial cells into smooth muscle cells (SMC) at sites of endothelial damage. The disclosed methods can therefore be used to prevent or inhibit neointimal stenosis or restenosis, e.g., after angioplasty, vascular graft, or stent. Also disclosed are methods for increasing the patency of biodegradable, synthetic vascular grafts using a composition that inhibits Endo-MT. A cell-free tissue engineered vascular graft (TEVG) produced by this method is also disclosed.

主权项

1. A method for enhancing repair or regeneration of endothelial tissue while not promoting conversion of endothelial cells into smooth muscle cells in a subject in need thereof, comprising administering to the subject immediately before, at the time of or after implantation of a vascular scaffold, stent or graft, a pharmaceutical composition comprising an effective amount of a TGFβ inhibitor, a SMAD2 inhibitor, an FGF Receptor agonist, a Let-7 agonist, or a combination thereof to promote endothelial cell growth but not smooth muscle cell proliferation.