title: Inhibition of anastomotic intimal hyperplasia by a synthetic nonsulphated heparin-mimicking compound.
abstract: Despite extensive research in the design of endovascular catheters and advanced surgical techniques, stenosis recurs in a large percentage of patients undergoing angioplasty or anastomosis. Hence, neointimal hyperplasia, caused by migration and proliferation of vascular smooth muscle cells (SMC), remains a significant limitation to the relief of obstructive-occlusive vascular disease. It has been previously demonstrated that heparin displaces active basic fibroblast growth factor (bFGF) from the lumenal surface of blood vessels. Sequestration of the displaced bFGF by injured areas of the vessel wall is inhibited in the presence of a synthetic nonsulphated heparin-mimicking polyanionic compound (RG-13577). This compound also induces a phenotype transformation of coronary SMC into a metabolically active hypertropic status that could promote repair processes after balloon angioplasty while inhibiting cell proliferation. In this paper, the result of a continuous administration of compound RG-13577 both in the rat carotid catheter injury model and in a newly developed rat model of surgical arterial vascular injury (anastomosis) is reported: it causes a profound inhibition of intimal hyperplasia in both models. A combined treatment with heparin/heparan sulphate mimetics and halofuginone, a potent inhibitor of collagen synthesis, extracellular matrix deposition and SMC proliferation, is expected to inhibit restenosis through inhibition of both signals/activities induced by soluble molecules (ie, heparin-binding growth factors) and components of the extracellular matrix (ie, type I collagen).
authors: Departments of Thoracic and Cardiovascular Surgery.
authors: Yaron
authors: Y
authors: Shargal
authors: Nicola
authors: N
authors: Viola
authors: Arnon
authors: A
authors: Nagler
authors: Gideon
authors: G
authors: Merin
authors: Annete
authors: A
authors: Schmidt
authors: Erick
authors: E
authors: Buddecke
authors: Shmuel A
authors: SA
authors: Ben-Sasson
authors: Israel
authors: I
authors: Vlodavsky