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).