Comparative Studies on the Mechanisms of Action of Four Polysaccharides on Arterial Restenosis

Abstract

Percutaneous coronary interventions play a major role in the management of patients affected by coronary artery diseases. However, their efficiency is impaired by restenosis, defined as a reduction of the vessel lumen, occurring a few months after the procedure. A low-molecular-weight fraction of fucoidan, a vegetal heparin-like sulphated polysaccharide, was recently shown to greatly reduce in-stent restenosis after angioplasty in rabbits. To better understand the in vivo anti-restenotic effects of this polymer, we used fractions of fucoidan and compared to heparin and dextran of different sizes. We carried out in vitro growth inhibition experiments on vascular smooth muscle cells, performed an in vivo pharmacokinetic study, and locally delivered fluorescently-labeled polysaccharides in rabbit iliac arteries after angioplasty with a non-occlusive catheter. The results indicated that (i) preparation of well-characterized fractions from natural fucoidan is compulsory for in vitro and in vivo studies, (ii) antiproliferative activity of sulphated polysaccharides on cultured smooth muscle cells is not a major predictive factor for the reduction of restenosis in vivo and (iii) pharmacokinetic parameters and binding of low-molecular-weight fucoidan on angioplasty-induced injured vascular walls are important local and general factors controlling its mechanisms of action.

Low molecular weight (LMW) heparin inhibits injury-induced femoral artery remodeling in mouse via upregulating CD44 expression

“…Previous studies have suggested that LMW heparin could inhibit VSMC proliferation, which is the major pathologic change in occlusive disease. 13,14 CD44 is an important cell-surface specific receptor for hyaluronan. 15 There are very few studies defining the role of CD44 in the injury-induced remodeling lesions and some studies have shown controversial results.…”

Advances in Fabrication Technologies for the Development of Next-Generation Cardiovascular Stents

“…This duration was longer than that for the air−dried BSG, which confirmed the sustained release of heparin from the implant. Several polysaccharides, glycosaminoglycans, and extracellular matrix proteins have been immobilized for better endothelial cell growth, such as sulphated polysaccharides like heparin, fucoidan [130][131][132][133], chondroitin sulphate [134,135], and non−sulphated polysaccharide like hyaluronic acid [136]. Heparin is a sulfated glycosaminoglycan that is often used as an anticoagulant drug coating on metal stents to prevent thrombosis [137] and is an anti−inflammatory medication used to treat obstructive bronchopulmonary disease [138].…”

Recent advances to accelerate re-endothelialization for vascular stents

“…[27][28][29][30][31] It has been demonstrated that low-molecular-weight fucoidan (LMWF) reduces the proliferation of SMCs and consequently prevents neointimal hyperplasia in rabbit model. [32][33][34] Roux et al 35 showed an early endothelial repair for an aortic allograft model. LMWF significantly reduced intimal hyperplasia after 21 days which was associated with intimal re-endothelialization due to recruitment of bone-marrow-derived, properly, endothelial progenitor cells (EPCs).…”