Abstract-Percutaneous transluminal coronary angioplasty is a frequently used interventional technique to reopen arteriesthat have narrowed because of atherosclerosis. Restenosis, or renarrowing of the artery shortly after angioplasty, is a major limitation to the success of the procedure and is due mainly to smooth muscle cell accumulation in the artery wall at the site of balloon injury. In the present study, we demonstrate that the antiangiogenic sulfated oligosaccharide, PI-88, inhibits primary vascular smooth muscle cell proliferation and reduces intimal thickening 14 days after balloon angioplasty of rat and rabbit arteries. PI-88 reduced heparan sulfate content in the injured artery wall and prevented change in smooth muscle phenotype. However, the mechanism of PI-88 inhibition was not merely confined to the antiheparanase activity of this compound. PI-88 blocked extracellular signal-regulated kinase-1/2 (ERK1/2) activity within minutes of smooth muscle cell injury. It facilitated FGF-2 release from uninjured smooth muscle cells in vitro, and super-released FGF-2 after injury while inhibiting ERK1/2 activation. PI-88 inhibited the decrease in levels of FGF-2 protein in the rat artery wall within 8 minutes of injury. PI-88 also blocked injury-inducible ERK phosphorylation, without altering the clotting time in these animals. Optical biosensor studies revealed that PI-88 potently inhibited (K i 10.3 nmol/L) the interaction of FGF-2 with heparan sulfate. These findings show for the first time the capacity of this sulfated oligosaccharide to directly bind FGF-2, block cellular signaling and proliferation in vitro, and inhibit injury-induced smooth muscle cell hyperplasia in two animal models. As such, this study demonstrates a new role for PI-88 as an inhibitor of intimal thickening after balloon angioplasty. The full text of this article is available online at http://www.circresaha.org. (Circ Res. 2003;92:e70-e77.)Key Words: phosphomannopentaose sulfate Ⅲ heparanase inhibitor Ⅲ smooth muscle cells Ⅲ neointima formation Ⅲ balloon angioplasty P hosphomannopentaose sulfate (PI-88) is a recently developed synthetic polysulfated oligosaccharide that inhibits the activity of the extracellular matrix-degrading enzyme heparanase. 1 PI-88 is a 2-kDa heparan sulfate mimetic structurally distinct from heparin, a heterogenous mixture of polysaccharide chains of varying length with a molecular weights of 3 to 30 kDa. PI-88 is also structurally and functionally different from small heparin-like polyaromatic anionic-type compounds 2 and other heparan sulfate mimetics. 1 In vivo studies have shown that PI-88 is a potent inhibitor of tumor metastasis and angiogenesis. 1 Human and mammalian toxicology studies demonstrate that PI-88 is welltolerated and has low anticoagulant activity. 3 PI-88 is currently in Phase II clinical trials to assess its therapeutic potential as an anticancer drug and is administered to patients by continuous infusion or repeated injection.Percutaneous transluminal coronary angioplasty (PTCA) is common...

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Osteomas are an uncommon benign neoplasia in horses, which most frequently affect the paranasal sinuses. There are only 25 reported cases in the literature. Clinical signs typically associated with paranasal osteoma formation include nasal discharge, ocular and/or facial swelling and distortion. Historically, surgical excision under general anaesthesia has been the standard approach for the treatment of large osteomas, with standing surgery reserved for small masses. This case report describes standing removal of an extensive paranasal osteoma through a maxillary bone flap, without recurrence. Longterm follow up at 2 years confirmed a good cosmetic appearance and successful return to racing.