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(Circulation Research. 1995;77:919.)
© 1995 American Heart Association, Inc.

Articles

Reduction of Intimal Hyperplasia by Naroparcil, a 4-Methylumbelliferyl ß-D-Xyloside Analogue, After Arterial Injury in the Hypercholesterolemic Rabbit

Philippe Gabriel Steg, Marianne Ziol, Ouafae Tahlil, Claude Robert, Philippe Masson, Didier Pruneau, Patrick Bruneval, Pierre Bélichard

From the Unité Physiopathologie du Coeur et des Artères (P.G.S., O.T.), Faculté Xavier Bichat, Paris, France; Laboratoires Fournier-Dijon (C.R., D.P., P.M., P. Bélichard), Dijon, France; and INSERM U28, Pathologie Rénale et Vasculaire (M.Z., P. Bruneval), Hôpital Broussais, Paris, France.

Correspondence to Philippe Gabriel Steg, MD, Service de Cardiologie, Hôpital Bichat, 46 rue H. Huchard, 75018 Paris, France.

Abstract 4-Methylumbelliferyl ß-D-xylosides (ß-D-xylosides) inhibit proteoglycan synthesis, and this is associated with reduced proliferation and extracellular matrix production by vascular smooth muscle cells. This study evaluated whether treatment with naroparcil, a ß-D-xyloside analogue, reduced intimal hyperplasia after arterial injury in the hypercholesterolemic rabbit. Forty-two rabbits were assigned to three groups that received either a 1% cholesterol-enriched diet (group 1, n=15) or the same diet with added 100 mg · kg^-1 naroparcil (group 2, n=15) or 300 mg · kg^-1 naroparcil (group 3, n=12). All animals underwent iliac artery endothelial abrasion at day 14 and were killed at day 56. At the time of death, the angiographic minimal luminal diameter was significantly larger in both treated groups. Morphometric analysis showed a larger luminal area in treated rabbits (groups 2 and 3) compared with control rabbits (group 1) (0.75±0.54 and 0.85±0.61 mm² versus 0.32±0.25 mm², respectively; P<.05), with a decreased intimal thickness in groups 2 and 3 (average reduction of 37% and 39%, respectively, compared with group 1; P<.05) but without changes in medial area. Total vessel area was comparable among all groups. In the media, immunohistochemistry suggested reduced infiltration by macrophages and a larger fractional area of smooth muscle cells. There were no differences in plasma or arterial wall cholesterol content between groups. Plasma levels of glycosaminoglycans and dermatan sulfate content were increased only in group 3. In this model, oral treatment with naroparcil appears to preserve the arterial lumen and reduce intimal thickness after arterial injury.

Key Words: angioplasty • restenosis • arterial injury • glycosaminoglycans • proteoglycans

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