REDUCTION OF INTIMAL HYPERPLASIA BY NAROPARCIL, A 4-METHYLUMBELLIFERYL BETA-D-XYLOSIDE ANALOG, AFTER ARTERIAL INJURY IN THE HYPERCHOLESTEROLEMIC RABBIT

4-Methylumbelliferyl beta-D-xylosides (beta-D-xylosides) inhibit prote oglycan synthesis, and this is associated with reduced proliferation a nd extracellular matrix production by vascular smooth muscle cells. Th is study evaluated whether treatment with naroparcil, a beta-D-xylosid e analogue, reduced intimal hyperplasia after arterial injury in the h ypercholesterolemic rabbit. Forty-two rabbits were assigned to three g roups 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 underw ent iliac artery endothelial abrasion at day 14 and were killed at day 56. At the time of death, the angiographic minimal luminal diameter w as significantly larger in both treated groups. Morphometric analysis showed a larger luminal area in treated rabbits (groups 2 and 3) compa red with control rabbits (group 1) (0.75+/-0.54 and 0.85+/-0.61 mm(2) versus 0.32+/-0.25 mm(2), respectively; P<.05), with a decreased intim al thickness in groups 2 and 3 (average reduction of 37% and 39%, resp ectively, 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 an d a larger fractional area of smooth muscle cells. There were no diffe rences 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 naroparc il appears to preserve the arterial lumen and reduce intimal thickness after arterial injury.