4-Methylumbelliferyl beta-D-
xylosides (beta-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
beta-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.