HYALURONAN (HYAL-BV-5200) INHIBITS NEOINTIMAL MACROPHAGE INFLUX AFTERBALLOON-CATHETER INDUCED INJURY IN THE CHOLESTEROL-FED RABBIT

Hyaluronan is a glycosaminoglycan, elaborated by several cell types, a nd is a major constituent of the extracellular matrix. Recent studies suggest that hyaluronan influences cell migration and proliferation. A t high concentrations, it has been shown to inhibit macrophage migrati on in vitro. We have investigated the effects of hyaluronan administra tion on neo-intimal lesion development following balloon catheter inju ry of the common carotid artery in the cholesterol-fed New Zealand Whi te rabbit. Hyaluronan, administered as sodium hyaluronate at the time of surgery and daily until sacrifice, 2 weeks later, reduced the absol ute neo-intimal response to injury by 42% (117 +/- 16 mu m to 68 +/- 1 1 mu m; P < 0.05), and the intima-media ratio by 35% (0.91 +/- 0.10 to 0.59 +/- 0.11; P < 0.05). This was associated with a 62% reduction in intimal macrophage content (8.63 +/- 1.85% to 3.25 +/- 1.05%; P < 0.0 2). At the time of killing, serum cholesterol levels and weight gain w ere comparable between the groups of animals receiving a cholesterol d iet (P > 0.05). In both groups mean serum cholesterol levels at the ti me of the balloon injury and killing were significantly greater than a t entry (P < 0.001), and significantly higher than in a group receivin g control chow (P < 0.001). These data suggest that the effect of hyal uronic acid on neo-intimal size may be mediated, in part, by an inhibi tion of monocyte/macrophage influx, and support the view that hyaluron an impairs monocyte migration.