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.