Hyaluronan (HYAL-BV 5200) inhibits neo-intimal macrophage influx after balloon-catheter induced injury in the cholesterol-fed rabbit.
Hyaluronan is a glycosaminoglycan, elaborated by several cell types, and is a major constituent of the extracellular matrix. Recent studies suggest that hyaluronan influences cell migration and proliferation. At high concentrations, it has been shown to inhibit macrophage migration in vitro. We have investigated the effects of hyaluronan administration on neo-intimal lesion development following balloon catheter injury of the common carotid artery in the cholesterol-fed New Zealand White rabbit. Hyaluronan, administered as sodium hyaluronate at the time of surgery and daily until sacrifice, 2 weeks later, reduced the absolute neo-intimal response to injury by 42% (117 +/- 16 microns to 68 +/- 11 microns; 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 < 0.02). At the time of killing, serum cholesterol levels and weight gain were comparable between the groups of animals receiving a cholesterol diet (P > 0.05). In both groups mean serum cholesterol levels at the time of the balloon injury and killing were significantly greater than at entry (P < 0.001), and significantly higher than in a group receiving control chow (P < 0.001). These data suggest that the effect of hyaluronic acid on neo-intimal size may be mediated, in part, by an inhibition of monocyte/macrophage influx, and support the view that hyaluronan impairs monocyte migration.
Ferns
G A
GA
William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, UK.
Konneh
M
M
Rutherford
C
C
Woolaghan
E
E
Anggard
E E
EE
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002339:Carotid Arteries / Q000166:cytology / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006820:Hyaluronic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits
D002791:Cholesterol, Dietary; D006820:Hyaluronic Acid; D002784:Cholesterol