Increased hyaluronan and hyaluronidase production and hyaluronan degradation in injured aorta of insulin-resistant rats

Diabetic patients have a greater incidence of restenosis, which has been sh own to be related to exaggerated intimal hyperplasia. Hyaluronan (HA) has b een shown to be closely involved in arterial smooth muscle cell proliferati on and migration, which provoke intimal hyperplasia after balloon catheter injury, Our aim was to determine the effect of fructose feeding, which prod uces certain characteristics of non-insulin-dependent diabetes tie, insulin resistance, hyperinsulinemia, and hypertriglyceridemia), on production of HA and hyaluronidase and degradation of HA in rat aorta. Treated rats recei ved fructose (25% in tap water) 12 weeks before balloon catheter injury and 14 days afterward. Fructose-fed rats had hyperinsulinemia and hypertriglyc eridemia. Injury increased intima-media wet weight (7.5%) and DNA content ( 20%) in control rats. This increase was significantly greater in fructose-f ed rats (22% for wet weight and 34% for DNA content) and was associated wit h greater HA and hyaluronidase production(123% and 41%, respectively) than in control rats (49% and 7%, respectively). Determination of HA molecular m ass showed that balloon catheter injury increased the number of HA fragment s in the aorta of control rats, Normal aorta of fructose-fed rats contained more HA fragments than that of control rats. Injury to the aorta of fructo se-fed rats increased HA fragments and induced the appearance of a very-hig h-molecular-mass (>2000 kDa) HA. In conclusion, fructose treatment, which i nduced hyperinsulinemia and hypertriglyceridemia, increased HA and hyaluron idase production and HA degradation in injured aorta. This finding suggests that HA, which has been shown to play a crucial role in proliferation and migration of arterial smooth muscle cells, may be involved in the promotion al effect of long-term fructose feeding on arterial wall reaction to injury .