Effect of aging on neointima formation and hyaluronan, hyaluronidase and hyaluronectin production in injured rat aorta.

Few studies have examined the effect of aging on arterial wall response to injury, and the results are discordant. Moreover, the effect of aging on hyaluronan synthesis in injured vessels is unknown. The aim of this present study was to determine the effect of aging on neointima formation and hyaluronan (HA), hyaluronidase and hyaluronectin production in injured rat aorta. Aorta was analysed in sham-operated rats (group D0) and 14 (D14) and 28 (D28) days after injury using biochemical and immunohistochemical techniques. Uninjured aorta of old rats was more thickened than that of young rats; it showed a decreased number of arterial smooth muscle cells (ASMC) and was characterized by HA accumulation in the intima and increased hyaluronidase activity. Intima-media wet weight was significantly increased in young rats at D14 and D28 but remained unchanged in old rats. DNA content was significantly enhanced at D14 in both young and old rats. DNA decreased slightly in young rats at D28 but significantly in old rats to return to control level. HA content and hyaluronidase activity in the intima-media were markedly increased in young rats at D14 (+148% and +116% respectively) but slightly in old rats (+23% and +15% respectively). Both HA and hyaluronidase activity continued to increase at D28, but remained more produced in young rats. The immunohistochemical analysis showed the formation of a thickened neointima in young rats, which was associated with strong expression of HA and HN. Neointima of old rats was reduced; it also showed strong expression of HA and HN but their distributions were different from those observed in neointima of young rats. In conclusion, aorta of old rats showed an increased amount of HA in the intima and elevated activity of hyaluronidase. Injury induced formation of a significant neointima in young rats but not in old rats. This was correlated with more HA and hyaluronidase production in injured aorta of young rats. As HA is considered to increase extracellular matrix space and to promote ASMC proliferation and migration, our findings suggest that HA may be implicated in intima thickening with age and after injury.