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 respons e to injury, and the results are discordant. Moreover, the effect of a ging 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 product ion in injured rat aorta. Aorta was analysed in sham-operated rats (gr oup DO) and 14 (D14) and 28 (D28) days after injury using biochemical and immunohistochemical techniques. Uninjured aorta of old rats was mo re thickened than that of young rats; it showed a decreased number of arterial smooth muscle cells (ASMC) and was characterized by HA accumu lation in the intima and increased hyaluronidase activity. Intima-medi a wet weight was significantly increased in young rats at D14 and D28 but remained unchanged in old rats. DNA content was significantly enha nced at D14 in both young and old rats. DNA decreased slightly in youn g rats at D28 but significantly in old rats to return to control level . HA content and hyaluronidase activity in the intima-media were marke dly increased in young rats at D14 (+ 148% and + 116% respectively) bu t slightly in old rats (+ 23% and + 15% respectively). Both HA and hya luronidase activity continued to increase at D28, but remained more pr oduced in young rats. The immunohistochemical analysis showed the form ation of a thickened neointima in young rats, which was associated wit h strong expression of HA and HN. Neointima of old rats was reduced; i t also showed strong expression of HA and HN but their distributions w ere different from those observed in neointima of young rats. In concl usion, aorta of old rats showed an increased amount of HA in the intim a and elevated activity of hyaluronidase. Injury induced formation of a significant neointima in young rats but not in old rats. This was co rrelated with more HA and hyaluronidase production in injured aorta of young rats. As HA is considered to increase extracellular matrix spac e and to promote ASMC proliferation and migration, our findings sugges t that HA may be implicated in intima thickening with age and after in jury. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.