DEXTRAN SULFATE, A COMPETITIVE INHIBITOR FOR SCAVENGER RECEPTOR, PREVENTS THE PROGRESSION OF ATHEROSCLEROSIS IN WATANABE HERITABLE HYPERLIPIDEMIC RABBITS

Dextran sulfate competes with binding of modified LDL to the scavenger receptor in macrophages. To elucidate the role of dextran sulfate in the atherosclerotic process, 100 mg of dextran sulfate in drinking wat er was given to 5 Watanabe heritable hyperlipidemic (WHHL) rabbits for 12 months starting at age 4 months. During the experimental period, t here were no significant differences in plasma cholesterol levels betw een dextran sulfate-treated and untreated rabbits. After 12 months' tr eatment, accumulation of cholesterol ester in total aorta was signific antly suppressed in dextran sulfate-treated rabbits as compared with u ntreated rabbits (71.4 +/- 22.3 vs. 42.7 +/- 16.5 mg/g dry weight, P < 0.05). Furthermore, lesion area with atherosclerotic plaques in treat ed rabbits was significantly less than that in untreated rabbits (59.7 +/- 24.5 vs. 30.4 +/- 14.4%, P < 0.05). These results indicate that d extran sulfate might prevent the progression of atherosclerosis by com petitively inhibiting the binding of modified LDL to scavenger recepto rs.