Clinical and experimental approaches to the prevention of atherosclerosis by immunological regulations

To evaluate the involvement of the complement system in atherogenesis, we investigated the effect of camostat mesilate (CM), C1r, and C1 esterase inhibitor on cholesterol-induced atherosclerosis in rabbits. We also examined the effect of sodium dextran sulfate (DS, molecular weight: 7000), which is reported to be effective in preventing arteriosclerotic diseases and in inhibiting cholesterol-induced atherosclerosis in experimental animals, on complement activation in vitro and in vivo. The administration of CM reduced the formation of atherosclerotic lesions in cholesterol-fed rabbits. DS inhibited complement pathway in vitro, and the administration of DS reduced the C3a level in subjects. These results suggest that complement activation may possibly be involved in the atherosclerotic process.