GANGLIOSIDES AND ATHEROSCLEROSIS

The ganglioside levels in atherosclerotic lesions of human aorta are c onsiderably higher than those in unaffected areas of aorta, and athero sclerotic patients frequently have increased concentrations of serum g angliosides. The present review summarizes recent findings that sugges t the possible involvement of aortic gangliosides in platelet activati on and adhesion of platelets to the vessel wall. The effect of ganglio sides on the structure of low density lipoproteins (LDL), on the inter action of LDL with macrophages and hepatic cells and on the LDL-regula ted biosynthesis of cholesterol is also discussed. In vitro experiment s have demonstrated that a major ganglioside of the intima of atherosc lerotic aorta induces rapid adhesion, aggregation and spreading of pla telets. Moreover, gangliosides present in elevated amounts in the inte rcellular space of atherosclerotic aortic tissue modify the surface st ructure and stimulate aggregation of EDL. Ganglioside-modified LDL are readily recognized and taken up by macrophages, while preincubation o f LDL with low concentrations of gangliosides inhibits LDL binding to hepatic cells. Thus, ganglioside enrichment of LDL is likely to interf ere with LDL clearance via the hepatic cells. Thus, ganglioside enrich ment of LDL is likely to interfere with LDL clearance via the hepatic LDL receptor, and to stimulate binding of LDL to the scavenger recepto r of macrophages. It is postulated that high ganglioside levels in the aorta and serum may be an additional risk factor in atherosclerosis.