Gangliosides and atherosclerosis

Abstract

The ganglioside levels in atherosclerotic lesions of human aorta are considerably higher than those in unaffected areas of aorta, and atherosclerotic patients frequently have increased concentrations of serum gangliosides. The present review summarizes recent findings that suggest the possible involvement of aortic gangliosides in platelet activation and adhesion of platelets to the vessel wall. The effect of gangliosides on the structure of low density lipoproteins (LDL), on the interaction of LDL with macrophages and hepatic cells and on the LDL-regulated biosynthesis of cholesterol is also discussed. In vitro experiments have demonstrated that a major ganglioside of the intima of atherosclerotic aorta induces rapid adhesion, aggregation and spreading of platelets. Moreover, gangliosides present in elevated amounts in the intercellular space of atherosclerotic aortic tissue modify the surface structure and stimulate aggregation of LDL. Ganglioside-modified LDL are readily recognized and taken up by macrophages, while preincubation of LDL with low concentrations of gangliosides inhibits LDL binding to hepatic cells. Thus, ganglioside enrichment of LDL is likely to interfere with LDL clearance via the hepatic cells. Thus, ganglioside enrichment of LDL is likely to interfere with LDL clearance via the hepatic LDL receptor, and to stimulate binding of LDL to the scavenger receptor of macrophages. It is postulated that high ganglioside levels in the aorta and serum may be an additional risk factor in atherosclerosis.

Myriocin slows the progression of established atherosclerotic lesions in apolipoprotein E gene knockout mice

“…In addition to cholesterol, the accumulation of sphingomyelin (SM) and glycosphingolipids (GSLs) in atherosclerotic lesions is well known (8)(9)(10). Similar to cholesterol, plasma SM and GSL levels are also correlated with atherosclerosis risk (11)(12)(13).…”

Modulation of Growth Factor Receptors in Membrane Microdomains

“…Gangliosides present in serum are known to be associated with serum lipoproteins (45), and increased levels of serum gangliosides have been found in patients with hyperlipidemia (46)(47)(48). However, there have been no studies examining a relationship between serum GM3 levels and diabetes or abdominal obesity.…”

The Possible Contribution of a General Glycosphingolipid Transporter, GM2 Activator Protein, to Atherosclerosis

“…These results indicate that ganglioside-rich LDL particles aggregate and are taken up by macrophages, consequently giving rise to fatty streaks. Furthermore, pretreatment of LDL with ganglioside inhibits LDL binding to hepatocytes 14) , suggesting that ganglioside-rich LDL may interfere with LDL clearance via the liver. Namely, ganglioside-rich LDL is presumably bound to scavenger receptors as well as oxidized LDL, but it remains to be elucidated.…”