Incorporation and localisation of ganglioside GM3 in human intimal atherosclerotic lesions

Abstract

Immunohistochemical examination showed that sections of intimal atherosclerotic plaques contained cells and cell clusters as well as areas of extracellular matrix specifically stained with antibodies against ganglioside GM3. No immunohistochemical staining was observed in areas bordering the plaques where there was no histological evidence of atherosclerosis. To determine whether the ganglioside GM3 deposits in the intimal plaques derived directly from plasma or were synthesised by intimal cells. intimal plaque and plasma LDL were assayed for ganglioside GM3 fatty acid composition. This assay showed that more than 50% of the fatty acids of GM3 isolated from both atherosclerotic and normal intima are either minor fatty acids or those absent from LDL GM3. We conclude that the GM3 deposits present in intimal plaque arise in intimal cells and do not derive from plasma LDL.

Association between dairy intake, lipids and vascular structure and function in diabetes

“…In addition, baseline concentration of PC 34:4, PC 32:2, GM3 16:0, GM3 18:0 and total GM3 were associated with the change in CCA-IMT such that higher baseline levels were associated with greater CCA-IMT regression. GM3 accumulation has been observed in intimal atherosclerotic lesions in the carotid artery and aorta[34] and serum GM3 has been identified as a potential marker of early atherosclerosis[35]. Therefore this finding suggests that those with greater atherosclerotic burden at baseline had greater CCA-IMT regression which is consistent with our previous finding[22].…”

Suppression of vascular smooth muscle cell responses induced by TNF-α in GM3 synthase gene transfected cells

“…Many studies have demonstrated the ganglioside composition involved in the development and progression of atherosclerosis (23)(24)(25). Studies have shown that GM1 and GM2 induce VSMC proliferation through ERK1/2 activation (31).…”

“…Several studies have shown a dual function of ganglioside GD3, in both cell proliferation and inhibition of cell growth in VSMC (32,33). A number of studies have demonstrated massive and excessive accumulation of GM3 in atherosclerotic lesions (23,24). Other studies reported that exogenously-supplied GM3 inhibited DNA synthesis independently of ERK1/2 activation in VSMC (31).…”

“…Furthermore, the addition of GM3 to the culture medium reduced PDGF-induced signaling pathways in VSMC (25). Although many studies have investigated the effects of ganglioside GM3 in VSMC (23)(24)(25)31), the exact role of GM3 endogenously generated in VSMC remains unclear. In this study, the effects of GM3 synthase gene expression on TNF-· signaling in VSMC were examined.…”

“…Moreover, previous studies showed enhanced insulin sensitivity in animal models lacking the GM3 synthase gene (22). Several studies have shown the accumulation of GM3 in atherosclerotic lesions (23,24). In another study, exogenously-supplied GM3 inhibited VSMC proliferation caused by PDGF (25).…”