Exogenous Ganglioside GM1 Exacerbates Atherosclerosis in apoE–/– Mice Fed a High-Fat Diet

Background: Atherosclerotic cardiovascular diseases (ASCVDs) are leading causes of mortality and disability worldwide. Endogenous monosialotetrahexosylganglioside (ganglioside GM1), a major component of cell membrane lipid rafts, plays an important role in atherogenesis. However, the specific in vivo effects of exogenous GM1 on atherosclerosis remain poorly understood. Methods: To investigate these effects, an atherosclerotic model was established using apolipoprotein E-deficient (apoE–/–) mice fed a high-fat diet (HFD) for 12 weeks. The treatment group received intravenous injections of GM1 (7.5 mg/kg) via the tail vein once every 3 days, whereas the apoE–/– HFD group received phosphate-buffered saline (PBS). Disease progression was evaluated by monitoring body and liver weights, measuring systemic lipid levels, and quantifying atherosclerotic plaque areas in the aortic arch, whole aorta, and aortic root. Results: Exogenous GM1 treatment significantly increased atherosclerotic plaque formation in the whole aorta and aortic root compared with the apoE–/– HFD group. This effect occurred without increases in total cholesterol (TCH), low-density lipoprotein-cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) levels, whereas plasma triglyceride (TG) levels were significantly reduced. Conclusions: Exogenous ganglioside GM1 exacerbated atherosclerosis in apoE–/– mice, contrasting with the previously reported atheroprotective effects of its precursor, monosialodihexosylganglioside (GM3). Although the mechanisms underlying this effect remain unclear, potentially involving direct vascular signalling or alterations in lipid raft composition, these findings support further investigation of the role of GM1 and its metabolic pathways as critical targets for further research in atherosclerosis biology.