Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice.
The apolipoprotein E gene knockout (apoE-/-) mouse develops atherosclerosis that shares many features of human atherosclerosis. Increased levels of glycosphingolipid (GSL) have been reported in human atherosclerotic lesions; however, GSL levels have not been studied in the apoE-/- mouse. Here we use...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2002
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| _version_ | 1826283949824933888 |
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| author | Garner, B Priestman, D Stocker, R Harvey, D Butters, T Platt, F |
| author_facet | Garner, B Priestman, D Stocker, R Harvey, D Butters, T Platt, F |
| author_sort | Garner, B |
| collection | OXFORD |
| description | The apolipoprotein E gene knockout (apoE-/-) mouse develops atherosclerosis that shares many features of human atherosclerosis. Increased levels of glycosphingolipid (GSL) have been reported in human atherosclerotic lesions; however, GSL levels have not been studied in the apoE-/- mouse. Here we used HPLC methods to analyze serum and aortic GSL levels in apoE-/- and C57BL/6J control mice. The concentrations of glucosyl ceramide (GlcCer), lactosyl ceramide (LacCer), GalNAcbeta1-4Galbeta1-4Glc-Cer (GA2), and ceramide trihexoside (CTH) were increased by approximately 7-fold in the apoE-/- mouse serum compared with controls. The major serum ganglioside, N-glycolyl GalNAcbeta1-4[NeuNAcalpha2-3]Galbeta1-4Glc-Cer (N-glycolyl GM2), was increased in concentration by approximately 3-fold. A redistribution of GSLs from HDL to VLDL populations was also observed in the apoE-/- mice. These changes were accompanied by an increase in the levels of GSLs in the aortic sinus and arch of the apoE-/- mice. The spectrum of gangliosides present in the aortic tissues was more complex than that found in the lipoproteins, with the latter represented almost entirely by N-glycolyl GM2 and the former comprised of NeuNAcalpha2-3Galbeta1-4Glc-Cer (GM3), GM2, N-glycolyl GM2, GM1, GD3, and GD1a. In conclusion, neutral GSL and ganglioside levels were increased in the serum and aortae of apoE-/- mice compared with controls, and this was associated with a preferential redistribution of GSL to the proatherogenic lipoprotein populations. The apoE-/- mouse therefore represents a useful model to study the potential role of GSL metabolism in atherogenesis. |
| first_indexed | 2024-03-07T01:06:31Z |
| format | Journal article |
| id | oxford-uuid:8b82a701-4a38-41b6-9100-f41e907d0655 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:06:31Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:8b82a701-4a38-41b6-9100-f41e907d06552022-03-26T22:38:45ZIncreased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8b82a701-4a38-41b6-9100-f41e907d0655EnglishSymplectic Elements at Oxford2002Garner, BPriestman, DStocker, RHarvey, DButters, TPlatt, FThe apolipoprotein E gene knockout (apoE-/-) mouse develops atherosclerosis that shares many features of human atherosclerosis. Increased levels of glycosphingolipid (GSL) have been reported in human atherosclerotic lesions; however, GSL levels have not been studied in the apoE-/- mouse. Here we used HPLC methods to analyze serum and aortic GSL levels in apoE-/- and C57BL/6J control mice. The concentrations of glucosyl ceramide (GlcCer), lactosyl ceramide (LacCer), GalNAcbeta1-4Galbeta1-4Glc-Cer (GA2), and ceramide trihexoside (CTH) were increased by approximately 7-fold in the apoE-/- mouse serum compared with controls. The major serum ganglioside, N-glycolyl GalNAcbeta1-4[NeuNAcalpha2-3]Galbeta1-4Glc-Cer (N-glycolyl GM2), was increased in concentration by approximately 3-fold. A redistribution of GSLs from HDL to VLDL populations was also observed in the apoE-/- mice. These changes were accompanied by an increase in the levels of GSLs in the aortic sinus and arch of the apoE-/- mice. The spectrum of gangliosides present in the aortic tissues was more complex than that found in the lipoproteins, with the latter represented almost entirely by N-glycolyl GM2 and the former comprised of NeuNAcalpha2-3Galbeta1-4Glc-Cer (GM3), GM2, N-glycolyl GM2, GM1, GD3, and GD1a. In conclusion, neutral GSL and ganglioside levels were increased in the serum and aortae of apoE-/- mice compared with controls, and this was associated with a preferential redistribution of GSL to the proatherogenic lipoprotein populations. The apoE-/- mouse therefore represents a useful model to study the potential role of GSL metabolism in atherogenesis. |
| spellingShingle | Garner, B Priestman, D Stocker, R Harvey, D Butters, T Platt, F Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. |
| title | Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. |
| title_full | Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. |
| title_fullStr | Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. |
| title_full_unstemmed | Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. |
| title_short | Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. |
| title_sort | increased glycosphingolipid levels in serum and aortae of apolipoprotein e gene knockout mice |
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