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Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice
BACKGROUND: Sphingomyelin synthase 2 (SMS2) contributes to de novo sphingomyelin (SM) biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis. METHODS: The Adenovir...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032723/ https://www.ncbi.nlm.nih.gov/pubmed/21235823 http://dx.doi.org/10.1186/1476-511X-10-7 |
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author | Wang, Xiaogang Dong, Jibin Zhao, Yarui Li, Yue Wu, Manping |
author_facet | Wang, Xiaogang Dong, Jibin Zhao, Yarui Li, Yue Wu, Manping |
author_sort | Wang, Xiaogang |
collection | PubMed |
description | BACKGROUND: Sphingomyelin synthase 2 (SMS2) contributes to de novo sphingomyelin (SM) biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis. METHODS: The Adenovirus containing SMS2 gene was given into 10-week ApoE KO C57BL/6J mice by femoral intravenous injection. In the control group, the Adenovirus containing GFP was given. To confirm this model, we took both mRNA level examination (RT-PCR) and protein level examination (SMS activity assay). RESULT: We generated recombinant adenovirus vectors containing either human SMS2 cDNA (AdV-SMS2) or GFP cDNA (AdV-GFP). On day six after intravenous infusion of 2 × 10(11 )particle numbers into ten-week-old apoE KO mice, AdV-SMS2 treatment significantly increased liver SMS2 mRNA levels and SMS activity (by 2.7-fold, 2.3-fold, p < 0.001, respectively), compared to AdV-GFP treated mice. Moreover, plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and sphingomyelin (SM) levels were significantly increased by 39% (p < 0.05), 42% (p < 0.05), 68% (p < 0.001), and 45% (p < 0.05), respectively. Plasma high-density lipoprotein cholesterol (HDL-C), phosphatidylcholine (PC), and PC/SM ratio were decreased by 42% (p < 0.05), 18% (p < 0.05), and 45% (p < 0.05), respectively. On day 30, the atherosclerotic lesions on the aortic arch of AdV-SMS2 treated mice were increased, and the lesion areas on the whole aorta and in the aortic root were significantly increased (p < 0.001). Furthermore, the collagen content in the aorta root was significantly decreased (p < 0.01). CONCLUSIONS: Our results present direct morphological evidence for the pro-atherogenic capabilities of SMS2. SMS2 could be a potential target for treating atherosclerosis. |
format | Text |
id | pubmed-3032723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30327232011-02-03 Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice Wang, Xiaogang Dong, Jibin Zhao, Yarui Li, Yue Wu, Manping Lipids Health Dis Research BACKGROUND: Sphingomyelin synthase 2 (SMS2) contributes to de novo sphingomyelin (SM) biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis. METHODS: The Adenovirus containing SMS2 gene was given into 10-week ApoE KO C57BL/6J mice by femoral intravenous injection. In the control group, the Adenovirus containing GFP was given. To confirm this model, we took both mRNA level examination (RT-PCR) and protein level examination (SMS activity assay). RESULT: We generated recombinant adenovirus vectors containing either human SMS2 cDNA (AdV-SMS2) or GFP cDNA (AdV-GFP). On day six after intravenous infusion of 2 × 10(11 )particle numbers into ten-week-old apoE KO mice, AdV-SMS2 treatment significantly increased liver SMS2 mRNA levels and SMS activity (by 2.7-fold, 2.3-fold, p < 0.001, respectively), compared to AdV-GFP treated mice. Moreover, plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and sphingomyelin (SM) levels were significantly increased by 39% (p < 0.05), 42% (p < 0.05), 68% (p < 0.001), and 45% (p < 0.05), respectively. Plasma high-density lipoprotein cholesterol (HDL-C), phosphatidylcholine (PC), and PC/SM ratio were decreased by 42% (p < 0.05), 18% (p < 0.05), and 45% (p < 0.05), respectively. On day 30, the atherosclerotic lesions on the aortic arch of AdV-SMS2 treated mice were increased, and the lesion areas on the whole aorta and in the aortic root were significantly increased (p < 0.001). Furthermore, the collagen content in the aorta root was significantly decreased (p < 0.01). CONCLUSIONS: Our results present direct morphological evidence for the pro-atherogenic capabilities of SMS2. SMS2 could be a potential target for treating atherosclerosis. BioMed Central 2011-01-17 /pmc/articles/PMC3032723/ /pubmed/21235823 http://dx.doi.org/10.1186/1476-511X-10-7 Text en Copyright ©2011 Wang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Wang, Xiaogang Dong, Jibin Zhao, Yarui Li, Yue Wu, Manping Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice |
title | Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice |
title_full | Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice |
title_fullStr | Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice |
title_full_unstemmed | Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice |
title_short | Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice |
title_sort | adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in apoe ko mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032723/ https://www.ncbi.nlm.nih.gov/pubmed/21235823 http://dx.doi.org/10.1186/1476-511X-10-7 |
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