PMID- 22538014 OWN - NLM STAT- MEDLINE DCOM- 20120723 LR - 20200715 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 90 IP - 21-22 DP - 2012 Jun 6 TI - Sphingomyelin synthase 2 over-expression induces expression of aortic inflammatory biomarkers and decreases circulating EPCs in ApoE KO mice. PG - 867-73 LID - 10.1016/j.lfs.2012.04.003 [doi] AB - AIMS: This study sought to assess the effect of sphingomyelin synthase 2 (SMS2) over-expression on plaque component and endothelial dysfunction in atherosclerosis. MAIN METHODS: We generated recombinant adenovirus vectors containing human SMS2 cDNA (AdV-SMS2) or control gene GFP cDNA (AdV-GFP). Both AdVs were injected (i.v.) into ApoE KO mice to establish SMS2 over-expressing and control mice models, respectively. The mice were fed a high fat diet for 30 days. We then examined their plasma lipid levels, expression levels of aortic inflammatory biomarkers critical for the plaque's stability, and numbers of peripheral endothelial progenitor cells (EPC). KEY FINDINGS: Compared with the control mice, SMS2 over-expression had significantly (1) increased aortic matrix metalloproteinase-2 (MMP-2), monocyte chemoattractant protein-1 (MCP-1), tissue factor (TF) and cyclooxygenase-2 (COX-2) mRNA levels (1.9-fold, 2.2-fold, 2.6-fold and 3.2-fold, respectively, P<0.01) and protein levels (2.2-fold, 1.9-fold, 1.9-fold and 2.1-fold, respectively, P<0.01); (2) increased MMP-2, COX-2 in situ expression in aortic root (2.6-fold and 2.3-fold, respectively, P<0.01); (3) decreased aortic COX-1 mRNA levels (65%, P<0.01) and protein levels (64%, P<0.01); and (4) decreased CD34/KDR-positive cells (33%, P<0.01), circulating angiogenic cells (CACs) (50%, P<0.05), and colony forming units (CFUs) (40%, P<0.05) in circulation. SIGNIFICANCE: SMS2 over-expression was probably associated with increased expression of aortic inflammatory biomarkers, as well as decreased numbers of CD34/KDR-positive cells, CACs and CFUs in circulation. Therefore, SMS2 over-expression might correlate with endothelial dysfunction and aggravate atherosclerotic plaque instability in ApoE KO mice. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Zhao, Ya-Rui AU - Zhao YR AD - School of Pharmacy, Fudan University, Shanghai, China. FAU - Dong, Ji-Bin AU - Dong JB FAU - Li, Yue AU - Li Y FAU - Wu, Man-Ping AU - Wu MP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120413 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Apolipoproteins E) RN - 0 (Biomarkers) RN - 0 (DNA, Complementary) RN - 0 (Membrane Proteins) RN - 0 (Nerve Tissue Proteins) RN - EC 2.7.8.- (SGMS1 protein, human) RN - EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups)) RN - EC 2.7.8.27 (Sgms2 protein, mouse) SB - IM MH - Adenoviridae/genetics MH - Animals MH - Aorta/physiopathology MH - Apolipoproteins E/*genetics MH - Atherosclerosis/genetics/*physiopathology MH - Biomarkers/metabolism MH - DNA, Complementary/genetics MH - Disease Models, Animal MH - Endothelial Cells/metabolism MH - Gene Expression Regulation MH - Genetic Vectors MH - Humans MH - Inflammation/genetics/*physiopathology MH - Male MH - Membrane Proteins/genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Nerve Tissue Proteins/genetics MH - Plaque, Atherosclerotic/genetics/*pathology MH - Stem Cells/metabolism MH - Transferases (Other Substituted Phosphate Groups)/*genetics EDAT- 2012/04/28 06:00 MHDA- 2012/07/24 06:00 CRDT- 2012/04/28 06:00 PHST- 2011/11/05 00:00 [received] PHST- 2012/02/22 00:00 [revised] PHST- 2012/04/03 00:00 [accepted] PHST- 2012/04/28 06:00 [entrez] PHST- 2012/04/28 06:00 [pubmed] PHST- 2012/07/24 06:00 [medline] AID - S0024-3205(12)00171-3 [pii] AID - 10.1016/j.lfs.2012.04.003 [doi] PST - ppublish SO - Life Sci. 2012 Jun 6;90(21-22):867-73. doi: 10.1016/j.lfs.2012.04.003. Epub 2012 Apr 13.