| First Author | Ma Y | Year | 2008 |
| Journal | PLoS One | Volume | 3 |
| Issue | 6 | Pages | e2503 |
| PubMed ID | 18560564 | Mgi Jnum | J:137210 |
| Mgi Id | MGI:3798335 | Doi | 10.1371/journal.pone.0002503 |
| Citation | Ma Y, et al. (2008) Altered gene expression in early atherosclerosis is blocked by low level apolipoprotein E. PLoS One 3(6):e2503 |
| abstractText | BACKGROUND: Mice deficient in apolipoprotein E (apoE(-/-)) develop atherosclerosis. The possible linkage between expression of adhesion molecules/cofactors and atherosclerosis was probed at the level of mRNA and protein expression. The hypothesis of a linkage between changes of adhesion molecules/cofactors and atherosclerosis was tested further by suppression of aortic lesion formation in apoE(-/-) mice by expression of very low levels of transgenic apolipoprotein E. METHODOLOGY/PRINCIPAL FINDINGS: We show that at 8.5 months of age, the apoE(-/-) mice display elevated expression of mRNA for LFA-1, MAC-1, VCAM-1, ICAM-1, and for CD44, as well as MCP-1, cathepsin B, and COX-2 (but not that for eNOS) in atherosclerotic aortic arches. At earlier age, (10-13 week old) apoE(-/-) mice already display elevated expression of mRNA of CD44, LFA-1, MAC-1, VCAM-1, ICAM-1, cathepsin, and of COX-2 in lesioned aortic arches. Expressing very low levels of transgenic apolipoprotein E suppresses both aortic lesions and the expression of mRNA of LFA-1, VCAM-1, MCP-1, cathepsin B, and of ICAM-1 in ApoE(-/-) mice. We tested at the level of protein, the observations obtained for mRNA expression. CD11a (a component of LFA-1), VCAM-1 and cathepsin B expression was found to be elevated in apoE(-/-) aortas at 8-9 months; low level expression of transgenic apolipoprotein E rectifies these changes. CONCLUSIONS/SIGNIFICANCE: Atherosclerotic lesions in apoE(-/-) mice are detected as early as 4 weeks of age. Expression of low levels of apoE is shown to be both atheroprotective and to suppress these changes in key adhesion and inflammatory molecules observed in early atherosclerotic lesions. |
