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| Status |
Public on Jan 10, 2015 |
| Title |
LDLR-/- mice aorte: Control vs DHA |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The omega-3 fatty acid docosahexaenoic acid (DHA) has potent anti-atherogenic properties but its mechanisms of action at the vascular level remain poorly explored. Knowing the broad range of molecular targets of omega-3 fatty acids, microarray analysis was used to open-mindedly evaluate the effects of DHA on aorta gene expression in LDLR-/- mice and better understand its local anti-atherogenic action . Mice were fed an atherogenic diet and received daily oral gavages with oils rich in oleic acid or DHA. Bioinformatics analysis of microarray data first identified inflammation and innate immunity as processes the most affected by DHA supplementation within aorta. More precisely, several down-regulated genes were associated with the inflammatory functions of macrophages (e.g. CCL5, CCR7), cell movement (e.g. ICAM-2, SELP, PECAM-1), and the major histocompatibility complex (e.g. HLA-DQA1, HLA-DRB1). Interestingly, the expression of several genes were identified as specifc biomarkers of macrophage polarization and their changes suggested a preferential orientation towards a M2 reparative phenotype. This observation was supported by the upstream regulator analysis highlighting the involvment of three main regulators of macrophage polarization, namely PPARγ (z-score=2.367, p=1.50x10-13), INFγ (z-score=-2.797, p=2.81x10-14) and NFκB (z-score=2.360, p=6.32x10-9). Moreover, immunohistological analysis of aortic root revealed an increased abundance of Arg1 (+111%, p=0.01), a specific biomarker of M2 macrophage.The present study showed for the first time that DHA supplementation during atherogenesis is associated with protective modulation of inflammation and innate immunity pathways within aorta putatively through the orientation of plaque macrophages towards a M2 reparative phenotype.
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| Overall design |
Mice (LDLR-/-) Aorta samples. 2 groups: Control (K), DHA (C). Biological replicates=8. Dye switch.
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| Contributor(s) |
Gladine C, Zmojdzian M, Joumard-Cubizolles L, Verny M, Comte B, Mazur A |
| Citation(s) |
25134659 |
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| Submission date |
Jul 22, 2014 |
| Last update date |
Jun 21, 2019 |
| Contact name |
Cécile Gladine |
| E-mail(s) |
[email protected]
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| Phone |
+33 4 73 62 42 30
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| Organization name |
INRA
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| Department |
Human Nutrition
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| Street address |
Centra INRA de Clermont-Ferrand/Theix
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| City |
Saint-Genès-Champanelle |
| ZIP/Postal code |
63122 |
| Country |
France |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA255891 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE59661_RAW.tar |
33.4 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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