SorLA modulates atheroprotective properties of CLA by regulating monocyte migration
| Autor: | Peadar O'Gaora, Monica de Gaetano, William G. James, Sarah McClelland, Cathal McCarthy, Desmond J. Fitzgerald, Orina Belton |
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| Rok vydání: | 2010 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Peroxisome proliferator-activated receptor Biology Monocytes Receptors Urokinase Plasminogen Activator Mice Troglitazone Cell Movement Internal medicine medicine Animals Humans Linoleic Acids Conjugated Chromans Receptor Chemokine CCL2 chemistry.chemical_classification integumentary system Monocyte Membrane Transport Proteins food and beverages Chemotaxis Atherosclerosis Cell biology PPAR gamma Urokinase receptor Endocrinology medicine.anatomical_structure Receptors LDL chemistry LDL receptor Thiazolidinediones lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Atherosclerosis. 213:400-407 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2010.09.025 |
| Popis: | Objective: We have previously shown that CLA induces regression of pre-established atherosclerotic lesions in apoE −/− mice. CLA is a known ligand of peroxisome proliferator activated receptors (PPARs) and it is postulated that CLA mediates its atheroprotective effects through activation of PPARs. Earlier work in our group identified the monocyte/macrophage cell as the primary cellular target of CLA. In this study we identified novel genes regulated by CLA during the regression of atherosclerosis and characterised a role for one of these, SorLA. SorLA is a member of the vacuolar protein sorting 10 protein (Vps10p) domain receptor family, which has structural homology with the LDLR family. Methods and results: Expression of SorLA was identified with its Vps10p family member Sort1 by transcriptomic analysis of murine aorta following CLA-induced regression of atherosclerosis. Decreased expression of both receptors was confirmed by real-time PCR in the aorta of CLA-supplemented mice. SorLA protein expression was predominantly localised to monocyte/macrophage cells in the vasculature by immunohistochemistry. CLA and the PPAR- agonists, troglitazone, and 15-deoxy-prostaglandin (PG) J2, decreased protein and RNA expression of SorLA in THP-1 monocytes; while pre-treatment with a PPAR- antagonist established a PPAR- dependent role for CLA regulation of SorLA. CLA inhibits monocyte migration. Consistent with a role for SorLA in mediating this response, overexpression of SorLA increased migration of THP-1 monocytes to monocyte chemoattractant protein-1 with a coincident increase in UPAR expression. Conclusion: CLA may mediate its atheroprotective effects in part through reduced expression of SorLA and a resulting inhibition of monocyte migration in vitro. |
| Databáze: | OpenAIRE |
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