Biosynthesis of proresolving lipid mediators by vascular cells and tissues
| Autor: | Sevan Komshian, Giorgio Mottola, Mian Chen, Matthew Spite, Anuran Chatterjee, Brian E. Sansbury, Bian Wu, Michael S. Conte |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Vascular smooth muscle Docosahexaenoic Acids Myocytes Smooth Muscle Biology Biochemistry Antibodies Receptors G-Protein-Coupled 03 medical and health sciences chemistry.chemical_compound Paracrine signalling Leukocytes Genetics Humans Receptors Lipoxin Autocrine signalling Receptor Molecular Biology Cells Cultured Inflammation Arachidonate 5-Lipoxygenase Molecular Structure Research Endothelial Cells Lipid signaling Lipid Metabolism Receptors Formyl Peptide Cell biology GPR32 Protein Transport 030104 developmental biology Gene Expression Regulation chemistry Cytokines Autacoid Resolvin Biotechnology |
| Zdroj: | The FASEB Journal. 31:3393-3402 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201700082r |
| Popis: | Recent evidence suggests that specialized proresolving lipid mediators (SPMs) generated from docosahexaenoic acid (DHA) can modulate the vascular injury response. However, cellular sources for these autacoids within the vessel wall remain unclear. Here, we investigated whether isolated vascular cells and tissues can produce SPMs and assessed expression and subcellular localization of the key SPM biosynthetic enzyme 5-lipoxygenase (LOX) in vascular cells. Intact human arteries incubated with DHA ex vivo produced 17-hydroxy DHA (17-HDHA) and D-series resolvins, as assessed by liquid chromatography-tandem mass spectrometry. Addition of 17-HDHA to human arteries similarly increased resolvin production. Primary cultures of human saphenous vein endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) converted 17-HDHA to SPMs, including resolvin D1 (RvD1) and other D-series resolvins and protectins. This was accompanied by a rapid translocation of 5-LOX from nucleus to cytoplasm in both ECs and VSMCs, potentially facilitating SPM biosynthesis. Conditioned medium from cells exposed to 17-HDHA inhibited monocyte adhesion to TNF-α–stimulated EC monolayers. These downstream effects were partially reversed by antibodies against the RvD1 receptors ALX/FPR2 and GPR32. These results suggest that autocrine and/or paracrine signaling via locally generated SPMs in the vasculature may represent a novel homeostatic mechanism of relevance to vascular health and disease.—Chatterjee, A., Komshian, S., Sansbury, B. E., Wu, B., Mottola, G., Chen, M., Spite, M., Conte, M. S. Biosynthesis of proresolving lipid mediators by vascular cells and tissues. |
| Databáze: | OpenAIRE |
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