dc.contributor.author | Rosas, Elisabet | |
dc.contributor.author | Dreyfuss, Juliana L. | |
dc.contributor.author | Montell, Eulàlia | |
dc.contributor.author | Vergés, Josep | |
dc.contributor.author | Balcells, Mercedes | |
dc.contributor.author | Melgar Lesmes, Pedro | |
dc.contributor.author | Garcia Polite, Fernando | |
dc.contributor.author | Del Rey Puech, Paula | |
dc.contributor.author | Rosas, Elisabet Canyelles | |
dc.contributor.author | Edelman, Elazer R | |
dc.date.accessioned | 2017-12-14T20:07:33Z | |
dc.date.available | 2017-12-14T20:07:33Z | |
dc.date.issued | 2015-12 | |
dc.date.submitted | 2015-12 | |
dc.identifier.issn | 0021-9150 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/112764 | |
dc.description.abstract | Background and aims: Osteoarthritic patients treated with high doses of chondroitin sulfate (CS) have a lower incidence of coronary heart disease - but the mechanistic aspects of these beneficial effects of CS remain undefined. We examined how CS treatment affects the formation of atheroma via interaction with endothelial cells and monocytes. Methods: We characterized arterial atheromatous plaques by multiphoton microscopy and serum pro-inflammatory cytokines by immunoenzymatic techniques in obese mice receiving CS (1 g/kg/day, i.p.) or vehicle for 6 days. Effects of CS on signaling pathways, cytokine secretion and macrophage migration were evaluated in cultures of human coronary endothelial cells and in a monocyte cell line stimulated with TNF-α by Western blot, immunoenzymatic techniques and transwell migration assays. Results: Treatment of obese mice with CS reduced the extension of foam cell coverage in atheromatous plaques of arterial bifurcations by 62.5%, the serum concentration of IL1β by 70%, TNF-α by 82% and selected chemokines by 25-35%. Cultures of coronary endothelial cells and monocytes stimulated with TNF-α secreted less pro-inflammatory cytokines in the presence of CS (P < 0.01). CS reduced the activation of the TNF-α signaling pathway in endothelial cells (pErk 36% of reduction, and NFκB 33% of reduction), and the migration of activated monocytes to inflamed endothelial cells in transwells (81 ± 6 vs. 13 ± 2, P < 0.001). Conclusions: CS interferes with the pro-inflammatory activation of monocytes and endothelial cells driven by TNF-α thus reducing the propagation of inflammation and preventing the formation of atherosclerotic plaques. | en_US |
dc.publisher | Elsevier BV | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/J.ATHEROSCLEROSIS.2015.12.016 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | Treatment with chondroitin sulfate to modulate inflammation and atherogenesis in obesity | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Melgar-Lesmes, Pedro, et al. “Treatment with Chondroitin Sulfate to Modulate Inflammation and Atherogenesis in Obesity.” Atherosclerosis, vol. 245, Feb. 2016, pp. 82–87. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Institute for Medical Engineering & Science | en_US |
dc.contributor.department | Harvard University--MIT Division of Health Sciences and Technology | en_US |
dc.contributor.mitauthor | Melgar Lesmes, Pedro | |
dc.contributor.mitauthor | Garcia Polite, Fernando | |
dc.contributor.mitauthor | Del Rey Puech, Paula | |
dc.contributor.mitauthor | Rosas, Elisabet Canyelles | |
dc.contributor.mitauthor | Edelman, Elazer R | |
dc.relation.journal | Atherosclerosis | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2017-12-14T17:21:33Z | |
dspace.orderedauthors | Melgar-Lesmes, Pedro; Garcia-Polite, Fernando; Del-Rey-Puech, Paula; Rosas, Elisabet; Dreyfuss, Juliana L.; Montell, Eulàlia; Vergés, Josep; Edelman, Elazer R.; Balcells, Mercedes | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-2009-5911 | |
dc.identifier.orcid | https://orcid.org/0000-0002-7832-7156 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |