Treatment with chondroitin sulfate to modulate inflammation and atherogenesis in obesity

Treatment with chondroitin sulfate to modulate inflammation and atherogenesis in obesity

Author Melgar-Lesmes, Pedro Google Scholar
Garcia-Polite, Fernando Google Scholar
Del-Rey-Puech, Paula Google Scholar
Rosas, Elisabet Google Scholar
Dreyfuss, Juliana L. Autor UNIFESP Google Scholar
Montell, Eulalia Google Scholar
Verges, Josep Google Scholar
Edelman, Elazer R. Google Scholar
Balcells, Mercedes Google Scholar
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-alpha 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 IL1 beta by 70%, TNF-alpha by 82% and selected chemokines by 25-35%. Cultures of coronary endothelial cells and monocytes stimulated with TNF-alpha secreted less pro-inflammatory cytokines in the presence of CS (P < 0.01). CS reduced the activation of the TNF-alpha signaling pathway in endothelial cells (pErk 36% of reduction, and NF kappa B 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-alpha thus reducing the propagation of inflammation and preventing the formation of atherosclerotic plaques. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords Inflammation
Extracellular matrix
Vascular biology
xmlui.dri2xhtml.METS-1.0.item-coverage Clare
Language English
Sponsor Bioiberica
Fundacio Empreses IQS
Spanish Ministerium of Economy
Fundacion Alfonso Martin Escudero
Beatriu de Pinos Program - AGAUR
National Institutes of Health
Grant number Spanish Ministerium of Economy: SAF2013-43302
Beatriu de Pinos Program - AGAUR: 2013 BP_A 00051
National Institutes of Health: R01 GM49039
Date 2016
Published in Atherosclerosis. Clare, v. 245, p. 82-87, 2016.
ISSN 0021-9150 (Sherpa/Romeo, impact factor)
Publisher Elsevier Ireland Ltd
Extent 82-87
Access rights Closed access
Type Article
Web of Science ID WOS:000368982400034

Show full item record


File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)




My Account