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Atherosclerosis. 2016 Feb;245:82-7. doi: 10.1016/j.atherosclerosis.2015.12.016. Epub 2015 Dec 13.

Treatment with chondroitin sulfate to modulate inflammation and atherogenesis in obesity.

Author information

1
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: pedroml@mit.edu.
2
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Bioengineering Department, Institut Químic de Sarrià, Ramon Llull Univ, Barcelona, Spain.
3
Federal University of São Paulo, Escola Paulista de Medicina, Department of Health Informatics, São Paulo, Brazil.
4
Pre-Clinical R&D Area, Pharmascience Division, Bioibérica SA, Barcelona, Spain.
5
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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.

KEYWORDS:

Atherosclerosis; Extracellular matrix; Immunology; Inflammation; Vascular biology

[Indexed for MEDLINE]
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