期刊
ATHEROSCLEROSIS
卷 245, 期 -, 页码 82-87出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2015.12.016
关键词
Inflammation; Extracellular matrix; Immunology; Vascular biology; Atherosclerosis
资金
- Bioiberica
- Fundacio Empreses IQS
- Spanish Ministerium of Economy [SAF2013-43302-R]
- Fundacion Alfonso Martin Escudero
- Beatriu de Pinos Program - AGAUR [2013 BP_A 00051]
- National Institutes of Health [R01 GM49039]
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.
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