Treatment with chondroitin sulfate to modulate inflammation and atherogenesis in obesity

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism
  • Cell Line
  • Chondroitin Sulfates / therapeutic use*
  • Disease Models, Animal
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Male
  • Mice
  • Mice, Obese
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / pathology


  • Chondroitin Sulfates