Chondroitin Sulphate Attenuates Atherosclerosis in ApoE Knockout Mice Involving Cellular Regulation of the Inflammatory Response
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nihms-984113.pdf
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Accepted version
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1.46 MB
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Author(s)
Melgar Lesmes, Pedro
Sanchez Herrero, Alvaro
Lozano Juan, Ferran
de la Torre Hernández, Jose
Montell, Eulàlia
Jiménez, Wladimiro
Edelman, Elazer R
Balcells-Camps, Mercedes
Date Issued
June 2018
Journal
Thrombosis and Haemostatis
Publisher
Georg Thieme Verlag KG
Citation
Melgar-Lesmes, Pedro et al. "Chondroitin Sulphate Attenuates Atherosclerosis in ApoE Knockout Mice Involving Cellular Regulation of the Inflammatory Response." Thrombosis and Haemostatis 118, 7 (June 2018): 1329-1339 © 2018 Georg Thieme Verlag KG
Version
Author's final manuscript
Abstract
Chondroitin sulphate (CS) has long been used to treat osteoarthritis. Some investigations have also shown that the treatment with CS could reduce coronary events in patients with heart disease but no studies have identified the mechanistic role of these therapeutic effects. We aimed to investigate how the treatment with CS can interfere with the progress of atherosclerosis. The aortic arch, thoracic aorta and serum were obtained from apolipoprotein E (ApoE) knockout mice fed for 10 weeks with high-fat diet and then treated with CS (300 mg/kg, n = 15) or vehicle (n = 15) for 4 weeks. Atheromatous plaques were highlighted in aortas with Oil Red staining and analysed by microscopy. ApoE knockout mice treated with CS exhibited attenuated atheroma lesion size by 68% as compared with animals receiving vehicle. Serum lipids, glucose and C-reactive protein were not affected by treatment with CS. To investigate whether CS locally affects the inflamed endothelium or the formation of foam cells in plaques, human endothelial cells and monocytes were stimulated with tumour necrosis factor α or phorbol myristate acetate in the presence or absence of CS. CS reduced the expression of vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and ephrin-B2 and improved the migration of inflamed endothelial cells. CS inhibited foam cell formation in vivo and concomitantly CD36 and CD146 expression and oxidized low-density lipoprotein uptake and accumulation in cultured activated human monocytes and macrophages. Reported cardioprotective effects of CS may arise from modulation of pro-inflammatory activation of endothelium and monocytes and foam cell formation.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
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DOI of Published Version
https://doi.org/10.1055/s-0038-1657753
