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Thromb Haemost 2018; 118(07): 1329-1339
DOI: 10.1055/s-0038-1657753
Atherosclerosis and Ischaemic Disease
Georg Thieme Verlag KG Stuttgart · New York

Chondroitin Sulphate Attenuates Atherosclerosis in ApoE Knockout Mice Involving Cellular Regulation of the Inflammatory Response

Pedro Melgar-Lesmes
1   Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
2   Department of Biomedicine, Fundació Clínic per a la Recerca Biomèdica, University of Barcelona, Barcelona, Spain
,
Alvaro Sánchez-Herrero
1   Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
,
Ferran Lozano-Juan
1   Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
,
Jose María de la Torre Hernández
3   Hospital Marqués de Valdecilla University Hospital, Universidad de Cantabria, Santander, Spain
,
Eulàlia Montell
4   Pre-Clinical R&D Area, Bioibérica S.A.U., Barcelona, Spain
,
Wladimiro Jiménez
5   Biochemistry and Molecular Genetics Service, Department of Biomedicine, Hospital Clínic Universitari, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
,
Elazer R. Edelman
1   Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
6   Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Mercedes Balcells
1   Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
7   Department of Biological Engineering, IQS School of Engineering, Universitat Ramon Llull, Barcelona, Spain
› Author Affiliations Funding This work was supported by a grant from Spanish Ministerium of Economy (SAF2013–43302-R) and by Bioibérica and Fundacio Empreses IQS to M.B.; National Institutes of Health (R01 GM 49039) to E.R.E.; Ministerio de Economia y Competitividad (SAF2015–64126-R) to W.J.; European Association for the Study of Liver (EASL), Generalitat de Catalunya (PERIS SLT002/16/00341) and Beatriu de Pinos Program 2016 (BP-00236) to P.M.-L.
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Publication History

26 February 2018

23 April 2018

Publication Date:
06 June 2018 (online)

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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.

Keywords

atherosclerosis - inflammation - chondroitin sulphate - immunology - vascular biology

Supplementary Material

 

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