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

Pedro Melgar-Lesmes; Alvaro Sánchez-Herrero; Ferran Lozano-Juan; Jose María de la Torre Hernández; Eulàlia Montell; Wladimiro Jiménez; Elazer R. Edelman; Mercedes Balcells

doi:10.1055/s-0038-1657753

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

¹Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States

²Department of Biomedicine, Fundació Clínic per a la Recerca Biomèdica, University of Barcelona, Barcelona, Spain

,

Alvaro Sánchez-Herrero

¹Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States

,

Ferran Lozano-Juan

¹Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States

,

Jose María de la Torre Hernández

³Hospital Marqués de Valdecilla University Hospital, Universidad de Cantabria, Santander, Spain

,

Eulàlia Montell

⁴Pre-Clinical R&D Area, Bioibérica S.A.U., Barcelona, Spain

,

Wladimiro Jiménez

⁵Biochemistry and Molecular Genetics Service, Department of Biomedicine, Hospital Clínic Universitari, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain

,

Elazer R. Edelman

¹Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States

⁶Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

,

Mercedes Balcells

¹Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States

⁷Department of Biological Engineering, IQS School of Engineering, Universitat Ramon Llull, Barcelona, Spain

› Institutsangaben

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

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