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Tytuł:
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Rhamnan sulfate reduces atherosclerotic plaque formation and vascular inflammation.
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Autorzy:
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Patil NP; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Gómez-Hernández A; Department of Biochemistry and Molecular Biology, School of Pharmacy, Complutense University of Madrid, Madrid, Spain.
Zhang F; Departments of Chemistry and Chemical Biology, Chemical and Biological Engineering, Biology, and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Cancel L; Department of Biomedical Engineering, The City College of New York, CUNY, New York, NY, USA.
Feng X; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Yan L; Departments of Chemistry and Chemical Biology, Chemical and Biological Engineering, Biology, and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Xia K; Departments of Chemistry and Chemical Biology, Chemical and Biological Engineering, Biology, and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Takematsu E; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Yang EY; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Le V; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Fisher ME; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Gonzalez-Rodriguez A; Liver Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa, CIBERehd, Madrid, Spain.
Garcia-Monzon C; Liver Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa, CIBERehd, Madrid, Spain.
Tunnell J; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Tarbell J; Department of Biomedical Engineering, The City College of New York, CUNY, New York, NY, USA.
Linhardt RJ; Departments of Chemistry and Chemical Biology, Chemical and Biological Engineering, Biology, and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Baker AB; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA; The Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, TX, USA; Institute for Biomaterials, Drug Delivery and Regenerative Medicine, University of Texas at Austin, Austin, TX, USA. Electronic address: .
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Źródło:
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Biomaterials [Biomaterials] 2022 Dec; Vol. 291, pp. 121865. Date of Electronic Publication: 2022 Oct 28.
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Typ publikacji:
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Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
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Język:
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English
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Imprint Name(s):
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Publication: <1995-> : Amsterdam : Elsevier Science
Original Publication: [Guilford, England] : IPC Science and Technology Press, 1980-
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MeSH Terms:
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Plaque, Atherosclerotic*/drug therapy
Atherosclerosis*/drug therapy
Atherosclerosis*/metabolism
Male ; Female ; Mice ; Animals ; NF-kappa B/metabolism ; Endothelial Cells/metabolism ; Sulfates ; Apolipoproteins E/metabolism ; Inflammation/drug therapy ; Inflammation/metabolism ; Mice, Inbred C57BL
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Grant Information:
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R21 EB023551 United States EB NIBIB NIH HHS; R21 EB024147 United States EB NIBIB NIH HHS; R01 HL141761 United States HL NHLBI NIH HHS
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Contributed Indexing:
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Keywords: Atherosclerosis; Inflammation; Marine polysaccharides; NF-κB pathway; Rhamnan sulfate
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Substance Nomenclature:
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0 (NF-kappa B)
111018-90-7 (rhamnan)
0 (Sulfates)
0 (Apolipoproteins E)
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Entry Date(s):
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Date Created: 20221104 Date Completed: 20221129 Latest Revision: 20221206
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Update Code:
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20240105
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DOI:
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10.1016/j.biomaterials.2022.121865
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PMID:
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36332287
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Objective: While lipid-lowering drugs have become a mainstay of clinical therapy these treatments only slow the progression of the disease and can have side effects. Thus, new treatment options are needed to supplement the effects of lipid lowering therapy for treating atherosclerosis. We examined the use of an inexpensive and widely available marine polysaccharide rhamnan sulfate as an oral therapeutic for limiting vascular inflammation and atherosclerosis.
Methods and Results: We found rhamnan sulfate enhanced the barrier function of endothelial cells, preventing the deposition of LDL and maintaining barrier function even in the presence of glycocalyx-degrading enzymes. Rhamnan sulfate was also found to bind directly to FGF-2, PDGF-BB and NF-κB subunits with high affinity. In addition, rhamnan sulfate was a potent inhibitor of NF-κB pathway activation in endothelial cells by TNF-α. We treated ApoE -/- mice with a high fat diet for 4 weeks and then an addition 9 weeks of high fat diet with or without rhamnan sulfate. Rhamnan sulfate reduced vascular inflammation and atherosclerosis in both sexes of ApoE -/- mice but had a stronger therapeutic effect in female mice. Oral consumption of rhamnan sulfate induced a significant decrease in cholesterol plasma levels in female mice but not in male mice. In addition, there was a marked reduction in inflammation for female mice in the liver and aortic root in comparison to male mice.
Conclusions: Rhamnan sulfate has beneficial effects in reducing inflammation, binding growth factors and NF-κB, enhancing endothelial barrier function and reducing atherosclerotic plaque formation in ApoE -/- mice.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Aaron Baker reports financial support was provided by National Institutes of Health. Aaron Baker reports financial support was provided by US Office of Congressionally Directed Medical Research Programs. Aaron Baker reports financial support was provided by American Heart Association. Robert Linhardt reports financial support was provided by National Institutes of Health.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)