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The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis
Nordland Hospital, Norway; University of Tromso, Norway.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
Copenhagen University Hospital, Denmark.
National Hospital Norway, Norway; National Hospital Norway, Norway; University of Oslo, Norway.
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2015 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 241, no 2, 480-494 p.Article, review/survey (Refereed) Published
Abstract [en]

Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, may be of particular interest both with respect to pathogenesis and as therapeutic targets in atherosclerosis. Animal studies indicate that inhibition of C3a and C5a reduces atherosclerosis. In humans modified LDL-cholesterol activate complement and TLRs leading to downstream inflammation, and histopathological studies indicate that the innate immune system is present in atherosclerotic lesions. Moreover, clinical studies have demonstrated that both complement and TLRs are upregulated in atherosclerotic diseases, although interventional trials have this far been disappointing. However, based on recent research showing an intimate interplay between complement and TLRs we propose a model in which combined inhibition of both complement and TLRs may represent a potent anti-inflammatory therapeutic approach to reduce atherosclerosis. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD , 2015. Vol. 241, no 2, 480-494 p.
Keyword [en]
The complement system; Toll-like receptors; Atherosclerosis; Inflammation
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-121437DOI: 10.1016/j.atherosclerosis.2015.05.038ISI: 000360100700026PubMedID: 26086357OAI: diva2:855116
Available from: 2015-09-18 Created: 2015-09-18 Last updated: 2015-10-15

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Jonasson, Lena
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Division of Cardiovascular MedicineFaculty of Medicine and Health SciencesDepartment of Cardiology in Linköping
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