The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis. / Hovland, Anders; Jonasson, Lena; Garred, Peter; Yndestad, Arne; Aukrust, Pål; Lappegård, Knut T; Espevik, Terje; Mollnes, Tom E.
I: Atherosclerosis, Bind 241, Nr. 2, 08.2015, s. 480-94.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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T1 - The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis
AU - Hovland, Anders
AU - Jonasson, Lena
AU - Garred, Peter
AU - Yndestad, Arne
AU - Aukrust, Pål
AU - Lappegård, Knut T
AU - Espevik, Terje
AU - Mollnes, Tom E
N1 - Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
PY - 2015/8
Y1 - 2015/8
N2 - 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.
AB - 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.
KW - Animals
KW - Atherosclerosis
KW - Cholesterol, LDL
KW - Complement C3a
KW - Complement C5a
KW - Complement System Proteins
KW - Disease Models, Animal
KW - Humans
KW - Immune System
KW - Immunity, Innate
KW - Inflammation
KW - Inflammation Mediators
KW - Mice
KW - Signal Transduction
KW - Toll-Like Receptors
U2 - 10.1016/j.atherosclerosis.2015.05.038
DO - 10.1016/j.atherosclerosis.2015.05.038
M3 - Review
C2 - 26086357
VL - 241
SP - 480
EP - 494
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 2
ER -
ID: 162840044