title: The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis.
abstract: 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.
authors.affiliation: Coronary Care Unit, Division of Internal Medicine, Nordland Hospital, 8092 Bodø, Norway; Institute of Clinical Medicine, University of Tromsø, 9019 Tromsø, Norway. Electronic address: anders.w.hovland@gmail.com.
authors.forename: Anders
authors.initials: A
authors.lastname: Hovland
authors.affiliation: Department of Medical and Health Sciences, Linköping University, 581 83 Linköping, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Jonasson
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631 Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.affiliation: Research Institute of Internal Medicine and Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Inflammation Research Centre, University of Oslo, 0318 Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.affiliation: Research Institute of Internal Medicine and Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Inflammation Research Centre, University of Oslo, 0318 Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Coronary Care Unit, Division of Internal Medicine, Nordland Hospital, 8092 Bodø, Norway; Institute of Clinical Medicine, University of Tromsø, 9019 Tromsø, Norway.
authors.forename: Knut T
authors.initials: KT
authors.lastname: Lappegård
authors.affiliation: Norwegian University of Science and Technology, Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, 7491 Trondheim, Norway.
authors.forename: Terje
authors.initials: T
authors.lastname: Espevik
authors.affiliation: Institute of Clinical Medicine, University of Tromsø, 9019 Tromsø, Norway; K.G. Jebsen Inflammation Research Centre, University of Oslo, 0318 Oslo, Norway; Norwegian University of Science and Technology, Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, 7491 Trondheim, Norway; Research Laboratory, Nordland Hospital, 8092 Bodø, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, 0372 Oslo, Norway; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, 9019 Tromsø, Norway.
authors.forename: Tom E
authors.initials: TE
authors.lastname: Mollnes
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D008078:Cholesterol, LDL / Q000378:metabolism; D015926:Complement C3a / Q000378:metabolism; D015936:Complement C5a / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007107:Immune System / Q000276:immunology; D007113:Immunity, Innate; D007249:Inflammation; D018836:Inflammation Mediators / Q000276:immunology; D051379:Mice; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D008078:Cholesterol, LDL; D018836:Inflammation Mediators; D051193:Toll-Like Receptors; D015926:Complement C3a; D015936:Complement C5a; D003165:Complement System Proteins
keywords: Atherosclerosis; Inflammation; The complement system; Toll-like receptors