title: The role of complement activation in atherogenesis: the first 40 years.
abstract: The pathogenesis of atherosclerotic inflammation is a multi-step process defined by the interweaving of excess modified lipid particles, monocyte-macrophages populations, and innate immune and adaptive immunity effectors. A part of innate immunity, the complement system, is an important player in the induction and progression of atherosclerosis. The accumulation of either oxidized or enzymatically modified LDL-bound to C-reactive protein or not-prompts complement activation leading to the assembly of the terminal complement C5b-9 complex in the atherosclerotic lesion. The sublytic C5b-9 assembly leads to the activation and proliferation of smooth muscle and endothelial cells, accompanied by the release of various chemotactic, pro-adhesion, and procoagulant cytokines from these cells. Response gene to complement (RGC)-32, an essential effector of the terminal complement complex C5b-9, also affects atherogenesis, propelling vascular smooth muscle cell proliferation and migration, stimulating endothelial proliferation, and promoting vascular lesion formation. A substantial amount of experimental work has suggested a role for the complement system activation during atherosclerotic plaque formation, with the proximal classical complement pathway seemingly having a protective effect and terminal complement contributing to accelerated atherogenesis. All these data suggest that complement plays an important role in atherogenesis.
authors.affiliation: Department of Neurology, School of Medicine Baltimore, University of Maryland, 655 W. Baltimore Street, Baltimore, MD, 21201, USA.|Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Vlaicu
authors.affiliation: Department of Neurology, School of Medicine Baltimore, University of Maryland, 655 W. Baltimore Street, Baltimore, MD, 21201, USA.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Tatomir
authors.affiliation: Division of Rheumatology and Immunology, Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Violeta
authors.initials: V
authors.lastname: Rus
authors.affiliation: Department of Neurology, School of Medicine Baltimore, University of Maryland, 655 W. Baltimore Street, Baltimore, MD, 21201, USA.|Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA.
authors.forename: Armugam P
authors.initials: AP
authors.lastname: Mekala
authors.affiliation: Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Petru A
authors.initials: PA
authors.lastname: Mircea
authors.affiliation: Division of Rheumatology and Immunology, Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Florin
authors.initials: F
authors.lastname: Niculescu
authors.affiliation: Department of Neurology, School of Medicine Baltimore, University of Maryland, 655 W. Baltimore Street, Baltimore, MD, 21201, USA. hrus@umaryland.edu.|Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA. hrus@umaryland.edu.|Veterans Administrdtion Multiple Sclerosis Center of Excellence, Baltimore, MD, USA. hrus@umaryland.edu.
authors.forename: Horea
authors.initials: H
authors.lastname: Rus
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics; D008078:Cholesterol, LDL / Q000378:metabolism; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D008078:Cholesterol, LDL; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C115049:RGCC protein, human; D003165:Complement System Proteins
keywords: Atherosclerosis; C5b-9 complement complex; Complement activation; Endothelial cells; RGC-32; Smooth muscle cells