title: Regulation of atherosclerotic plaque inflammation.
abstract: The immune reactions that regulate atherosclerotic plaque inflammation involve chemokines, lipid mediators and costimulatory molecules. Chemokines are a family of chemotactic cytokines that mediate immune cell recruitment and control cell homeostasis and activation of different immune cell types and subsets. Chemokine production and activation of chemokine receptors form a positive feedback mechanism to recruit monocytes, neutrophils and lymphocytes into the atherosclerotic plaque. In addition, chemokine signalling affects immune cell mobilization from the bone marrow. Targeting several of the chemokines and/or chemokine receptors reduces experimental atherosclerosis, whereas specific chemokine pathways appear to be involved in plaque regression. Leukotrienes are lipid mediators that are formed locally in atherosclerotic lesions from arachidonic acid. Leukotrienes mediate immune cell recruitment and activation within the plaque as well as smooth muscle cell proliferation and endothelial dysfunction. Antileukotrienes decrease experimental atherosclerosis, and recent observational data suggest beneficial clinical effects of leukotriene receptor antagonism in cardiovascular disease prevention. By contrast, other lipid mediators, such as lipoxins and metabolites of omega-3 fatty acids, have been associated with the resolution of inflammation. Costimulatory molecules play a central role in fine-tuning immunological reactions and mediate crosstalk between innate and adaptive immunity in atherosclerosis. Targeting these interactions is a promising approach for the treatment of atherosclerosis, but immunological side effects are still a concern. In summary, targeting chemokines, leukotriene receptors and costimulatory molecules could represent potential therapeutic strategies to control atherosclerotic plaque inflammation.
authors.affiliation: Translational Cardiology, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bäck
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilians University, Munich, Germany.|German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.|Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Weber
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilians University, Munich, Germany.|German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.|Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Lutgens
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D018925:Chemokines / Q000145:classification / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D015289:Leukotrienes / Q000378:metabolism; D044045:Lipoxins / Q000378:metabolism; D019899:Paracrine Communication; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000503:physiopathology; D019707:Receptors, Chemokine / Q000145:classification / Q000378:metabolism
chemical_list: D018925:Chemokines; D015289:Leukotrienes; D044045:Lipoxins; D019707:Receptors, Chemokine
keywords: chemokines; costimulatory molecules; leukotrienes; lipoxins; lipoxygenase