title: The Two Faces of Interleukin-17A in Atherosclerosis.
abstract: A complex network of different cytokines and chemokines modulates atherosclerosis, a chronic inflammatory disease. Interleukin-17A (IL-17A) is expressed by different leukocyte subsets such as CD4+IL-17+ T cells (Th17), γδ T cells, natural killer cells, natural killer T cells, and neutrophils. IL-17A plays an important role in host defense and is involved in the pathology of different autoimmune and inflammatory diseases. Recent studies demonstrate an association of IL-17A with atherosclerosis. IL-17A seems to have primarily pro-inflammatory effects in atherogenesis, although there are partially controversial results in the literature. In the murine system, several studies indicate a pro-atherogenic role of IL-17A mediated by increased migration of leukocytes (especially macrophages) into atherosclerotic lesions, increased expression of pro-inflammatory cytokines and chemokines as well as plaque destabilizing matrix-metalloproteinases using Apoe-/- and LDLr-/- mice. In contrast, three studies show atheroprotective effects of IL-17A mediated by downregulation of aortic VCAM-1 expression on endothelial cells and increased collagen production by vascular smooth muscle cells (VSMCs) in LDLr-/- mice. In humans, expression of IL-17A was associated with increased inflammation and plaque vulnerability in human atherosclerotic lesions. Moreover, IL-17A induced a pro-inflammatory, pro-thrombotic, plaque-destabilizing, and cell-attracting response of the inflammatory milieu of human plaque tissue samples. Notably, a recently published study challenged these findings by showing a worse outcome of patients with acute myocardial infarction with low serum levels of IL-17A. In the following review, we will focus on the recent progress of functional studies of IL-17A in atherosclerosis and will try to collect explanations for the controversial data.
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Akhavanpoor
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Akhavanpoor
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Gleissner
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wangler
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Doesch
authors.affiliation: DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Department of Cardiology, Angiology and Pneumology, Medical Clinic III, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Erbel
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D002465:Cell Movement; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D058990:Molecular Targeted Therapy; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; C508717:IL17A protein, human; D020381:Interleukin-17
keywords: Interleukin-17A; anti-atherogenic; atherosclerosis; inflammation; plaque vulnerability; pro-atherogenic