title: Role of interleukin 17 in inflammation, atherosclerosis, and vascular function in apolipoprotein e-deficient mice.
abstract: OBJECTIVE
  Interleukin 17A (IL17A) is involved in many inflammatory processes, but its role in atherosclerosis remains controversial. We examined the role of IL17A in mouse and human atherosclerosis.
  
  
  RESULTS
  Atherosclerosis was induced in apolipoprotein E (ApoE)(-/-) and IL17A/ApoE(-/-) mice using high-fat feeding, angiotensin II infusion, or partial carotid ligation. In ApoE(-/-) mice, 3 months of high-fat diet induced interferon-γ production by splenic lymphocytes, and this was abrogated in IL17A/ApoE(-/-) mice. IL17A/ApoE(-/-) mice had reduced aortic superoxide production, increased aortic nitric oxide levels, decreased aortic leukocyte and dendritic cell infiltration, and reduced weight gain after a high-fat diet compared with ApoE(-/-) mice. Despite these favorable effects, IL17A deficiency did not affect aortic plaque burden after a high-fat diet or angiotensin II infusion. In a partial carotid ligation model, IL17A deficiency did not affect percentage of stenosis but reduced outward remodeling. In this model, neutralization of the related isoform, IL17F, in IL17A/ApoE(-/-) mice did not alter atherosclerosis. Finally, there was no correlation between IL17A levels and carotid intima-media thickness in humans.
  
  
  CONCLUSIONS
  IL17 contributes to vascular and systemic inflammation in experimental atherosclerosis but does not alter plaque burden. The changes in plaque composition caused by IL17 might modulate plaque stability.
authors.affiliation: Division of Cardiology, Emory University, Atlanta, GA, USA.
authors.forename: Meena S
authors.initials: MS
authors.lastname: Madhur
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Funt
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Antony
authors.initials: A
authors.lastname: Vinh
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Heinrich E
authors.initials: HE
authors.lastname: Lob
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Yelena
authors.initials: Y
authors.lastname: Blinder
authors.forename: Ayaz
authors.initials: A
authors.lastname: Rahman
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
mesh_terms: D000368:Aged; D000804:Angiotensin II; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D001011:Aorta / Q000276:immunology / Q000378:metabolism; D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000601:surgery; D002340:Carotid Artery Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004041:Dietary Fats; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood* / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008026:Ligation; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
chemical_list: D057134:Antibodies, Neutralizing; D001057:Apolipoproteins E; D004041:Dietary Fats; C508717:IL17A protein, human; C098680:Il17a protein, mouse; C515932:Il17f protein, mouse; D020381:Interleukin-17; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D007371:Interferon-gamma