title: Human apolipoprotein A-II protects against diet-induced atherosclerosis in transgenic rabbits.
abstract: OBJECTIVE
  Apolipoprotein (apo) A-II is the second major apo of high-density lipoproteins, yet its pathophysiological roles in the development of atherosclerosis remain unknown. We aimed to examine whether apo A-II plays any role in atherogenesis and, if so, to elucidate the mechanism involved.
  
  
  RESULTS
  We compared the susceptibility of human apo A-II transgenic (Tg) rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermate rabbits. Tg rabbits developed significantly less aortic and coronary atherosclerosis than their non-Tg littermates, while total plasma cholesterol levels were similar. Atherosclerotic lesions of Tg rabbits were characterized by reduced macrophages and smooth muscle cells, and apo A-II immunoreactive proteins were frequently detected in the lesions. Tg rabbits exhibited low levels of plasma C-reactive protein and blood leukocytes compared with non-Tg rabbits, and high-density lipoproteins of Tg rabbit plasma exerted stronger cholesterol efflux activity and inhibitory effects on the inflammatory cytokine expression by macrophages in vitro than high-density lipoproteins isolated from non-Tg rabbits. In addition, β-very-low-density lipoproteins of Tg rabbits were less sensitive to copper-induced oxidation than β-very-low-density lipoproteins of non-Tg rabbits.
  
  
  CONCLUSIONS
  These results suggest that enrichment of apo A-II in high-density lipoprotein particles has atheroprotective effects and apo A-II may become a target for the treatment of atherosclerosis.
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato, Chuo-City, Yamanashi, Japan.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Manabu
authors.initials: M
authors.lastname: Niimi
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Nishijima
authors.forename: Ahmed Bilal
authors.initials: AB
authors.lastname: Waqar
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.forename: Tomonari
authors.initials: T
authors.lastname: Koike
authors.forename: Shuji
authors.initials: S
authors.lastname: Kitajima
authors.forename: Enqi
authors.initials: E
authors.lastname: Liu
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Inoue
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kohashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Keyamura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Loretta
authors.initials: L
authors.lastname: Ma
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zha
authors.forename: Teruo
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Asada
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001011:Aorta / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D002791:Cholesterol, Dietary / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D010084:Oxidation-Reduction; D058226:Plaque, Atherosclerotic; D011817:Rabbits; D013997:Time Factors
chemical_list: C115794:APOA2 protein, human; D016633:Apolipoprotein A-II; D002791:Cholesterol, Dietary; D016207:Cytokines; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C099252:oxidized low density lipoprotein