title: Heat shock protein 65 promotes atherosclerosis through impairing the properties of high density lipoprotein.
abstract: OBJECTIVE
  To explicit whether the functions of high density lipoprotein (HDL) are impaired in murine atherosclerosis by subcutaneous immunization with recombinant mycobacterial heat shock protein 65 (HSP65).
  
  
  METHODS
  C57BL/6 mice were fed a normal chow-diet with non immunization as normal group. ApoE knockout (ApoE(-/-)) mice on high-fat diet were randomly divided into three groups (n = 8) and immunized subcutaneously with different concentrations of HSP65 or phosphate-buffered saline (PBS). All animals were treated for 16 weeks. Reverse cholesterol efflux, the anti-oxidant and anti-inflammatory functions of HDL were assayed. Hepatocytes and peritoneal macrophages were isolated to examine the expression of cholesterol transport regulating proteins, including SR-B1, ABCA1, ABCG1, PPAR-γ and LXR-α.
  
  
  RESULTS
  In HSP65-immunized mice, paraoxonase1 (PON1) activity and the expression of IL-10 were reduced, while High-density lipoprotein inflammatory index (HII), myeloperoxidase (MPO) activity, and the expression of IFN-γ were elevated gradually. The MPO/PON1 ratio amount was significantly higher in HSP65-immunized group than in normal or PBS-immunized group. In addition, compared with normal or PBS-immunized group, cholesterol efflux rate and the expression of regulating proteins were markedly decreased in HSP65-immunized group. The mice immunized with HSP65 developed significantly larger aorta atherosclerotic plaques when compared with PBS-treated littermates. The high MPO/PON1 ratio was correlated with HII, cholesterol efflux rate and atherosclerotic plaques.
  
  
  CONCLUSIONS
  This study demonstrates that subcutaneous immunization with HSP65 impairs the properties of HDL, which may contribute to its important pathogenic role of HSP65 in atherogenesis. Also, MPO/PON1 ratio may be a predictor of AS.
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
authors.forename: Haige
authors.initials: H
authors.lastname: Sun
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Hong Kong.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
authors.forename: Tingrong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Tian
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Luo
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Lai
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Dai
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China. Electronic address: guozhigang126@126.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001057:Apolipoproteins E / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000378:metabolism; D050197:Atherosclerosis; D001426:Bacterial Proteins / Q000378:metabolism*; D018834:Chaperonin 60 / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D011994:Recombinant Proteins; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C074119:heat-shock protein 65, Mycobacterium; D007371:Interferon-gamma; D002784:Cholesterol; D009195:Peroxidase; D043303:Aryldialkylphosphatase; C560867:PON1 protein, mouse
keywords: Atherosclerosis; Cholesterol efflux; Heat shock protein 65; High density lipoprotein