title: Chronic administration of methamphetamine promotes atherosclerosis formation in ApoE-/- knockout mice fed normal diet.
abstract: OBJECTIVE
  Chronic methamphetamine (METH) abuse could induce neurotoxicity due to reactive oxygen species generation and sympathetic activation. Both factors are associated with atherosclerosis, so we tested the hypothesis that chronic METH administration might also promote atherosclerosis formation in Apo E-/- knockout mice fed normal diet.
  
  
  RESULTS
  Male ApoE-/- mice (6 weeks-old) were treated with saline (NS) or METH [4 mg/kg/day (M4) or 8 mg/kg/day (M8) through intraperitoneal injection] for 24 weeks. Atherosclerotic lesion area on oil red O stained en face aorta was dose-dependently increased in M4 and M8 groups compared to NS group. Percentage of atherosclerotic lesion area was significantly higher in M8 group compared to NS and M4 groups. Plasma CRP was increased and inflammatory cytokine (ICAM-1, VCAM-1, TNF-α, and INF-γ) expression on aortic root was upregulated in METH groups compared to NS group. Neuropeptide Y (NPY) protein and mRNA expressions in aortic root and myocardial tissue were determined by Western blot and real time PCR, which were significantly upregulated in M4 and M8 groups. Moreover, mRNA expressions of NPY1R, NPY2R and NPY5R in aortic and myocardial tissue were also significantly upregulated in M4 and M8 groups. Raw264.7 cells were treated with NPY, NPY receptor antagonists, METH (10 μM or 100 μM) with or without lipopolysaccharide (LPS), and the expressions of TNF-α, CRP, MCP-1 and reactive oxygen species (ROS) production were significantly increased in METH and LPS + METH groups compared to control and LPS groups. Co-treatment with NPY1R antagonist decreased the expressions of TNF-α, CRP and MCP-1 in NPY and METH treated cells.
  
  
  CONCLUSIONS
  Chronic METH administration can promote inflammation and atherosclerotic plague formation in ApoE-/- mice fed normal chow. NPY might be involved in the pathogenesis of METH-induced atherogenic effects through NPY Y1 receptor pathway.
authors.affiliation: Department of Cardiology, Heart Center at Puai Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Heart Center at Puai Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Lun
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cardiology, Heart Center at Puai Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Heart Center at Puai Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Heart Center at Puai Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Lingbo
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Cardiology, Heart Center at Puai Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Heart Center at Puai Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Heart Center at Puai Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: Pxhong01@hotmail.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Cardiology, Heart Center at Puai Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yegu2003cn@163.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000821:Animal Feed; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics*; D001835:Body Weight; D002097:C-Reactive Protein / Q000378:metabolism; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000502:physiology; D007150:Immunohistochemistry; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D009478:Neuropeptide Y / Q000097:blood* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013566:Sympathomimetics / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D009478:Neuropeptide Y; D017382:Reactive Oxygen Species; D013566:Sympathomimetics; D014409:Tumor Necrosis Factor-alpha; D008694:Methamphetamine; D002097:C-Reactive Protein
keywords: Atherosclerosis; Methamphetamine; NPY; NPYR