title: 15-Deoxy-Δ¹²,¹⁴ prostaglandin J₂ reduces the formation of atherosclerotic lesions in apolipoprotein E knockout mice.
abstract: OBJECTIVE
  15-deoxy-Δ¹²,¹⁴ prostaglandin J₂ (15d-PGJ₂) is a ligand of peroxisome proliferator-activated receptor γ (PPARγ) having diverse effects such as the differentiation of adipocytes and atherosclerotic lesion formation. 15d-PGJ₂ can also regulate the expression of inflammatory mediators on immune cells independent of PPARγ. We investigated the antiatherogenic effect of 15d-PGJ₂.
  
  
  METHODS
  We fed apolipoprotein (apo) E-deficient female mice a Western-type diet from 8 to 16 wk of age and administered 1 mg/kg/day 15d-PGJ₂ intraperitoneally. We measured atherosclerotic lesions at the aortic root, and examined the expression of macrophage and inflammatory atherosclerotic molecules by immunohistochemical and real-time PCR in the lesion.
  
  
  RESULTS
  Atherosclerotic lesion formation was reduced in apo E-null mice treated with 15d-PGJ₂, as compared to in the controls. Immunohistochemical and real-time PCR analyses showed that the expression of MCP-1, TNF-α, and MMP-9 in atherosclerotic lesions was significantly decreased in 15d-PGJ₂ treated mice. The 15d-PGJ₂ also reduced the expression of macrophages and RelA mRNA in atherosclerotic lesions.
  
  
  CONCLUSIONS
  This is the first report 15d-PGJ₂, a natural PPARγ agonist, can improve atherosclerotic lesions in vivo. 15d-PGJ₂ may be a beneficial therapeutic agent for atherosclerosis.
authors: Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Takahiro
authors: T
authors: Seno
authors: Masahide
authors: M
authors: Hamaguchi
authors: Eishi
authors: E
authors: Ashihara
authors: Masataka
authors: M
authors: Kohno
authors: Hidetaka
authors: H
authors: Ishino
authors: Aihiro
authors: A
authors: Yamamoto
authors: Masatoshi
authors: M
authors: Kadoya
authors: Kaoru
authors: K
authors: Nakamura
authors: Ken
authors: K
authors: Murakami
authors: Satoaki
authors: S
authors: Matoba
authors: Taira
authors: T
authors: Maekawa
authors: Yutaka
authors: Y
authors: Kawahito
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012850:Sinus of Valsalva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D001057:Apolipoproteins E; D008055:Lipids; D015230:Prostaglandin D2