title: PPAR-γ agonist attenuates inflammation in aortic aneurysm patients.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor (PPAR) -γ agonist, which is an anti-diabetes drug and reduces expression of tumor necrosis factor (TNF)-α, reported to have the effects for anti-inflammation in our body. In cardiovascular fields, this PPAR-γ agonist already reported to suppress progression of coronary atherosclerosis. Various cytokines, which is secreted from fat tissues around artery, promote atherosclerosis and/or aneurysmal changes in aorta/artery. Objective of our study is to clarify whether PPAR-γ agonist has anti-inflammatory effects in aorta of patients with aortic aneurysm (AA).
  
  
  METHODS
  The medical ethics committee in Tokushima University Hospital approved protocol for this study. Sixteen patients with AA (more than 5 cm in diameter, scheduled open surgery) were divided into two groups; one is PPAR-γ agonist administrating group [Formula: see text] n = 6, group P[Formula: see text], and another is the without group [Formula: see text] n = 10, group C[Formula: see text]. PPAR-γ agonist, whose dose was 15 mg/day, was administrated in the group P for more than 2 months before aneurysectomy and grafting (mean; 4.2 ± 3.4 months) (Supplemental Table 1). Biopsy specimens were obtained from abdominal subcutaneous fat, greater omentum, retroperitoneal periaortic fat and aneurysmal wall in surgical procedure. Blood examination also achieved before/after procedure. Harvested specimens were analyzed with histology (HE and EVG), immunohistochemistry (macrophage) and RT-PCR (adiponectin, MCP-1, TNF-α, CD68, matrix metalloprotease (MMP)-2, MMP-9).
  
  
  RESULTS
  Macrophage infiltration in aortic wall and retroperitoneal periaortic fat among group P was significantly decreased compared to that among group C. Adiponectin expressions in both subcutaneous fat and retroperitoneal periaortic fat among the group P (adiponectin/β-actin) were significantly increased compared to those among the group C [subcutaneous fat; 16.8 ± 13.9 vs. 5.82 ± 2.94 (P = 0.04), retroperitoneal periaortic fat; 21.3 ± 24.1 vs. 2.12 ± 1.69 (P = 0.04)]. On the other hand, expressions of TNF-α, and MMP-9 in both aortic aneurysmal wall and retroperitoneal periaortic fat among group P were significantly decreased. [(Aortic aneurysmal wall; TNF-α; 0.45 ± 0.15 vs. 5.18 ± 3.49 (P = 0.02), MMP-9; 39.6 ± 69.0 vs. 721 ± 741 (P = 0.04)], [retroperitoneal periaortic fat; TNF-α; 1.14 ± 0.36 vs. 26.4 ± 25.0 (P = 0.048), MMP-9; 0.18 ± 0.21 vs. 50.0 ± 41.8 (P = 0.047)].
  
  
  CONCLUSIONS
  These data may indicate that PPAR-γ agonist become the way for preventing or delaying aortic aneurysm progression in patients. More studies will be needed to clarify this drug effects in detail.
authors.affiliation: Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Motoki
authors.affiliation: Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan. hirotsugu.kurobe@tokushima-u.ac.jp.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kurobe
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Kinoshita
authors.affiliation: Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Rocco
authors.affiliation: Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sogabe
authors.affiliation: Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Hori
authors.affiliation: Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.affiliation: Department of Cardiovascular Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kitagawa
mesh_terms: D000368:Aged; D001014:Aortic Aneurysm / Q000175:diagnosis / Q000188:drug therapy*; D001025:Aortitis / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: Aortic aneurysm; Inflammation; Macrophage; PPAR-gamma agonist