PPAR-γ agonist attenuates inflammation in aortic aneurysm patients.
Gen Thorac Cardiovasc Surg
; 63(10): 565-71, 2015 Oct.
Article
de En
| MEDLINE
| ID: mdl-26213347
ABSTRACT
BACKGROUND AND 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). PATIENTS ANDMETHODS:
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/ß-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)].CONCLUSION:
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.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Anévrysme de l'aorte
/
Aortite
/
Thiazolidinediones
/
Récepteur PPAR gamma
Type d'étude:
Diagnostic_studies
Aspects:
Ethics
Limites:
Aged
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Gen Thorac Cardiovasc Surg
Sujet du journal:
ANGIOLOGIA
/
CARDIOLOGIA
Année:
2015
Type de document:
Article
Pays d'affiliation:
Japon