PPAR-γ agonist attenuates inflammation in aortic aneurysm patients

Background and objective Peroxisome proliferator-activated receptor (PPAR)-gamma agonist, which is an anti-diabetes drug and reduces expression of tumor necrosis factor (TNF)-alpha, reported to have the effects for anti-inflammation in our body. In cardiovascular fields, this PPAR-c 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-c agonist has anti-inflammatory effects in aorta of patients with aortic aneurysm (AA). Patients and 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-gamma agonist administrating group < n = 6, group Pi, and another is the without group < n = 10, group Ci. PPAR-gamma 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-alpha, 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/beta-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-a, and MMP-9 in both aortic aneurysmal wall and retroperitoneal periaortic fat among group P were significantly decreased. [(Aortic aneurysmal wall; TNF-a; 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-a; 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-c 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.