Abstract 1681: PPAR-γ Agonist, Pioglitazone, Attenuates Neointimal Area by Suppression of the Early Inflammatory Response in a Porcine Coronary Stent Model
Background: Enhanced inflammatory reactions accelerated the neointimal hyperplasia after vascular injury. Peroxisome proliferators activator receptor (PPAR)-γ agonists, pioglitazone, have antiatherogenic effects through the inhibition of the production of inflammatory cytokines. We hypothesized that pioglitazone might inhibit the early inflammatory response, resulting in prevention of neointimal hyperplasia after stenting in porcine coronary stent model.
Methods&Results: Pioglitazone (150 mg/day) or placebo was administered orally to 10 pigs (30 coronaries) in each, from 7 days before stenting until the time of euthanasia at 3 or 28 days after stenting. The coronary artery of the pigs was injured with an oversized bare metal stent. Insulin sensitivity was greater in pioglitazone -treated pigs than in untreated pigs (Kitt 5.87±0.68 versus 4.14±1.66, P=0.003), whereas fasting blood glucose did not differ between groups. These findings suggest that pioglitazone enhanced systemic insulin sensitivity. Acute inflammatory cell adhesion on the surface of the stent site was evaluated by scanning electron microscopy and was significantly suppressed in pioglitazone- treated group comparing with the control (% of site occurring greater infiltration: 40.8 versus 60.9%, P=0.002). In addition, immunohistochemistry revealed that MCP-1 expression in the media was of significantly less in the treatment group than in the control group. On Day 28, intravascular ultrasound analysis showed pioglitazone significantly reduced neointimal area at the stent site than in the control (2.96±1.07 versus 4.03±1.15mm2, P=0.006). Morphometric assessment of stent-section also showed significantly decreased in neointimal area and %stenosis in the pioglitazone group compared to the control (neointimal area: 1.85±0.58 versus 3.10±1.21mm2, P=0.0018, %stenosis: 31.8 versus 44.4%, P=0.025), whereas there were no difference in the mean injury score between two groups.
Conclusion: Pioglitazone inhibited neointimal hyperplasia after stenting through a reduction of early inflammatory reactions.