Pioglitazone preserves vein graft integrity in a rat aortic interposition model

Objective

Improvement of vein graft patency may be highly beneficial in coronary artery bypass grafting, but graft degeneration is considered to be one of the main pathophysiologic causes for vein graft failure. Because peroxisome proliferator-activated receptor-γ activator pioglitazone was recently reported to possess pleiotropic protective effects on various organs and tissues, we conducted experiments to test the hypothesis that pioglitazone could prevent graft degeneration, leading to the preservation of vein graft integrity.

Methods

In a rat aortic interposition model with autologous femoral vein, pioglitazone (3 mg/kg/d) or vehicle (normal saline) was given to rats by gastric gavage once per day beginning 3 days before surgery and ending 8 weeks after surgery. Vein graft degeneration and remodeling were assessed at 24 hours, 7 days, 8 weeks, and 6 months after surgery.

Results

At 24 hours, pioglitazone significantly reduced endothelial desquamation, reactive oxygen species generation, myeloperoxidase activity, and lipid peroxidation in vein grafts. At 7 days, mRNA expression and gelatinolytic activity of matrix metalloproteinase-2 and 9 in vein grafts were significantly suppressed by pioglitazone treatment. Immunofluorescent staining showed that pioglitazone enhanced peroxisome proliferator-activated receptor-γ expression in vein grafts at 8 weeks, especially in their intimal side. At 6 months, pioglitazone treatment prevented graft dilation (52.3% ± 3.1% vs 90.7% ± 9.9%, P = .0041) and neointimal hyperplasia (14.6% ± 1.3% vs 29.9% ± 2.9%, P = .0008), and increased graft flow velocity ratio (0.86 ± 0.03 vs 0.59 ± 0.04, P < .0001), compared with vehicle treatment.

Conclusion

Pioglitazone prevents graft degeneration under arterial pressure stress and preserves the vein graft integrity in a rat aortic interposition model.

Abbreviations and Acronyms: CABG, coronary artery bypass grafting, MMP, matrix metalloproteinase, PPAR, peroxisome proliferator-activated receptor, SMA, smooth muscle actin, SMC, smooth muscle cell, TIMP, tissue inhibitor of matrix metalloproteinase