Abstract 17580: Pioglitazone Prevents Intimal Hyperplasia In Experimental Rabbit Vein Graft
Background: A recent clinical trial, PROactive, demonstrated that peroxisome proliferators-activated receptor γ ligand, pioglitazone improved cardiovascular outcome in patients with type II diabetes. Here, we investigated whether pioglitazone inhibits intimal hyperplasia seen in autologous vein grafts using an experimental rabbit vein graft model.
Methods: Male rabbits were randomly divided into two groups and were treated with or without pioglitazone as food admixture at a concentration of 0.01%. One week later, rabbits were subjected to jugular vein bypass grafting into carotid artery. The external jugular vein was interposed in the carotid artery in reversed fashion. At 28 days after surgery, intimal hyperplasia of the grafted vein was measured. Actively proliferating cells were identified using antibody to Ki−67. Apoptotic cells were evaluated by TUNEL-staining. Plasma levels of adiponectin, anti-atherogenic property were determined by Western blot analyses.
Results: There were no significant differences in body weight, blood pressure, heart rate, glucose and insulin levels between pioglitazone treated rabbit and non-treated rabbit. Treatment with pioglitazone markedly prevented intimal hyperplasia at 28 days after surgery in rabbit vein graft (n=7 in each group: p<0.01). Pioglitazone significantly decreased the number of Ki-67 positive proliferating cells in the neointima of the vein graft at 14 days after surgery (p<0.05). Pioglitazone also increased the number of TUNEL positive apoptotic cells in the neointima of the vein graft (p<0.05). Finally, treatment with pioglitazone led to a 1.6-fold increase in plasma adiponectin levels in rabbit.
Conclusions: Pioglitazone prevents intimal hyperplasia of rabbit autologous vein grafts by enhancing apoptosis and suppressing cell proliferation. This mechanism may be through the enhancement of adiponectin production, because plasm adiponectin was increased. Treatment with pioglitazone could be a useful therapy for preventing intimal hyperplasia of the vein graft after bypass grafting.
- © 2010 by American Heart Association, Inc.