Introduction: Thiazolidinedione (TZD) is widely used a drug for the treatment of type 2 diabetes and protects against cardiovascular events in human. However, it is not clear whether TZD can directly inhibit the progression of atherosclerosis. To test the hypothesis whether administration of TZD could reduce the development of atherosclerosis, we studied the effects of rosiglitazone on aortic atherosclerosis of rabbits fed a cholesterol diet.
Materials and methods: Male Japanese White rabbits were fed a diet containing either 0.3% cholesterol diet (control group, n=10) or 0.3% cholesterol with rosiglitazone (TZD-treated group, n=12) for 16 weeks. We compared the plasma lipids and the extent of aortic atherosclerosis between two groups.
Results and conclusions: TZD treatment significantly resulted in the reduction of aortic atherosclerosis by 21% in the aortic arch (p<0.01), 20% in the thoracic aorta (p=0.14), and 28% in the abdominal aorta (p=0.25), without affecting the plasma levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, glucose and insulin. Immunohistochemical staining showed that the cellular components (macrophages and smooth muscle cells) of the lesions of TZD-treated rabbits were unchanged compared to those of control rabbits. In addition, TZD treatment also led to dramatic improvement of fatty liver in cholesterol-fed rabbits. Our results suggest that the activation of PPARgamma can be beneficial for the treatment of atherosclerosis and fatty liver independent upon the improvement of plasma lipids and glucose metabolism.