Abstract

BACKGROUND
Elevated fasting and postprandial insulin levels are frequently observed in patients with obesity and hypertension as well as type 2 diabetes mellitus. This phenomenon has been suggested as an independent risk factors for atherosclerotic cardiovascular diseases. Troglitazone, an insulin-sensitizing antidiabetic agent, has been shown to inhibit atherosclerotic process, but its mechanism of action is not yet elucidated. This study was undertaken to examine the effects of troglitazone, a peroxisome proliferator- activated receptor- (PPAR ) ligand, on vascular smooth muscle cell proliferation. METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats and the effects of several different agonists (insulin, ET-I, IGF-I) on cellular DNA synthesis were measured and compared with the effects of troglitazone. In addition, the mRNA of PPARgamma gene in rat aortic smooth muscle cells(RASMCs) was detected by RT-PCR methods. RESULTS:1. Insulin, endothelin-I and IGF-I significantly stimulated DNA synthesis in RASMCs (p<0.05). 2. Insulin-induced DNA synthesis was not significantly inhibited by coincubation with wortmannin or LY294002 but inhibited by PD98059. 3. Troglitazone significantly inhibited insulin, endothelin-I and IGF-I-induced DNA synthesis in RASMCs (p<0.05, respectively). 4. PPAR mRNA was detected in RASMCs by RT-PCR and its expression did not significantly increase by troglitazone treatment. CONCLUSION: Troglitazone could inhibit agonist-induced proliferation of vascular smooth muscle cells and might be a useful agent for treatment as well as prevention of atherosclerosis.

• Keywords: PPAR;Vascular smooth muscle cell proliferation;Atherosclerosis;Insulin