J Korean Diabetes Assoc.  2000 Jun;24(3):348-355.

The Effects of Troglitazone on Vascular Smooth Muscle Cell Proliferation

• Chung YJ
• Min KM
• Oh EY
• Chung JH
• Min YK
• Lee MS
• Lee MK
• Kim KW

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.

Keyword

PPAR; Vascular smooth muscle cell proliferation; Atherosclerosis; Insulin

MeSH Terms

Animals
Atherosclerosis
Cardiovascular Diseases
Cell Proliferation*
Diabetes Mellitus, Type 2
DNA
Fasting
Humans
Hypertension
Insulin
Insulin-Like Growth Factor I
Muscle, Smooth
Muscle, Smooth, Vascular*
Myocytes, Smooth Muscle
Obesity
Peroxisome Proliferator-Activated Receptors
Peroxisomes
PPAR gamma
Rats
Rats, Sprague-Dawley
Risk Factors
RNA, Messenger
DNA
Insulin
Insulin-Like Growth Factor I
PPAR gamma
Peroxisome Proliferator-Activated Receptors
RNA, Messenger