Characterization of an inhibitory effect of pioglitazone on balloon-injured vascular smooth muscle cell growth.
This study investigates whether pioglitazone could suppress an atherogenic process such as balloon-injured carotid intimal thickening and the proliferation of vascular smooth muscle cells (VSMC). We first examined the effect of pioglitazone to determine whether it could suppress intimal thickening induced by balloon catheterization in Sprague-Dawley rats. After 14 days postcatheterization in the left common carotid artery, the neointimal layers were completely occupied by proliferated VSMC, and the area ratio of neointima to media treated with 10 mg/kg/d of pioglitazone was significantly decreased to 57%. Next, we evaluated the effect of pioglitazone on the proliferation of rat cultured VSMC. Piogliotazone dose-dependently decreased the values of DNA synthesis, total cellular protein content, phosphorylations of extracellular signal-regulated protein kinase 1/2 and mitogen-activated protein kinase kinase 1/2, and proliferative cell nuclear antigen in VSMC. Pioglitazone also inhibited the phosphorylation of Pyk2. We conclude that pioglitazone itself could be effective for suppressing the growth of VSMC and consequent carotid intimal thickening.
Igarashi
M
M
Third Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.
Hirata
A
A
Yamaguchi
H
H
Tsuchiya
H
H
Ohnuma
H
H
Tominaga
M
M
Daimon
M
M
Kato
T
T
D000818:Animals; D001835:Body Weight; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004261:DNA Replication; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
D009687:Nuclear Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D020928:Mitogen-Activated Protein Kinases; D000077205:Pioglitazone