Effects of thiazolidinediones on growth and differentiation of human aorta and coronary myocytes.
Thiazolidinediones, insulin-sensitizing agents that lower insulin and lipid levels in insulin-resistant states, block agonist-induced Ca2+ entry into vascular smooth muscle (VSM) cells in vitro and lower blood pressure in animals and humans in vivo. In this study, we investigated the effects of ciglitazone and troglitazone on cell growth and DNA synthesis (as thymidine incorporation), and differentiation in cultured human aorta (haVSM) and human coronary artery (hcaVSM) VSM cells. Mitotically quiescent haVSM cells were stimulated with serum or platelet-derived growth factor (PDGF). Ciglitazone (40 micromol/L) inhibited haVSM cell proliferation by 84 +/- 16% (mean +/- SEM) (P < .05, n = 3), and serum and PDGF stimulated [3H]-thymidine incorporation by 91 +/- 18% (P < .03, n = 3) and 73 +/- 14% (P < .03, n = 4), respectively. Troglitazone (5 micromol/L) inhibited proliferation of haVSM cells by 78 +/- 14% (P < .05, n = 3) and hcaVSM cells by 91 +/- 18% (P < .05, n = 3). Proliferating VSM cells (synthetic phenotype) expressed small amounts of alpha-actin, whereas nonproliferating VSM cells (contractile phenotype) exhibited abundant alpha-actin. Exposure of proliferating haVSM cells to 40 micromol/L ciglitazone induced a marked increase in alpha-actin staining, consistent with transition to the well differentiated, contractile phenotype. To the extent that thiazolidinediones similarly affect growth factor-induced proliferation and differentiation of arterial myocytes in vivo, these agents may be useful in treating atherosclerosis and in preventing restenosis after angioplasty.
Morikang
E
E
Department of Biological Sciences, California State University, Hayward, USA.
Benson
S C
SC
Kurtz
T W
TW
Pershadsingh
H A
HA
D001011:Aorta / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D003331:Coronary Vessels / Q000473:pathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone; C039671:ciglitazone