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+ e ntry 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 sy nthesis (as thymidine incorporation), and differentiation in cultured human aorta (haVSM) and human coronary artery (hcaVSM) VSM cells. Mito tically quiescent haVSM cells were stimulated with serum or platelet-d erived growth factor (PDGF). Ciglitazone (40 mu mol/L) inhibited haVSM cell proliferation by 84 +/- 16% (mean +/- SEM) (P <.05, n = 3), and serum and PDGF stimulated [H-3]-thymidine incorporation by 91 +/- 18% (P <.03, n = 3) and 73 +/- 14% (P <.03, n = 4), respectively. Troglita zone (5 mu mol/L) inhibited proliferation of haVSM cells by 78 +/- 14% (P <.05, n = 3) and hcaVSM cells by 91 +/- 18% (P <.05, n = 3). Proli ferating VSM cells (synthetic phenotype) expressed small amounts of a- actin, whereas nonproliferating VSM cells (contractile phenotype) exhi bited abundant alpha-actin. Exposure of proliferating haVSM cells to 4 0 mu mol/L ciglitazone induced a marked increase in alpha-actin staini ng, consistent with transition to the well differentiated, contractile phenotype. To the extent that thiazolidinediones similarly affect gro wth factor-induced proliferation and differentiation of arterial myocy tes in vivo, these agents may be useful in treating atherosclerosis an d in preventing restenosis after angioplasty. (C) 1997 American Journa l of Hypertension, Ltd.