Effects and mechanism of tissue-type plasminogen activator and plasminogen activator inhibitor on vascular smooth muscle cell proliferation

Smooth muscle cell (SMC) proliferation and migration play a pivotal role in restenosis following angioplasty. The expression of tissue-type plasminogen activator (tPA) increased significantly during SMC proliferation and migration in rabbit iliac artery injury model. In this experiment, the relationship of tPA, PAI-1 and vascular SMC proliferation was studied in vitro using human aortic smooth muscle cells cultivated in normal lipid or high lipid serum. The expression of certain oncogenes during the SMC proliferation was detected by Northern blot. Results: tPA stimulates vascular SMC proliferation in a dose-dependent manner, and the effect is increased significantly in high lipid environment. PAI-1 inhibits the mitogenic effect of tPA to SMC and is dose-dependent. tPA increases oncogene c-myc mRNA level during SMC proliferation, and the level of c-myc mRNA increases significantly in hyperlipidemia. These findings indicate that tPA directly promotes human vascular SMC proliferation in vitro, and may contribute to intimal SMC proliferation after vascular injury by increasing the expression of oncogene c-myc mRNA.