Effects and mechanism of tissue-type plasminogen activator and plasminogenactivator 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 plasminoge n activator (tPA) increased significantly during SMC proliferation and migr ation in rabbit iliac artery injury model. In this experiment, the relation ship of tPA, PAI-1 and vascular SMC proliferation was studied in vitro usin g human aortic smooth muscle cells cultivated in normal lipid or high lipid serum. The expression of certain oncogenes during the SMC proliferation wa s detected by Northern blot. Results: tPA stimulates vascular SMC prolifera tion in a dose-dependent manner, and the effect is increased significantly in high lipid environment. PAI-1 inhibits the mitogenic effect of tPA to SM C and is dose-dependent, tPA increases oncogene c-myc mRNA level during SMC proliferation, and the level of c-myc mRNA increases significantly in hype rlipidemia. These findings indicate that tPA directly promotes human vascul ar SMC proliferation in vitro, and may contribute to intimal SMC proliferat ion after vascular injury by increasing the expression of oncogene c-myc mR NA. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.