Effect of endothelin on the regulation of the fibrinolytic system of cultured human vascular smooth muscle cells

Summary The effect of endothelin-1 (ET-1) and ET-3 on the fibrinolytic system of cultured human vascular smooth muscle cells (SMCs) was investigated. When confluent cultures of human aortic SMCs (HASMCs) and human basilaris artery SMCs (HBASMCs) were conditioned with ET-1 or ET-3 (0.1 to 100 nM) plasminogen activator inhibitor-1 (PAI-1) synthesis increased up to 135% (HASMCs) or 179% (HBASMCs) of control whereas tissue-type plasmingen activator (t-PA) synthesis decreased down to 70% of control in both types of SMCs. PAI-1 mRNA levels were upregulated to 200% of control levels and t-PA mRNA decreased by 50% when the cells were treated with 100 nM ET-1 or ET-3. We provide evidence for a new function of endothelins towards vascular smooth muscle cells. By decreasing the fibrinolytic potential of SMCs, endothelin might contribute to the development of thrombosis seen in cardiovascular diseases associated with vascular injury and/or smooth muscle cell activation such as atherosclerosis and myocardial infarction.