Effect of tissue plasminogen activator on vascular smooth muscle cells

TPA has been clinically used as a thrombolytic agent in the treatment of acute thrombotic disorders. Transferring the tPA gene into vascular cells as a strategy of gene therapy has been proposed to enhance fibrinolytic capability and therefore inhibit thrombosis and restenosis after vascular interventions. The mechanism(s) by which tPA affects SMC proliferation and vascular remodeling has not been thoroughly characterized. This study unveils the relationship between thrombolytic activity and intimal hyperplasia by showing how the elevated expression of tPA affects the vascular remodeling. This study underscores that the overexpression of an enzyme thought beneficial to blood flow can potentially compromise blood flow by altering the biology of the cell engineered to express it. The results are important to the rational engineering of bioactive grafts with better patency. A new strategy to enhance the thrombolytic ability of a vascular surface without inducing excessive neointimal hyperplasia is proposed.