PLASMINOGEN DEFICIENCY ACCELERATES VESSEL WALL DISEASE IN MICE PREDISPOSED TO ATHEROSCLEROSIS

A critical link between hemostatic factors and atherosclerosis has bee n inferred from a variety of indirect observations, including the expr ession of procoagulant and fibrinolytic factors within atherosclerotic vessels, the presence of fibrin in intimal lesions, and the cellular infiltration of mural thrombi leading to their incorporation into deve loping plaques. To directly examine the role of the key fibrinolytic f actor, plasminogen, in atherogenesis, plasminogen-deficient mice were crossed to hypercholesterolemic, apolipoprotein E-deficient mice predi sposed to atherosclerosis, We report that the loss of plasminogen grea tly accelerates the formation of intimal lesions in apolipoprotein E-d eficient animals, whereas plasminogen deficiency alone does not cause appreciable atherosclerosis. These studies provide direct evidence tha t circulating hemostatic factors strongly influence vessel wall diseas e in the context of a disorder in lipid metabolism.