FIBRINOGEN DEFICIENCY IS COMPATIBLE WITH THE DEVELOPMENT OF ATHEROSCLEROSIS IN MICE

A critical role of the coagulation system in the development of athero sclerosis has been frequently postulated based on a variety of indirec t observations, including the expression of procoagulants and fibrinol ytic factors within atherosclerotic vessels, the presence of substanti al amounts of fibrin(ogen) and fibrin degradation products within inti mal lesions, the cellular infiltration and assimilation of mural throm bi Into developing plaques, and the identification of high plasma fibr inogen (Fib) levels as an independent risk factor for the development of ischemic heart disease, To directly examine the role of fibrin(ogen ) in atherogenesis, Fib-deficient mice were crossed to atherosclerosis -prone apolipoprotein E (apo E)-deficient mice. Both apo E-/- and apo E-/-/Fib(-/-) mice developed lesions throughout the entire aortic tree , ranging in appearance from simple fatty streaks to complex fibrous p laques, Furthermore, remarkably little difference in lesion size and c omplexity was observed within the aortae of age- and gender-matched ap o E-/- and apo E-/-/Fib(-/-) mice. These results indicate that the con tribution of fibrin(ogen) to intimal mass and focal cell adhesion, mig ration, and proliferation is not strictly required for the development of advanced atherosclerotic disease in mice with a severe defect in l ipid metabolism.