Fibrinogen deficiency is compatible with the development of atherosclerosis in mice.
A critical role of the coagulation system in the development of atherosclerosis has been frequently postulated based on a variety of indirect observations, including the expression of procoagulants and fibrinolytic factors within atherosclerotic vessels, the presence of substantial amounts of fibrin(ogen) and fibrin degradation products within intimal lesions, the cellular infiltration and assimilation of mural thrombi into developing plaques, and the identification of high plasma fibrinogen (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 plaques. Furthermore, remarkably little difference in lesion size and complexity was observed within the aortae of age- and gender-matched apo E-/- and apo E-/-/Fib-/- mice. These results indicate that the contribution of fibrin(ogen) to intimal mass and local cell adhesion, migration, and proliferation is not strictly required for the development of advanced atherosclerotic disease in mice with a severe defect in lipid metabolism.
Xiao
Q
Q
Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
Danton
M J
MJ
Witte
D P
DP
Kowala
M C
MC
Valentine
M T
MT
Degen
J L
JL
D000347:Afibrinogenemia / Q000150:complications*; D000483:Alleles; D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005337:Fibrin / Q000378:metabolism / Q000502:physiology; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009130:Muscle, Smooth / Q000166:cytology; D016133:Polymerase Chain Reaction
D001057:Apolipoproteins E; D005338:Fibrin Fibrinogen Degradation Products; D005337:Fibrin; D005340:Fibrinogen