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PMID: 9486990 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Fibrinogen deficiency is compatible with the development of atherosclerosis in mice.

The Journal of clinical investigation ·Vol. 101 ·No. 5 ·1998-03-01 ·Pages 1184-94

Xiao Q, Danton MJ, Witte DP, Kowala MC, Valentine MT, Degen JL

Abstract

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.

MeSH Terms
Afibrinogenemia/complications Alleles Animals Aorta/pathology Apolipoproteins E/genetics Arteriosclerosis/genetics,metabolism,pathology Fibrin/metabolism,physiology Fibrin Fibrinogen Degradation Products/metabolism Fibrinogen/genetics,metabolism Immunohistochemistry Mice Mice, Inbred C57BL Mice, Mutant Strains Muscle, Smooth/cytology Polymerase Chain Reaction
Chemicals
Apolipoproteins E Fibrin Fibrinogen Degradation Products Fibrin Fibrinogen
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Xiao Q
Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
Danton M J
Witte D P
Kowala M C
Valentine M T
Degen J L
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI1461
Published
1998-03-01
Pages
1184-94
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508671
Subset
IM
Grants
NHLBI NIH HHS · HL47826 · United States
External Links
PubMed source DOI: 10.1172/JCI1461 PMC Full Text View journal details
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