Abstract
Epidemiological studies suggest that elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) predispose an individual to ischemic heart disease or promote plaque progression by inhibiting fibrinolysis. In the present study, loss of PAI-1 in apolipoprotein E (apoE)-deficient (apoE(-/-):PAI-1(-/-)) mice promoted the growth of advanced atherosclerotic plaques, which was due to enhanced extracellular matrix deposition. ApoE(-/-):PAI-1(-/-) plaques also exhibited collagen fiber disorganization and degradation. Immunostaining and bone marrow transplantation revealed that smooth muscle cells, not macrophages, primarily expressed PAI-1 in plaques. Thus, although PAI-1 may promote plaque growth because of its antifibrinolytic properties, the present study reveals a protective role for PAI-1 by limiting plaque growth and preventing abnormal matrix remodeling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apolipoproteins E / genetics*
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Arteriosclerosis / etiology*
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Arteriosclerosis / metabolism
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Arteriosclerosis / pathology
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Bone Marrow Transplantation
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Cells, Cultured
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Cholesterol / blood
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Collagen / metabolism
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Collagen / ultrastructure
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Disease Progression
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Extracellular Matrix / metabolism*
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Extracellular Matrix / ultrastructure
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Fibrinolysin / biosynthesis
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Fibrinolysis
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Fibroblasts / metabolism
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Macrophages / metabolism
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Mice
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Mice, Knockout
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Myocardium / cytology
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Plasminogen Activator Inhibitor 1 / genetics
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Plasminogen Activator Inhibitor 1 / physiology*
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Transforming Growth Factor beta / metabolism
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Transforming Growth Factor beta1
Substances
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Apolipoproteins E
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Plasminogen Activator Inhibitor 1
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Tgfb1 protein, mouse
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Collagen
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Cholesterol
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Fibrinolysin