Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 22, Issue 3, Pages 499-505Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/hq0302.104529
Keywords
plasminogen activator inhibitor-1; atherosclerosis; collagen; matrix; transforming growth factor-beta 1
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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.
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