Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 37, Issue 8, Pages 1446-1452Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.117.309451
Keywords
aging; arteriosclerosis; endothelial dysfunction; plasminogen activator inhibitor-1; thrombosis; transforming growth factor-beta
Categories
Funding
- National Institutes of Health-National Heart, Lung, Blood Institute [5R01HL051387-19, 1P01HL108795, F32HL129695]
- American Heart Association [16GRNT31130010]
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PAI-1 (plasminogen activator inhibitor-1) is a member of the evolutionarily conserved serine protease inhibitor family and a potent and rapid-acting inhibitor of both of the mammalian plasminogen activators. Organismal homeostasis requires physiological levels of endogenous PAI-1, and increased PAI-1 production guides the onset and progression of numerous human diseases and contributes to the multimorbidity of aging. Both chronological and stress-induced accelerated aging are associated with cellular senescence and accompanied by marked increases in PAI-1 expression in tissues. Recent studies suggest that PAI-1 is not only a marker but also a key mediator of cellular senescence and organismal aging. Here, we review the significance of PAI-1 as a bonafide marker, as well as a critical mediator, of cellular senescence associated with aging and aging-related pathologies.
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