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Plasminogen Activator Inhibitor-1 Is a Marker and a Mediator of Senescence
Open accessAbstract
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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“SERPINE1 by itself is a marker of PS hepatocytes and is a known mediator of senescence.45”
From Cellular senescence in human liver under normal aging and cancer (2026) · cites this paper as [45]
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“We found that SERPINE1, a known senescence marker and SASP factor, was co-expressed with these genes in Module-5 [73].”
From Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics (2024) · cites this paper as [73]
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“SASP markers were elevated at the protein and gene levels in lung tissue from our COVID-19 autopsy case series, including PAI-1, which is considered both a major marker and mediator of cellular senescence (65).”
From Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19 (2021) · cites this paper as [65]
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Cites
Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818
Ghosh, A. K., & Vaughan, D. E. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22783 · Cited by 701
Self-citationKortlever, R. M., Higgins, P. J., & Bernards, R. (2006) · Nature Cell Biology · doi:10.1038/ncb1448 · Cited by 637 · cited 1×
“ing for the first time that PAI-1 is a marker and mediator of replicative senescence.(38) The authors concluded that regulation”
Eitzman, D. T., McCoy, R. D., Zheng, X., Fay, W. P., Shen, T., Ginsburg, D., & Simon, R. H. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118396 · Cited by 560
Fibrin Clot Structure and Function
Undas, A., & Ariëns, R. A. S. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.230631 · Cited by 549
Sirt1 modulates premature senescence-like phenotype in human endothelial cells
Ota, H., Akishita, M., Eto, M., Iijima, K., Kaneki, M., & Ouchi, Y. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.08.008 · Cited by 429
Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells.
Loskutoff, D. J., van MOURIK, J. A., Erickson, L. A., & Lawrence, D. A. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.10.2956 · Cited by 399
cDNA cloning of human plasminogen activator-inhibitor from endothelial cells.
Ginsburg, D., Zeheb, R., Yang, A. Y., Rafferty, U. M., Andreasen, P. A., Nielsen, L., Danø, K., Lebo, R. V., & GELEHRTER, T. D. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112761 · Cited by 346
Carmeliet, P., Kieckens, L., Schoonjans, L., Neugeboren, B. I., Nuffelen, A. V., Prendergast, G. C., Cole, M. D., Bronson, R. T., Collen, D., & Mulligan, R. C. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116892 · Cited by 345
Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior
Pawlak, R., Magariños, A. M., Melchor, J. P., McEwen, B. S., & Strickland, S. (2003) · Nature Neuroscience · doi:10.1038/nn998 · Cited by 305
Özcan, S., Alessio, N., Acar, M. B., Mert, E., Omerli, F., Peluso, G., & Galderisi, U. (2016) · Aging · doi:10.18632/aging.100971 · Cited by 295
Complete Deficiency of Plasminogen-Activator Inhibitor Type 1 Due to a Frame-Shift Mutation
Fay, W. P., Shapiro, A. D., Shih, J. L., Schleef, R. R., & Ginsburg, D. (1992) · New England Journal of Medicine · doi:10.1056/nejm199212103272406 · Cited by 269
Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene
Erickson, L. A., Fici, G. J., Lund, J. E., Boyle, T. P., Polites, H. G., & Marotti, K. R. (1990) · Nature · doi:10.1038/346074a0 · Cited by 266
Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo
Brown, N. J., Nakamura, S., Ma, L., Nakamura, I., Donnert, E., Freeman, M. L., Vaughan, D. E., & Fogo, A. B. (2000) · Kidney International · doi:10.1046/j.1523-1755.2000.00277.x · Cited by 254
Self-citationFay, W. P., Parker, A. C., Condrey, L. R., & Shapiro, A. D. (1997) · Blood · doi:10.1182/blood.v90.1.204 · Cited by 249
Piper, M. D. W., & Bartke, A. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.06.012 · Cited by 225
Pawlak, R., Rao, B. S. S., Melchor, J. P., Chattarji, S., McEwen, B., & Strickland, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509232102 · Cited by 223
Homocysteine accelerates endothelial cell senescence
Xu, D. L., Neville, R. F., & Finkel, T. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01278-3 · Cited by 207
Murano, S., Thweatt, R., Shmookler Reis, R. J., Jones, R. A., Moerman, E. J., & Goldstein, S. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.8.3905 · Cited by 199
PAI-1–regulated extracellular proteolysis governs senescence and survival in Klotho mice
Eren, M., Boe, A. E., Murphy, S. B., Place, A. T., Nagpal, V., Morales-Nebreda, L., Urich, D., Quaggin, S. E., Budinger, G. R. S., Mutlu, G. M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321942111 · Cited by 176
Self-citationEren, M., Painter, C., Atkinson, J. B., Declerck, P. J., & Vaughan, D. E. (2002) · Circulation · doi:10.1161/01.cir.0000023186.60090.fb · Cited by 170
Self-citationYamamoto, K., Takeshita, K., Shimokawa, T., Yi, H., Isobe, K., Loskutoff, D. J., & Saito, H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.022608799 · Cited by 163
Elzi, D. J., Lai, Y., Song, M., Hakala, K., Weintraub, S. T., & Shiio, Y. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120437109 · Cited by 154
Stress-induced spine loss in the medial amygdala is mediated by tissue-plasminogen activator
Bennur, S., Rao, B. S. S., Pawlak, R., Strickland, S., McEwen, B. S., & Chattarji, S. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.075 · Cited by 145
Rånby, M., Sundell, I. B., & Nilsson, T. (1989) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1651028 · Cited by 134
Boe, A. E., Eren, M., Murphy, S. B., Kamide, C., Ichimura, A., Terry, D. B., McAnally, D., Smith, L. H., Miyata, T., & Vaughan, D. E. (2013) · Circulation · doi:10.1161/circulationaha.113.003192 · Cited by 132
Self-citationFay, W. P., Parker, A. C., Condrey, L. R., et al. (1997) · Blood · doi:10.1182/blood.v90.1.204.204_204_208 · Cited by 114
Comi, P., Chiaramonte, R., & Maier, J. A. M. (1995) · Experimental Cell Research · doi:10.1006/excr.1995.1232 · Cited by 112
Dosne, A. M., Dupuy, É., & Bodevin, E. (1978) · Thrombosis Research · doi:10.1016/0049-3848(78)90309-2 · Cited by 107
Mamdani, F., Rollins, B. L., Morgan, L., Myers, R., Barchas, J. D., Schatzberg, A. F., Watson, S. J., Akil, H., Potkin, S. G., Bunney, W. E., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.134 · Cited by 99
A small molecule inhibitor of PAI-1 protects against doxorubicin-induced cellular senescence
Ghosh, A. K., Rai, R., Park, K. E., Eren, M., Miyata, T., Wilsbacher, L. D., & Vaughan, D. E. (2016) · Oncotarget · doi:10.18632/oncotarget.12494 · Cited by 95
Self-citationLIJNEN, H. R., Maquoi, E., Morange, P., Vörös, G., HOEF, B. V., Kopp, F., Collen, D., Juhan-Vague, I., & Alessi, M. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000044457.60665.dd · Cited by 94
Mamdani, F., Rollins, B. L., Morgan, L., Myers, R., Barchas, J. D., Schatzberg, A. F., Watson, S. J., Akil, H., Potkin, S. G., Bunney, W. E., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2015.164 · Cited by 78
NH4Cl Treatment Prevents Tissue Calcification in Klotho Deficiency
Leibrock, C. B., Alesutan, I., Voelkl, J. G. J., Pakladok, T., Michael, D., Schleicher, E. D., Kamyabi-Moghaddam, Z., Quintanilla‐Martínez, L., Kuro‐o, M., & Lang, F. J. W. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014030230 · Cited by 62
Goldstein, S., Moerman, E. J., Fujii, S., & Sobel, B. E. (1994) · Journal of Cellular Physiology · doi:10.1002/jcp.1041610321 · Cited by 59
Chen, H., Wan, Y.-Z., Zhou, S., Lu, Y., Zhang, Z., Zhang, R., Chen, F., Hao, D., Zhao, X., Guo, Z.-C., et al. (2012) · Science China Life Sciences · doi:10.1007/s11427-012-4329-4 · Cited by 58
Kortlever, R. M., Nijwening, J. H., & Bernards, R. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803341200 · Cited by 55
Age-Related Changes in Aortic Valve Hemostatic Protein Regulation
Balaoing, L. R., Post, A., Liu, H., Minn, K. T., & Grande-Allen, K. J. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.301936 · Cited by 53
Chung, E. J., McKay-Corkum, G. B., Chung, S. I., White, A. O., Scroggins, B. T., Mitchell, J. B., Mulligan‐Kehoe, M. J., & Citrin, D. E. (2015) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2015.11.044 · Cited by 46
Plasminogen Activator Inhibitor-1 in depression: Results from Animal and Clinical Studies
Jiang, H., Li, X., Chen, S., Lu, N., Yue, Y., Liang, J., Zhang, Z., & Yuan, Y. (2016) · Scientific Reports · doi:10.1038/srep30464 · Cited by 45
Aging is associated with impaired thrombus resolution in a mouse model of stasis induced thrombosis
McDonald, A. P., Meier, T. R., Hawley, A. E., Thibert, J. N., Farris, D. M., Wrobleski, S. K., Henke, P. K., Wakefield, T. W., & Myers, D. D. (2009) · Thrombosis Research · doi:10.1016/j.thromres.2009.06.005 · Cited by 44
Increased Monocytic Adhesion by Senescence in Human Umbilical Vein Endothelial Cells
Yanaka, M., Honma, T., Sato, K., Shinohara, N., Ito, J., Tanaka, Y., Tsuduki, T., & Ikeda, I. (2011) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.100909 · Cited by 39
Blood-based immune-endocrine biomarkers of treatment response in depression
Chan, M. K., Cooper, J. D., Bot, M., Birkenhäger, T. K., Bergink, V., Drexhage, H. A., Steiner, J. H., Rothermundt, M., Penninx, B. W. J. H., & Bahn, S. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.08.020 · Cited by 36
Nilsson, T., Sundell, I. B., Hellsten, G., & Hallmans, G. (1990) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.1990.tb00156.x · Cited by 35
αMUPA mice: a transgenic model for increased life span☆
Miskina, R., Masos, T., Yahav, S., Shinder, D., & Globerson, A. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00093-7 · Cited by 34
Kodaman, N. M., Aldrich, M. C., Sobota, R. S., Asselbergs, F. W., Brown, N. J., Moore, J. H., & Williams, S. M. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003867 · Cited by 26
Reactive site‐dependent phenotypic alterations in plasminogen activator inhibitor‐1 transgenic mice
Eren, M., Gleaves, L. A., Atkinson, J. B., King, L. E., Declerck, P. J., & Vaughan, D. E. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02587.x · Cited by 24
Self-citationSavoy, C. D., Lieshout, R. J. V., & Steiner, M. S. (2016) · Acta Physiologica · doi:10.1111/apha.12726 · Cited by 24
Tosur, Z., Green, D., De Chavez, P. J., Knutson, K. L., Goldberger, J. J., Zee, P., Liu, K., Kim, K.-Y., & Carnethon, M. R. (2014) · Sleep Medicine · doi:10.1016/j.sleep.2014.04.005 · Cited by 21
Górska-Ciebiada, M., Saryusz‐Wolska, M., Borkowska, A., Ciebiada, M., & Loba, J. M. (2015) · Aging Clinical and Experimental Research · doi:10.1007/s40520-015-0504-3 · Cited by 17
Transgenic overexpression of a stable Plasminogen Activator Inhibitor-1 variant
Fahim, A. T., Wang, H., Feng, J., & Ginsburg, D. (2008) · Thrombosis Research · doi:10.1016/j.thromres.2008.07.004 · Cited by 14
Nitric Oxide Prevents Alveolar Senescence and Emphysema in a Mouse Model
Boe, A. E., Eren, M., Morales‐Nebreda, L., Murphy, S. B., Budinger, G. R. S., Mutlu, G. M., Miyata, T., & Vaughan, D. E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0116504 · Cited by 13
Self-citationThe effects of whole body vibration and exercise on fibrinolysis in men
Boyle, L. J., & Nagelkirk, P. R. (2010) · European Journal of Applied Physiology · doi:10.1007/s00421-010-1590-8 · Cited by 9
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Metadata
- Authors
- Vaughan, D. E., Rai, R., Khan, S. S., Eren, M., & Ghosh, A. K.
- Affiliations
- Northwestern University (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2017-08
- Volume
- 37
- Issue
- 8
- Pages
- 1446-1452
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC5846199
- OpenAlex
- W2621285299
- Cited by
- 258
- References
- 52
- Citations by year
- 2026: 33 · 2025: 27 · 2024: 35 · 2023: 27 · 2022: 34 · 2021: 34 · 2020: 29 · 2019: 24 · 2018: 14
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1p01hl108795-01)
- National Heart, Lung, and Blood Institute (P01-HL-108795, R01HL051387, F32HL129695)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- plasminogen activator inhibitor-1, cellular senescence, aging, accelerated aging, serine protease inhibitors, plasminogen activator, biomarkers, multimorbidity
- MeSH terms
- Aging, Animals, Disease, Health Status, Humans, Signal Transduction, Biomarkers, Cellular Senescence, Plasminogen Activator Inhibitor 1
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