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Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk
Open accessAbstract
Elevated plasma plasminogen activator inhibitor-1 (PAI-1) level is a core feature of insulin-resistance syndrome (IRS). Atherothrombotic complications in IRS are partly attributed to impaired fibrinolysis caused by increased plasma PAI-1 levels. Although the etiology of IRS is far from being explained, the clustering of inflammation, adipose tissue accumulation and insulin resistance suggests an etiopathological link. Proinflammatory cytokines might regulate PAI-1 expression in IRS; however, more studies are needed to confirm this complex mechanism in humans. Furthermore, modifying PAI-1 expression by PAI-1 inhibitors provides a new challenge and may reveal the true role of PAI-1 in atherosclerotic and insulin resistance processes.
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“Postprandial hyperglycaemia is also correlated with impaired myocardial perfusion in diabetic patients (658) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [658]
In the citing paper
“These include increased production of inflammatory cytokines, 35,36 plasminogen activator inhibitor-1, 37 and other bioactive products 38 -40 ; at the same time the potentially protective adipokine, adiponectin, is reduced.41,42”
From Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (2005) · cites this paper as [37]
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Sahu, B., & Bal, N. C. (2022) · Biochimie · doi:10.1016/j.biochi.2022.09.003 · Cited by 73
Nagy, B., Fülöp, T., Varga, Z., Karányi, Z., Magyar, M. T., Oláh, L., Papp, M., Facskó, A., Kappelmayer, J., Paragh, G., et al. (2011) · Thrombosis and Haemostasis · doi:10.1160/th11-01-0030 · Cited by 62
“Elevated PAI-1 antigen level was measured in patients with impaired glucose tolerance (46) and considered as a biochemical feature of insulin resistance syndrome (47).”
BackgroundAdipose Tissue and Atherothrombosis
Alessi, M., LIJNEN, H. R., Bastelica, D., & Juhan-Vague, I. (2003) · Pathophysiology of Haemostasis and Thrombosis · doi:10.1159/000083816 · Cited by 62
Self-citationEl-Baz, F. K., Aly, H. F., & Abd-Alla, H. I. (2019) · Toxicology Reports · doi:10.1016/j.toxrep.2019.12.008 · Cited by 62
Adipose Tissue and Ceramide Biosynthesis in the Pathogenesis of Obesity
Samad, F., Badeanlou, L., Shah, C., & Yang, G. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0650-1_5 · Cited by 61
Mastinu, A., Premoli, M., Ferrari‐Toninelli, G., Tambaro, S., Maccarinelli, G., Memo, M., & Bonini, S. A. (2018) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2018-0013 · Cited by 62
Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity
Darmon, P., Dadoun, F., Boullu-Ciocca, S., Grino, M., Alessi, M.-C., & Dutour, A. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00654.2005 · Cited by 59
“Elevated plasma levels of PAI-1 have been found in patients with obesity, insulin resistance, and cardiovascular diseases (23, 48); moreover, PAI-1 excess has been shown to induce insulin resistance in adipocytes (27).”
BackgroundSelf-citationKwon, E., Lee, J., Kim, Y.-S., Do, A., Choi, J., Cho, S.-J., Jung, U. J., Lee, M., Park, Y., & Choi, M. (2017) · Nutrients · doi:10.3390/nu9060569 · Cited by 59
“In addition, IL-6 and PAI-1 are also pro-inflammatory cytokines synthesized by adipocyte, and its levels in plasma are increased in obesity and insulin resistance [42,43].”
Backgroundde la Monte, S. M., Tong, M., Daiello, L. A., & Ott, B. R. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180906 · Cited by 63
Growth hormone, menopause and ageing: no definite evidence for 'rejuvenation' with growth hormone
Fanciulli, G., Delitala, A., & Delitala, G. (2009) · Human Reproduction Update · doi:10.1093/humupd/dmp005 · Cited by 56
Markers of Hemostasis and Systemic Inflammation in Heart Disease and Atherosclerosis in Smokers
MacCallum, P. K. (2005) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200406-036ms · Cited by 55
Metaflammatory responses during obesity: Pathomechanism and treatment
Debnath, M., Agrawal, S., Agrawal, A., & Dubey, G. P. (2015) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2015.10.012 · Cited by 58
“Increase in visceral fat mass results in eleation of circulating inflammatory mediators like -reactive protein, acute phase inflammatory proein and pro-inflammatory cytokines like adhesion nd remodelling molecule [94—96].”
BackgroundAdipokines and Cardiovascular Risk in Cushing’s Syndrome
Valassi, E., Biller, B. M. K., Klibanski, A., & Misra, M. (2011) · Neuroendocrinology · doi:10.1159/000330416 · Cited by 54
Al-Hamodi, Z. H., Ismail, I. S., Saif-Ali, R., Ahmed, K. A., & Muniandy, S. (2011) · Cardiovascular Diabetology · doi:10.1186/1475-2840-10-23 · Cited by 54
“The circulating PAI-1 levels are positively associated with obesity and insulin resistance [28-30].”
BackgroundPosterior Reversible Encephalopathy Syndrome After Transplantation: a Review
Chen, S., Hu, J., Xu, L., Brandon, D., Yu, J., & Zhang, J. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9560-0 · Cited by 52
“Previous research also reported that the inducers of PAI-1 involve the product of proinflammatory mediators, such as tumor necrosis factor-α and interleukin-1 [93, 94].”
BackgroundFang, C., Kim, H., Barnes, R. C., Talcott, S. T., & Mertens‐Talcott, S. U. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800129 · Cited by 53
Metabolic Syndrome: The Constellation of Co-morbidities, A Global Threat
Madan, K., Paliwal, S., Sharma, S. K., Kesar, S., Chauhan, N., & Madan, M. (2023) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530323666230309144825 · Cited by 55
Valle, M., Martos, R., Cañete, M. D., Valle, R., van Donkelaar, E. L., Bermudo, F., & Cañete, R. (2014) · Pediatric Diabetes · doi:10.1111/pedi.12199 · Cited by 49
The Ternary Complex Factor Net Regulates Cell Migration through Inhibition of PAI-1 Expression
Buchwalter, G., Gross, C., & Wasylyk, B. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10853-10862.2005 · Cited by 48
Plasminogen activator inhibitor 1 (PAI‐1): in vitro activities and clinical relevance
Horrevoets, A. J. G. (2004) · British Journal of Haematology · doi:10.1111/j.1365-2141.2004.04844.x · Cited by 48
Plasminogen Activator Inhibitor-1 in Obstructive Sleep Apnea Patients with and without Hypertension
Zamarrón, C., Ricoy, J., Riveiro, A., & Gudé, F. (2008) · Lung · doi:10.1007/s00408-008-9076-8 · Cited by 45
“Increased fibrinogen blood levels and decreased fibrinolytic activity associated with elevated concentrations of PAI-1 increase the risk of thrombosis and atherosclerosis in these patients [34].”
Background
Metadata
- Authors
- Juhan-Vague, I., Alessi, M.-C., Mavri, A., & Morange, P. E.
- Affiliations
- Inserm (FR)
- Corresponding author
- Juhan-Vague, I.
- Venue
- Journal of Thrombosis and Haemostasis
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 1
- Issue
- 7
- Pages
- 1575-1579
- ISSN
- 1538-7836 (ISSN-L)
- OpenAlex
- W2042742088
- Cited by
- 371
- References
- 95
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 13 · 2023: 8 · 2022: 14 · 2021: 6 · 2020: 11 · 2019: 14 · 2018: 10 · 2017: 17 · 2016: 9 · 2015: 19 · 2014: 14 · 2013: 11 · 2012: 13
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- plasminogen activator inhibitor-1, metabolic syndrome, inflammation, obesity, adipose tissue, inflammatory cytokines, impaired fibrinolysis, atherothrombosis, vascular risk, PAI-1 inhibitors, atherosclerosis
- MeSH terms
- Animals, Heart Diseases, Humans, Insulin Resistance, Obesity, Risk, Plasminogen Activator Inhibitor 1
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