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Hypofibrinolysis and increased PAI-1 are linked to atherothrombosis via insulin resistance and obesity.
Ann Med 2000; 32 Suppl 1:78-84AM

Abstract

Plasminogen activator inhibitor 1 (PAI-1) is the primary physiological inhibitor of plasminogen activation in vivo. Circulating PAI-1 levels are elevated in patients with coronary heart disease and may play an important role in the development of atherothrombosis by decreasing fibrin degradation. Increased PAI-1 expression can also directly influence vessel wall remodelling. Prospective cohort studies have underlined the association between increased plasma PAI-1 levels and the risk of coronary events, but the predictive capacity of PAI-1 disappeared after adjustments for insulin resistance markers. The insulin resistance syndrome, which is characterized partly by obesity with visceral fat accumulation, is considered as a major regulator of PAI-1 expression. Recently, production of PAI-1 by adipose tissue, in particular by fat from omentum, has been evidenced, and it has been proposed that it could be responsible for the elevated plasma PAI-1 level observed in insulin resistance. The role of stroma cells, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta as possible enhancers of PAI-1 synthesis are presently emphasized. Glucocorticoids and insulin may also be implicated. Moreover, a weak genetic control of plasma PAI-1 concentration has been described in patients with high plasma levels of PAI-1. The role of PAI-1 in the development of adipose tissue metabolism is important to consider as PAI-1 -/- mice submitted to a high-fat diet showed changes in cell composition of adipose tissue and in plasma insulin and triglyceride levels.

Authors+Show Affiliations

Laboratory of Hematology, Faculty of Medicine, CHU Timone, Marseille, France. ijuhan@mail.ap-hm.frNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

11209987

Citation

Juhan-Vague, I, et al. "Hypofibrinolysis and Increased PAI-1 Are Linked to Atherothrombosis Via Insulin Resistance and Obesity." Annals of Medicine, vol. 32 Suppl 1, 2000, pp. 78-84.
Juhan-Vague I, Alessi MC, Morange PE. Hypofibrinolysis and increased PAI-1 are linked to atherothrombosis via insulin resistance and obesity. Ann Med. 2000;32 Suppl 1:78-84.
Juhan-Vague, I., Alessi, M. C., & Morange, P. E. (2000). Hypofibrinolysis and increased PAI-1 are linked to atherothrombosis via insulin resistance and obesity. Annals of Medicine, 32 Suppl 1, pp. 78-84.
Juhan-Vague I, Alessi MC, Morange PE. Hypofibrinolysis and Increased PAI-1 Are Linked to Atherothrombosis Via Insulin Resistance and Obesity. Ann Med. 2000;32 Suppl 1:78-84. PubMed PMID: 11209987.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypofibrinolysis and increased PAI-1 are linked to atherothrombosis via insulin resistance and obesity. AU - Juhan-Vague,I, AU - Alessi,M C, AU - Morange,P E, PY - 2001/2/24/pubmed PY - 2001/4/6/medline PY - 2001/2/24/entrez SP - 78 EP - 84 JF - Annals of medicine JO - Ann. Med. VL - 32 Suppl 1 N2 - Plasminogen activator inhibitor 1 (PAI-1) is the primary physiological inhibitor of plasminogen activation in vivo. Circulating PAI-1 levels are elevated in patients with coronary heart disease and may play an important role in the development of atherothrombosis by decreasing fibrin degradation. Increased PAI-1 expression can also directly influence vessel wall remodelling. Prospective cohort studies have underlined the association between increased plasma PAI-1 levels and the risk of coronary events, but the predictive capacity of PAI-1 disappeared after adjustments for insulin resistance markers. The insulin resistance syndrome, which is characterized partly by obesity with visceral fat accumulation, is considered as a major regulator of PAI-1 expression. Recently, production of PAI-1 by adipose tissue, in particular by fat from omentum, has been evidenced, and it has been proposed that it could be responsible for the elevated plasma PAI-1 level observed in insulin resistance. The role of stroma cells, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta as possible enhancers of PAI-1 synthesis are presently emphasized. Glucocorticoids and insulin may also be implicated. Moreover, a weak genetic control of plasma PAI-1 concentration has been described in patients with high plasma levels of PAI-1. The role of PAI-1 in the development of adipose tissue metabolism is important to consider as PAI-1 -/- mice submitted to a high-fat diet showed changes in cell composition of adipose tissue and in plasma insulin and triglyceride levels. SN - 0785-3890 UR - https://www.unboundmedicine.com/medline/citation/11209987/Hypofibrinolysis_and_increased_PAI_1_are_linked_to_atherothrombosis_via_insulin_resistance_and_obesity_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11209987.ui DB - PRIME DP - Unbound Medicine ER -