Fibrinolytic function and coronary risk

被引：29

作者：

Juhan-Vague I. ^{[1
]}

Morange P. ^{[1
]}

Alessi M.C. ^{[1
]}

机构：

[1] Laboratoire d'Hématologie, CHU Timone

来源：

Current Cardiology Reports | 1999年 / 1卷 / 2期

关键词：

Arterioscler Thromb Vasc Biol; Human Adipose Tissue; Plasminogen Activator Inhibitor Type; Activator Mass Concentration; Endogenous Fibrinolysis;

D O I：

10.1007/s11886-999-0069-x

中图分类号：

学科分类号：

摘要：

Plasminogen activation potential in the blood is controlled by an equilibrium between plasminogen activators, mainly tissue-type plasminogen activator (t-PA), and inhibitors, mainly plasminogen activator inhibitor (PAI)-1. In cardiovascular practice, imbalance of this fibrinolytic potential is encountered primarily in the insulin-resistance syndrome. This syndrome leads to increased plasma PAI-1 and t-PA antigen levels (reflecting inactive t-PA/PAI-1 complexes) with a consequent decrease in fibrinolytic activity. Increased plasma PAI-1 and t-PA antigen both are predictive of myocardial infarction. The prognostic value of PAI-1 disappears after adjustments for insulin resistance markers, whereas the prognostic value of t-PA antigen disappears after simultaneous adjustments for insulin resistance and inflammation markers, suggesting an additive role of inflammation in inducing plasma fibrinolytic markers. Recently the production of PAI-1 by adipose tissue, in particular by tissue from the omentum, has been shown. PAI-1 produced in this way could be an important contributor to the elevated plasma PAI-1 levels observed in insulin-resistant patients. These results support the notion that PAI-1 may be a link between obesity, insulin resistance, and cardiovascular disease. Genetic control of PAI-1 expression has also been shown, involving a - 675 4G/5G polymorphism, the 4G/4G genotype being associated with higher plasma PAI-1 levels; its proper influence on the development of myocardial infarction is still debated. Copyright © 1999 by Current Science Inc.

引用

页码：119 / 124

页数：5

共 70 条

[61]

Ossei-Gerning N., Mansfield M.W., Stickland M.H., Et al., Plasminogen activator inhibitor 1 promoter 4G/5G genotype and plasma levels in relation to a history of myocardial infarction in patients characterized by coronary angiography, Arterioscler Thromb Vasc Biol, 17, pp. 33-37, (1997)

[62]

Burzotta F., Di Castelnuovo A., Amore C., Et al., 4G/5G promoter PAI-1 gene polymorphism is associated with plasmatic PAI 1 activity in Italians: A model of gene environment interaction, Thromb Haemost, 79, pp. 354-358, (1998)

[63]

Ridker P.M., Hennekens C.H., Lindpaintner K., Et al., Arterial and venous thrombosis is not associated with the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor gene in a large cohort of US men, Circulation., 95, pp. 59-62, (1997)

[64]

Burzotta F., Di Castelnuovo A., Amore C., Et al., 4G/5G polymorphism in the promoter region of the PAI-1 gene is not a risk factor for familial myocardial infarction: A case control study in a sample of GISSI 2 patients, Thromb Haemost, 78, pp. 1294-1295, (1997)

[65]

Margaglione M., Cappucci G., Colaizzo D., Et al., The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease, Arterioscler Thromb Vasc Biol, 18, pp. 152-156, (1998)

[66]

Iacovello L., Burzotta F., Di Castelnuovo A., Et al., The 4G/5G polymorphism of PAI 1 promoter gene as a risk factor for myocardial infarction: A meta analysis, Blood Coagul Fibrinolysis, 8, (1997)

[67]

Henry M., Tregouet D.A., Alessi M.C., Et al., Metabolic determinants are much more important than genetic polymor phisms in determining the PAI-1 activity and antigen plasma concentrations: A family study with part of the Stanislas cohort, Arterioscler Thromb Vasc Biol, 18, pp. 84-91, (1998)

[68]

Van Den Bom J.G., De Knijff P., Haverkate F., Et al., Tissue plasminogen activator and risk of myocardial infarction, Circulation, 95, pp. 2623-2627, (1997)

[69]

Ridker P.M., Baker M.T., Hennekens C.H., Et al., Alu repeat polymorphism in the gene coding for tissue type plasm inogen activator (t-PA) and risk of myocardial infarction among middle-aged men, Arterioscler Thromb Vasc Biol, 17, pp. 1687-1690, (1997)

[70]

Friederich P.W., Levi M., Biemond B.J., Et al., Novel low molecular weight inhibitor of PAI 1 (XR5118) promotes endogenous fibrinolysis and reduces post thrombolysis thrombus growth in rabbits, Circulation., 96, pp. 916-921, (1997)

← 1 2 3 4 5 6 7 →