Plasminogen Activator Inhibitor‐1: Physiologic Role, Regulation, and the Influence of Common Pharmacologic Agents

Tsikouris, James P.; Suárez, José; Meyerrose, Gary

doi:10.1177/009127002762491271

Cited by 44 publications

(27 citation statements)

References 133 publications

(123 reference statements)

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“…, the major inhibitor of endogenous thrombolysis, thereby promoting thrombosis (7). Hyperhomocysteinemia, a consequence of disturbed methionine metabolism, appears also to be an independent risk factor for atherothrombotic events, even in diabetic subjects (8).…”

Section: It Is Well-known That Diabetes Changes the Thrombohaemorrhagmentioning

confidence: 99%

Effects of Nateglinide and Glibenclamide on Prothrombotic Factors in Naieve Type 2 Diabetic Patients Treated with Metformin: A 1-Year, Double-Blind, Randomized Clinical Trial

et al. 2007

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Objective (FPI), postprandial plasma insulin (PPI), homeostasis model assessment index (HOMA index), lipid profile with lipoprotein (a) [Lp(a)], fibrinogen (Fg), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), homocysteine (Hcy), systolic blood pressure (SBP), diastolic blood pressure (DBP).Results After 9 months of treatment, both tested drug combinations were similarly associated with a significant reduction in FPG (nateglinide, glibenclamide, both p<0.05) p<0.01), p<0.01, p<0.05), p< 0.05); the glibenclamide group, showed a significant reduction in HbA1c p<0.05), p< 0.05), p<0.05), and HOMA index (-23.9%, p<0.05) but to a minor extent. Moreover, the HbA1c difference value from baseline observed in the nateglinide-treated group was significantly higher than that observed in the glibenclamide group. Therefore the nateglinide-treated patients showed a significant reduction in some prothrombotic parameters all p<0.05), whereas the glibenclamide-treated patients did not. Conclusion Nateglinide appears to improve glycemic control as well as the levels of some prothrombotic parameters compared to glibenclamide when administered in combination with metformin.

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Section: It Is Well-known That Diabetes Changes the Thrombohaemorrhagmentioning

confidence: 99%

Effects of Nateglinide and Glibenclamide on Prothrombotic Factors in Naieve Type 2 Diabetic Patients Treated with Metformin: A 1-Year, Double-Blind, Randomized Clinical Trial

et al. 2007

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“…A major function of PAI-1 is the inactivation of tissue-type plasminogen (tPA) and urokinase-type plasminogen (uPA) activators, through covalent binding of PAI-1 to tPA or uPA, resulting in decreased plasmin activity and fibrinolytic potential (1)(2)(3). Through its involvement in the fibrinolytic pathway, PAI-1 has been shown to play a significant role in thrombotic-induced diseases, including venous thrombosis (4,5) and the acute coronary syndrome, wherein serum levels of PAI-1 increase upon coronary occlusion and predict future coronary events in human subjects (6 -8).…”

Section: P Lasminogen Activator Inhibitor-1 (Pai-1)mentioning

confidence: 99%

Regulation of Lipopolysaccharide-Induced Lung Inflammation by Plasminogen Activator Inhibitor-1 through a JNK-Mediated Pathway

Arndt

Young

Worthen

2005

The Journal of Immunology

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The neutrophil is of undoubted importance in lung inflammation after exposure to LPS. We have shown recently that systemic inhibition of JNK decreased neutrophil recruitment to the lung after exposure to LPS, although the mechanisms underlying this inhibition are incompletely understood. As plasminogen activator inhibitor-1 (PAI-1) accentuates cell migration, with JNK activation recently shown to up-regulate PAI-1 expression, this suggested that systemic JNK inhibition may down-regulate LPS-induced pulmonary neutrophil recruitment through a decrease in PAI-1 expression. We show in this study that exposure of mice to aerosolized LPS increased PAI-1 expression in the lung and alveolar compartment, which was decreased by pretreatment with the JNK inhibitor SP600125. Exogenous, intratracheally administered PAI-1 prevented the inhibition of pulmonary neutrophil recruitment in the setting of systemic JNK inhibition, thereby suggesting a role for PAI-1 in the JNK-mediated pathway regulating LPS-induced neutrophil recruitment. In addition, PAI-1−/− mice had a decrease in neutrophil recruitment to the alveolar compartment after exposure to LPS, compared with wild-type controls, further suggesting a role for PAI-1 in LPS-induced lung inflammation. An increase in the intravascular level of KC is a likely mechanism for the inhibition of pulmonary neutrophil recruitment after LPS exposure in the setting of decreased PAI-1 expression, as systemic KC levels after exposure to LPS were increased in PAI-1-deficient mice and in mice pretreated with SP600125, with augmentation of intravascular KC levels inhibiting neutrophil recruitment to the lung after exposure to LPS.

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“…An example is pravastatin. 152 Recently, much consideration has been given to relationships between inflammatory processes and accelerated atherosclerosis, particularly in association with diabetes and insulin resistance. Increased PAI-1 expression is associated with inflammation, in part, because of stimulation of PAI-1 expression by cytokines such as interleukins -1 and -6, 153 tumor necrosis factor, and oxygen-centered free radicals 154 and in part because markers of inflammation such as C-reactive protein can themselves increase PAI-1 expression.…”

Section: Factors In Addition To Insulin Resistance That Can Affect Pamentioning

confidence: 99%

Intramural Plasminogen Activator Inhibitor Type-1 and Coronary Atherosclerosis

Sobel

Taatjes

Schneider

2003

ATVB

108

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Abstract-Altered expression of plasminogen activator inhibitor type-1 in vessel walls, reviewed here, might affect coronary atherogenesis. Upregulation might exacerbate vasculopathy by potentiating thrombosis and by inhibiting vascular smooth muscle cell migration, resulting in attenuation of thickness of elaborated fibrous caps implicated in the vulnerability of atheroma to rupture. (Arterioscler Thromb Vasc

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Plasminogen Activator Inhibitor‐1: Physiologic Role, Regulation, and the Influence of Common Pharmacologic Agents

Cited by 44 publications

References 133 publications

Effects of Nateglinide and Glibenclamide on Prothrombotic Factors in Naieve Type 2 Diabetic Patients Treated with Metformin: A 1-Year, Double-Blind, Randomized Clinical Trial

Effects of Nateglinide and Glibenclamide on Prothrombotic Factors in Naieve Type 2 Diabetic Patients Treated with Metformin: A 1-Year, Double-Blind, Randomized Clinical Trial

Regulation of Lipopolysaccharide-Induced Lung Inflammation by Plasminogen Activator Inhibitor-1 through a JNK-Mediated Pathway

Intramural Plasminogen Activator Inhibitor Type-1 and Coronary Atherosclerosis

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