Fluvastatin and Tissue Factor Pathway Inhibitor in Type Iia and Iib Hyperlipidemia and in Acute Myocardial Infarction

Lorena, Marcelo dos Santos Voltani; Perolini, S.; Casazza, Franco; Milani, Massimo; Cimminiello, Claudio

doi:10.1016/s0049-3848(97)00143-6

Cited by 16 publications

(13 citation statements)

References 26 publications

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“…These results are in agreement with previous studies on AMI patients treated with aspirin reporting normal total TFPI levels at 10 days [8] and 2 weeks after MI [9]. In contrast Falciani et al [10] studied patients who had MI 6-12 months before the study and had not taken antiplatelet drugs before the blood sampling, and found that their plasma TF and TFPI levels were significantly higher than those found in the control subjects.…”

Section: Discussionsupporting

confidence: 92%

“…Rapid changes in the plasma concentrations of von Willebrand factor (vWF) are features of the acute-phase reaction induced by tissue damage, and have been reported during the acute phase of MI [6,7]. It has recently been reported that patients with acute MI (AMI) show elevated plasma levels of tissue factor (TF) and TF pathway inhibitor (TFPI) [8][9][10]. This activity of the hemostatic system leads to a procoagulant state in acute-phase MI patients that is not completely neutralized by the different doses of heparin used [11].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Elevated Thrombotic Activity after Myocardial Infarction: A 2-Year Follow-Up Study

Martínez‐Sales¹,

Vila²,

Regañón³

et al. 1998

Pathophysiol Haemos Thromb

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This study examines the evolution of the thrombotic activity in patients with myocardial infarction (MI) treated with aspirin (200 mg/day) for 2 years after MI. Plasma samples of 10 patients were collected at 7, 30, 60, 90, 120, 150, 180, 360 and 720 days. In all the samples we measured fibrinogen (Fg), high molecular weight Fg (HMW-Fg), fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), β-thromboglobulin (β-TG), von Willebrand factor (vWF), tissue factor (TF) and TF pathway inhibitor (TFPI). The plasma Fg, HMW-Fg, FPA, F1+2, β-TG and vWF levels were significantly elevated in the patients at the beginning of the study as compared to the normal group. The 95% confidence intervals were Fg 277–333 mg/dl, HMW-Fg 200–244 mg/dl, FPA 5.3–16.5 ng/ml, F1+2 1.4–1.8 nmol/l, β-TG 110–118 IU/ml and vWF 139–195%. At thirty days Fg and HMW-Fg returned to normal levels, whereas the increase in FPA and F1+2 levels persisted throughout the study. At 120 and 150 days, respectively, β-TG and vWF returned to normal levels. The increase in thrombin generation and activity pointed to a persistent hypercoagulable state 2 years after MI. Plasma levels of TF and TFPI showed no statistically significant variations with respect to the normal values over the 2-year period studied. In conclusion, these results suggest a persistent generation and activity of thrombin and cellular activation in these patients after MI.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Elevated Thrombotic Activity after Myocardial Infarction: A 2-Year Follow-Up Study

Martínez‐Sales¹,

Vila²,

Regañón³

et al. 1998

Pathophysiol Haemos Thromb

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“…Treatment with HMG‐CoA reductase inhibitor was shown to induce a significant reduction of total TFPI antigen levels 83, 86. This reduction in TFPI levels may result from normalization of an up‐regulated clotting system rather than an unfavourable reduction of a natural anticoagulant 86.…”

Section: Variables That Could Potentially Influence Tfpi Activitymentioning

confidence: 99%

Tissue factor pathway inhibitor: structure, biology and involvement in disease

Lwaleed

Bass

2005

The Journal of Pathology

177

120

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Tissue factor (TF)-initiated coagulation plays a significant role in the pathophysiology of many diseases, including cancer and inflammation. Tissue factor pathway inhibitor (TFPI) is a plasma Kunitz-type serine protease inhibitor, which modulates initiations of coagulation induced by TF. In a factor (F) Xa-dependent feedback system, TFPI binds directly and inhibits the TF-FVII/FVIIa complex. Normally, TFPI exists in plasma both as a full-length molecule and as variably carboxy-terminal truncated forms. TFPI also circulates in complex with plasma lipoproteins. The levels and the dual inhibitor effect of TFPI on FXa and TF-FVII/FVIIa complex offers insight into the mechanisms of various pathological conditions triggered by TF. The use of selective pharmacological inhibitors has become an indispensable tool in experimental haemostasis and thrombosis research. In vivo administration of recombinant TFPI (rTFPI) in an experimental animal model prevents thrombosis (and re-thrombosis after thrombolysis), reduces mortality from E. coli-induced-septic shock, prevents fibrin deposition on subendothelial human matrix and protects against disseminated intravascular coagulation (DIC). Thus, TFPI may play an important role in modulating TF-induced thrombogenesis and it may also provide a unique therapeutic approach for prophylaxis and/or treatment of various diseases. In this review, we consider structural and biochemical aspects of the TFPI molecule and detail its inhibitory mechanisms and therapeutic implications in various disease conditions.

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“…However, conflicting results have been reported. 5,8 Lovastatin, 69 fluvastatin, 70 simvastatin, 36 and atorvastatin 36 have been found to decrease TFPI activity, caused by reduction in the LDL-TFPI complexes, and total TFPI levels without any change in free TFPI in hyperlipidemic individuals. The reported lower TFPI antigen levels as a result of the HMG-CoA reductase inhibitors are likely to reflect normalization of the disturbed functions of the endothelium, but not suppression of the anticoagulant potency of the endothelial pool of free TFPI, mobilized by heparin, as shown by Hansen et al 69 The available data indicate a lack of significant changes in TFPI levels and/or activity during statin therapy.…”

Section: Tissue Factor Pathway Inhibitormentioning

confidence: 99%

Statins and Blood Coagulation

Undas

Brummel‐Ziedins²,

Mann³

2005

ATVB

241

192

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Abstract-The 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) have been shown to exhibit several vascular protective effects, including antithrombotic properties, that are not related to changes in lipid profile. There is growing evidence that treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation. Accordingly, statin use has been associated with impairment of several coagulant reactions catalyzed by this enzyme. Moreover, evidence indicates that statins, via increased thrombomodulin expression on endothelial cells, may enhance the activity of the protein C anticoagulant pathway. Most of the antithrombotic effects of statins are attributed to the inhibition of isoprenylation of signaling proteins. These novel properties of statins, suggesting that these drugs might act as mild anticoagulants, may explain, at least in part, the therapeutic benefits observed in a wide spectrum of patients with varying cholesterol levels, including subjects with acute coronary events. Key Words: statins Ⅲ blood coagulation Ⅲ thrombin Ⅲ protein C T he 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase inhibitors, the so-called statins, have been proven to be highly effective in the management of hyperlipidemia and the prevention of atherosclerotic vascular disease, especially coronary artery disease (CAD). 1,2 The therapeutic benefits from statin therapy, however, are only poorly correlated with cholesterol lowering, suggesting other mechanisms are at play. Mevalonate, the product of HMGCoA reductase, is the precursor of not only cholesterol but also isoprenoid compounds that permit the attachment of signaling proteins to the cell membrane. 3,4 Abundant experimental and clinical evidence in this rapidly expanding field has resulted in the widely accepted concept of cholesterol-independent pleiotropic effects produced by statins that include alteration of endothelial dysfunction, leading to increased nitric oxide (NO) bioavailability, atherosclerotic plaque stabilization, regulation of angiogenesis, reduction of the inflammatory response, and antithrombotic properties. [5][6][7] Apart from profibrinolytic and antiplatelet effects, reported in several studies, 5,7-9 increasing evidence indicates that the HMG-CoA reductase inhibitors also modulate the blood coagulation cascade at multiple levels, leading to reduced thrombogenicity.The activation of the extrinsic coagulation pathway initiated by an exposure or expression of tissue factor (TF) plays a key role in hemostasis (Figure). The localized process involves multiple components, including blood coagulation factors, platelets, blood cells, the endothelium, and sublayers of a damaged vessel. Platelets provide the catalytic surface for the formation of the procoagulant complexes; the intrinsic factor Xase (FIXa-FVIIIa) and prothrombinase (prothrombin, FXa-FVa). These complexes accelerate thrombin ge...

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Fluvastatin and Tissue Factor Pathway Inhibitor in Type Iia and Iib Hyperlipidemia and in Acute Myocardial Infarction

Cited by 16 publications

References 26 publications

Elevated Thrombotic Activity after Myocardial Infarction: A 2-Year Follow-Up Study

Elevated Thrombotic Activity after Myocardial Infarction: A 2-Year Follow-Up Study

Tissue factor pathway inhibitor: structure, biology and involvement in disease

Statins and Blood Coagulation

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