Fluvastin therapy affects TAFI concentration in kidney transplant recipients

Małyszko, Jolanta; Małyszko, J.; Myśliwiec, Michał

doi:10.1111/j.1432-2277.2003.tb00223.x

Cited by 13 publications

(9 citation statements)

References 25 publications

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“…The mechanism underlying association between elevated plasma TAFI and LDL cholesterol in type 2 diabetic patients remains to be determined. Malyszko et al (18) reported that in hyperlipidemic patients undergoing renal transplantation, treatment with a statin brought about significant decreases in both plasma TAFI and LDL cholesterol, supporting present findings of a positive correlation between TAFI and LDL cholesterol.…”

Section: Pai-1 and Tafi In Diabetes With Mssupporting

confidence: 78%

Metabolic Syndrome Accompanied by Hypercholesterolemia Is Strongly Associated With Proinflammatory State and Impairment of Fibrinolysis in Patients With Type 2 Diabetes

et al. 2005

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OBJECTIVE -To determine whether plasma concentrations of thrombin-activatable fibrinolysis inhibitor (TAFI) in patients with type 2 diabetes were associated with components of metabolic syndrome (MS), including high-sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor (PAI)-1, and LDL cholesterol.RESEARCH DESIGN AND METHODS -We studied 136 consecutive patients with type 2 diabetes. Diagnosis of MS was diagnosed by current criteria. Hypercholesterolemia (HC) was defined as serum LDL cholesterol Ͼ140 mg/dl (3.6 mmol/l) or treatment with a statin. For comparisons, diabetic patients were divided into four groups: those with no MS and no HC (n ϭ 38), with MS but not HC (n ϭ 39), with no MS but with HC (n ϭ 26), and with both MS and HC (n ϭ 33).RESULTS -Considering all patients with type 2 diabetes, plasma PAI-1 was strongly associated with MS components such as BMI, triglyceride, alanine aminotransferase, a homeostasis model assessment of insulin resistance, and hs-CRP. Plasma TAFI only correlated positively and independently with LDL cholesterol. Plasma concentrations of plasmin-␣2-antiplasmin complex (PAP), a measure of fibrinolytic activity in blood, showed a significant negative correlation with plasma PAI-1 but not TAFI. Diabetic patients with both MS and HC had the highest serum hs-CRP concentrations and the lowest plasma PAP concentrations.CONCLUSIONS -LDL cholesterol is a main determinant of plasma TAFI in patients with type 2 diabetes. Coexistence of MS and HC synergistically accelerates inflammation and impairment of fibrinolysis via elevated concentrations of both TAFI and PAI-1, which inhibit fibrinolysis. Diabetes Care 28:2211-2216, 2005M etabolic syndrome (MS), also known as insulin resistance syndrome, is defined by the clustering of several cardiovascular risk factors in an individual patient, including impaired glucose tolerance (diabetes), hypertension, dyslipidemia, and visceral obesity (1,2). Several studies have demonstrated that this syndrome strongly predicts cardiovascular disease (CVD), especially coronary heart disease (3,4), independently of LDL cholesterol. Recently, a close association of MS with hemostatic abnormalities has been reported. Among hemostatic abnormalities, an increase in plasma plasminogen activator inhibitor (PAI)-1, a strong inhibitor of fibrinolysis, is considered a core feature of MS (5). High plasma PAI-1 concentrations may be associated with thrombus formation, causing cardiovascular events (6).A new inhibitor of fibrinolysis has been recently identified in plasma. As this protein is activated by thrombin and then downregulates fibrinolysis, it has been named thrombin-activatable fibrinolysis inhibitor (TAFI) (7). TAFI proved to be identical with plasma procarboxypeptidase B, U, or R (8). TAFI removes COOHterminal lysine or arginine residues from partially degraded fibrin, decreasing plasminogen binding to the fibrin surface (9). Since TAFI is associated with coagulation/ fibrinolysis and inflammation, plasma TAFI may participate in arterial thromb...

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Section: Pai-1 and Tafi In Diabetes With Mssupporting

confidence: 78%

Metabolic Syndrome Accompanied by Hypercholesterolemia Is Strongly Associated With Proinflammatory State and Impairment of Fibrinolysis in Patients With Type 2 Diabetes

et al. 2005

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“…Depletion of thyroid hormones leads to a reduced number of LDL receptors in the liver and to decreased biliary excretion of cholesterol resulting in elevated serum LDL. The relationship between LDL cholesterol and TAFI antigen levels have been reported in several studies [30][31][32]. Aso et al [32] found that serum LDL cholesterol is an independent predictor of plasma TAFI levels in type 2 diabetes.…”

Section: Discussionmentioning

confidence: 88%

Elevated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Overt and Subclinical Hypothyroid Patients Were Reduced by Levothyroxine Replacement

et al. 2007

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Abstract. The influence of hypothyroidism on haemostasis is an active research area. Not only bleeding tendency but also hypercoagulable states have been reported in hypothyroid patients. Decreased and increased fibrinolytic activity in hypothyroid patients has been shown in several studies. Thrombin activatable fibrinolysis inhibitor (TAFI) is an inhibitor of fibrinolysis, which has been recently isolated from human plasma. The aim of our study was to determine plasma TAFI antigen levels in overt and subclinical hypothyroidism, and to investigate the effect of levothyroxine treatment on TAFI levels. The study was performed in age-and sex-matched 30 overt hypothyroid, 30 subclinical hypothyroid patients, and 30 healthy controls. Blood samples were obtained from patients with overt and subclinical hypothyroidism before levothyroxine replacement, and one month after achieving a euthyroid state with levothyroxine. TAFI antigen levels were measured using Enzyme-Linked ImmunoSorbent Assay kits (Affinity Biologicals; Ontario, Canada). In baseline evaluation both the overt and subclinical hypothyroid groups had higher TAFI antigen levels than control group (p<0.05). High levels of TAFI antigen were correlated with the degree of thyroid failure. After achieving euthyroid state with levothyroxine replacement, TAFI antigen levels decreased significantly in patients with overt and subclinical hypothyroidism (p<0.05). Our data suggest that there are elevated plasma levels of TAFI antigen both in overt and subclinical hypothyroidism, which may be associated with hypofibrinolysis and elevated risk of thrombosis. Normalization of thyroid state by levothyroxine replacement seems to be effective in lowering of TAFI antigen levels in hypothyroidism.

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“…It has been demonstrated that TAFI is expressed in adipocytes, which might explain the association of plasma TAFI concentrations with metabolic disturbances [62,71]. Positive associations between TAFI and low density lipoprotein cholesterol have been noted [48]; accordingly, simvastatin and fluvastatin therapies have been shown to decrease plasma TAFI concentrations [72][73][74]. Finally, decreases in plasma TAFI concentrations have been noted in the case of different diseases of the liver, in keeping with the hepatic site of expression of plasma-derived TAFI [75][76][77], and may or may not correlate with increased plasma fibrinolysis [76,77].…”

Section: Non-genetic Influences On Plasma Tafi Concentrationsmentioning

confidence: 98%

Curiouser and curiouser: Recent advances in measurement of thrombin-activatable fibrinolysis inhibitor (TAFI) and in understanding its molecular genetics, gene regulation, and biological roles

Boffa

Koschinsky

2007

Clinical Biochemistry

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Fluvastin therapy affects TAFI concentration in kidney transplant recipients

Cited by 13 publications

References 25 publications

Metabolic Syndrome Accompanied by Hypercholesterolemia Is Strongly Associated With Proinflammatory State and Impairment of Fibrinolysis in Patients With Type 2 Diabetes

Metabolic Syndrome Accompanied by Hypercholesterolemia Is Strongly Associated With Proinflammatory State and Impairment of Fibrinolysis in Patients With Type 2 Diabetes

Elevated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Overt and Subclinical Hypothyroid Patients Were Reduced by Levothyroxine Replacement

Curiouser and curiouser: Recent advances in measurement of thrombin-activatable fibrinolysis inhibitor (TAFI) and in understanding its molecular genetics, gene regulation, and biological roles

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