Increased Tissue Factor Pathway Inhibitor Activity in IDDM Patients With Nephropathy

Yokoyama, Hiroyuki; Myrup, B.; Rossing, Peter; Østergaard, Per

doi:10.2337/diacare.19.5.441

Cited by 31 publications

(30 citation statements)

References 30 publications

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“…Yokoyama et al [22] observed that TFPI concentrations were increased in insulin-dependent diabetes mellitus patients compared with control individuals. They also observed that increased plasma TFPI activity in these patients may be associated with and regulated by lowdensity lipoprotein in plasma and metabolic control individuals.…”

Section: Discussionmentioning

confidence: 98%

Study of factor VII, tissue factor pathway inhibitor and monocyte tissue factor in noninsulin-dependent diabetes mellitus

Elghoroury

El-Din

Abdelkader

et al. 2008

Blood Coagulation &Amp; Fibrinolysis

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Changes in plasma tissue factor (TF)-activated factor VII (FVIIa) and plasma tissue factor pathway inhibitor (TFPI) in type II diabetes mellitus are assessed, vascular complicated and noncomplicated patients compared, and whether these novel hemostatic activity markers predict vascular complications in diabetic patients, improving risk assessment, is determined. Fifty type II diabetic patients and 20 healthy controls (age, sex and body mass matched) underwent medical history and examination, fasting plasma glucose level, glycosylated hemoglobin (HbA1c), lipid profile, hemostatic parameters, plasma TF activity, and TFPI and TF expression on blood monocytes. Mean TF, TF activity, TFPI, and FVIIa significantly increased among hyperlipidemic compared with normolipidemic diabetic patients, and normolipidemic diabetic patients compared with controls. Mean percentage TF-positive monocytes with and without lipopolysaccharide, plasma TF activity, TFPI and FVIIa were significantly higher among complicated than noncomplicated diabetic patients. Mean percentage TF-positive monocytes without and with lipopolysaccharide, plasma TF activity, plasma TFPI and FVIIa were higher among diabetic patients with macrovascular compared with microvascular complications. High significant correlation occurred between HbA1c, triglycerides and percentage TF-positive monocytes with and without lipopolysaccharide stimulation, plasma TF activity and both FVIIa and TFPI. High activity levels of plasma TF and FVIIa with increased circulating TF-positive monocytes occurred in type II diabetic patients, especially with vascular complications. Results reflect high procoagulant activity possibly involved in diabetic vascular complications. Elevated TFPI levels were observed, but were not sufficient to balance high procoagulant activity. Correlation of procoagulant activity markers with HbA1c reinforces the importance of optimal glycemic control in type II diabetes.

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Section: Discussionmentioning

confidence: 98%

Study of factor VII, tissue factor pathway inhibitor and monocyte tissue factor in noninsulin-dependent diabetes mellitus

Elghoroury

El-Din

Abdelkader

et al. 2008

Blood Coagulation &Amp; Fibrinolysis

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“…Furthermore, several reports claim that diabetes mellitus is associated with changes in the hemostatic system [6,7,8]. Such changes are more pronounced in patients with diabetic nephropathy than in diabetic patients without renal complications [9,10,11,12,13,14,] again suggesting that coagulation activation is associated with diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 94%

“…The presence of fibrin, the final product of the coagulation cascade, in glomeruli suggests a role for the blood coagulation system in the pathogenesis of diabetic nephropathy [4, 5]. To some extent this process may be influenced by the hypercoagulable state of blood from diabetic patients, which is even more pronounced in patients with nephropathy [9,10,11,12,13,14]. In analogy with other renal diseases, we speculated that local activation of the blood coagulation system, particularly the production of TF and specific proteases such as thrombin that may induce biological effects unrelated to fibrin formation, would contribute to organ damage.…”

Section: Discussionmentioning

confidence: 99%

Renal Tissue Factor Expression Is Increased in Streptozotocin-Induced Diabetic Mice

Sommeijer¹,

Florquin²,

Hoedemaker³

et al. 2005

Nephron Exp Nephrol

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Background: Tissue factor (TF) is the key initiator of the coagulation cascade. Recent evidence suggests that TF plays a role in renal fibrin formation and renal failure in experimental kidney disease. We hypothesized that hyperglycemia is an important stimulus of TF expression in the kidney. Methods: Mice were injected with streptozotocin (STZ) (200 mg/kg) or with control buffer. Three or 10 weeks after injection, fibrin, thrombin and TF staining and TF activity were evaluated in the kidney. The effect of hyperglycemia on TF expression and secretion by tubular epithelial cells was measured in vitro. Results: Kidneys of STZ-treated mice showed a marked increase in thrombin staining (3.0 ± 0.5 vs. 1.2 ± 0.11) (p = 0.002) and an increase in TF clotting activity 10 weeks after STZ injection (33.9 ± 1.3 vs. 25.4 ± 1.0 s) (p < 0.0001). Increased glomerular fibrin deposition was present in 3 out of 6 diabetic mice. Tubular cells incubated with D-glucose (25 mmol/l) for 48 h displayed increased cellular TF (p = 0.05). However, soluble TF levels and TF activity in supernatant of cells incubated with D- or L-glucose were not different. Conclusions: These data suggest that hyperglycemia is a causal factor in procoagulant activity associated with diabetic nephropathy.

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“…Growth factors such as transforming growth factor-b (TGF-b), which could be extraordinarily enhanced by hyperglycemia, elevated levels of systemic blood pressure and intraglomerular pressure, and glycated proteins in patients with diabetes, would affect synthesis of extracellular matrix proteins within glomerular basement membrane and vascular wall [41]. Moreover, a number of proteins (i.e., lipoprotein lipase, tissue factor pathway inhibitor, platelet factor 4, and antithrombin III) are anchored to the vascular wall via interaction with the chains of HS-PG [11,42,43]. Such alterations may potentiate albuminuria and several of the processes involved in atherogenesis [41].…”

Section: Disease Processmentioning

confidence: 99%

Subclinical atherosclerosis is increased in type 2 diabetic patients with microalbuminuria evaluated by intima-media thickness and pulse wave velocity

Yokoyama

Aoki

Imahori

et al. 2004

Kidney International

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135

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Increased Tissue Factor Pathway Inhibitor Activity in IDDM Patients With Nephropathy

Cited by 31 publications

References 30 publications

Study of factor VII, tissue factor pathway inhibitor and monocyte tissue factor in noninsulin-dependent diabetes mellitus

Study of factor VII, tissue factor pathway inhibitor and monocyte tissue factor in noninsulin-dependent diabetes mellitus

Renal Tissue Factor Expression Is Increased in Streptozotocin-Induced Diabetic Mice

Subclinical atherosclerosis is increased in type 2 diabetic patients with microalbuminuria evaluated by intima-media thickness and pulse wave velocity

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