Elevated Glucose Concentrations Increase Factor VIIIR:Ag Levels in Human Umbilical Vein Endothelial Cells

Mordes, David; Lazarchick, John; Colwell, John A.; Sens, Donald A.

doi:10.2337/diab.32.9.876

Cited by 18 publications

(10 citation statements)

References 9 publications

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“…How, then, may the changes in plasma vWF levels observed in our patients, who had normal urinary albumin excretion, be explained? vWF levels may be influenced by age [23] and, possibly, by glycaemic control [16,17,24], but, as these factors were similar in patients with and without increases in plasma vWF, they are an unlikely explanation for the differences in vWF level changes observed. As diabetic nephropathy is associated with both high vWF concentrations and a high incidence of cardiovascular disease [3-5, 15, 16], and as atherosclerosis in non-diabetic patients is also associated with high vWF levels [25,26], we propose that diabetic patients with normal urinary albumin excretion and high or increasing vWF levels have clinically silent endothelial dysfunction, which may indicate an increased risk of developing nephropathy and cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with Type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion

et al. 1992

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High plasma levels of von Willebrand factor, an indicator of endothelial cell dysfunction, have been reported in both diabetic retinopathy and nephropathy. It is unclear, however, whether von Willebrand factor is related to diabetic retinopathy in the absence of diabetic nephropathy. The relationship between retinal status and plasma von Willebrand factor concentration was investigated in a cohort of 17 patients with Type 1 (insulin-dependent) diabetes mellitus who were followed-up for a median of 42 months. The patients were examined three times. They were selected for having had normal urinary albumin excretion and no evidence of retinopathy (on fundoscopy) at the first and second examination. They were then divided into two groups, according to absence (Group A; n = 9) or presence (Group B; n = 8) of retinopathy on fundoscopy or fluorescein angiography at the third examination. Urinary albumin excretion remained normal in all patients. Plasma von Willebrand factor levels were similar in both groups: (median) 128 vs 123%, 164 vs 132% and 159 vs 130% (first, second and third examination, respectively). Median changes in plasma von Willebrand factor were also similar: +7 vs +9% and +5 vs +1% (first-second and second-third examination). Patients in whom the plasma von Willebrand factor concentration increased had higher systolic blood pressure at the third examination (150 +/- 30 vs 130 +/- 12 mmHg, p = 0.02) when compared to those in whom plasma von Willebrand factor did not increase, but were of similar age and had similar diabetes duration, retinal status, diastolic blood pressure, glycated haemoglobin and serum cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with Type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion

et al. 1992

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“…It is not known whether the clearance of vWF is also affected by diabetic microangiopathy, nor what causes endothelial cells to produce more vWF. A study in vitro had reported increased intracellular content of vWF in cultured endothelium subjected to glucose concentrations mimicking those found in poorly-controlled patients [113].…”

Section: Haemostasismentioning

confidence: 94%

Endothelial cell function in diabetic microangiopathy

et al. 1987

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“…As a glucose-independent control, 3-actin was used. Beside connective tissue proteins, these target molecules can be components of the clotting system like the von Willebrand Factor, which is regulated by glucose (Mordes et al, 1983), or possibly adhesion molecules like ICAM-1 (Simmons et al, 1988). In the latter case, a direct glucose regulation was not observed up to now but there is some evidence that adhesion molecule-triggered monocyte binding to endothelial cells is increased by glucose (Kim et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Glucose-induced fibronectin expression in endothelial cells is mediated by Protein Kinase C

Mueller¹,

Fritsche²,

Haslinger³

et al. 2009

Exp Clin Endocrinol Diabetes

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One of the crucial pathophysiological changes in diabetic angiopathy might be the glucose-induced synthesis of components of the extracellular matrix-like fibronectin. This effect has been described for endothelial and mesangial cells. In order to gain further insight into the mechanisms how glucose-induced fibronectin expression is regulated, confluent monolayers of human umbilical vein endothelial cells (HUVEC) were incubated with varying concentrations of D-glucose (5-30 mM) in a time-dependent manner. Using Westernblotting techniques with a monoclonal antibody, a 3 +/- 0.2-fold increase of the 220 kDa-signal corresponding to human fibronectin was visible after an incubation time of 6 h indicating de-novo synthesis. Using incubation times of 6 or 10 days, glucose-mediated fibronectin overexpression was still visible, reaching a maximum at 15 mM D-glucose. The corresponding maximum values were 2.4 +/- 0.3 (6 d) and 2.3 +/- 0.2 (10 d). There was a concomitant glucose-dependent onset of expression of Protein Kinase C (PKC)-isoforms PKC-delta (2.5 +/- 0.3-fold), PKC-epsilon (2 +/- 0.2-fold) and PKC-zeta (1.8 +/- 0.2-fold), which reached a maximum after 12 h and was still visible during long-term culture. Induction of fibronectin expression was also obtained using the PKC-activating phorbolester Phorbol-12-myristat-13-acetat (PMA) which mimicks glucose-induced PKC activation. Glucose-induced fibronectin expression was decreased by the PKC-inhibitor H-7 (1- [5-isoquinolinylsulfonyl]-2-methylpiperazine). These experiments suggest that: 1. Short-term induction of fibronectin expression mediated by glucose is probably PKC-triggered since concomitant induction of PKC-isoforms PKC-delta, PKC-epsilon and PKC-zeta was observed. 2. Long-term incubation with D-glucose leads to an ongoing concentration-dependent coexpression of fibronection and various PKC-isoforms. If glucose-induced, PKC-mediated de-novo synthesis of components of the connective tissue or the extracellular matrix may be important in the pathomechanism of diabetic angiopathy, has to be proven.

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Elevated Glucose Concentrations Increase Factor VIIIR:Ag Levels in Human Umbilical Vein Endothelial Cells

Cited by 18 publications

References 9 publications

von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with Type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion

von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with Type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion

Endothelial cell function in diabetic microangiopathy

Glucose-induced fibronectin expression in endothelial cells is mediated by Protein Kinase C

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