Non-enzymatic glycation reduces heparin cofactor II anti-thrombin activity

Ceriello, Antonio; Marchi, E.; Barbanti, M.; Milani, Mario; Giugliano, Dario; Quatraro, A; Pj, Lefèbvre

doi:10.1007/bf00404797

Cited by 32 publications

(19 citation statements)

References 18 publications

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“…Other important features of AGE-induced vasculopathy include effects on coagulation and fibrinolysis (Table 1); specifically, reduced platelet survival and increased aggregation [105,106], alterations in coagulation factors such as anti-thrombin-III, tissue factor and thrombomodulin [12], and effects on fibrin stabilisation [107]. The end result is the promotion of a procoagulant state.…”

Section: Consequences Of Age Formation In Diabetesmentioning

confidence: 99%

Advanced glycation end-products: a review

et al. 2001

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Diabetes is a common condition with multiple complications. There has been much work done to elaborate on the aetiology, prevention and treatment of diabetes related complications. The DCCT [1] and UKPDS [2] studies have emphasised the role of tight glucose control as being important in reducing diabetic microvascular disease in Type I (insulin-dependent) diabetes mellitus (DCCT) and Type II (non-insulin-dependent) diabetes mellitus (UKPDS). The relation between tight glucose control and macrovascular complications is, however, not clear [3]. Recently the importance of blood pressure control in reducing diabetic microvascular complications has been shown [4]. Apart from these factors, damage induced by hyperglycaemia involves a complex interaction between many influences including genetic predisposition, smoking, BMI, dyslipidaemia and alterations in coagulation factors [3]. The presence of advanced glycation end-products (AGE) is closely related to Diabetologia (2001) AbstractAdvanced glycation end-products are a complex and heterogeneous group of compounds that have been implicated in diabetes related complications. At present it is not known if they are the cause or the consequence of the complications observed. We discuss the chemistry of advanced glycated end-product formation and their patho-biochemistry particularly in relation to the diabetic microvascular complications of retinopathy, neuropathy and nephropathy as well as their role in the accelerated vasculopathy observed in diabetes. The concept of carbonyl stress as a cause for advanced glycated end-product toxicity is mentioned. We discuss alterations in the concentrations of advanced glycated end-products in the body, particularly in relation to changes occuring with age, diabetes and its complications such as nephropathy. Problems relating to current methods of advanced glycated end-product detection and measurement are highlighted including the lack of a universally established method of detection or unit of measurement. Agents used for the treatment of advanced glycated end-product accumulation are reviewed, with an emphasis on the results of the recent phase III trials using aminoguanidine and diabetes related complications. [Diabetologia (2001) 44: 129±146]Keywords Advanced glycated end-products, diabetes mellitus, microvascular disease, carbonyl stress, aminoguanidine.Corresponding author: Dr R. Singh MRCP (UK), FRACP, University Dept of Medicine, Royal Perth Hospital, PO Box X2213, Perth 6847, Western Australia Abbreviations: ESRD, End-stage renal disease; 3-DG, 3-deoxyglucosone; MGO, methylglyoxal; DOLD, deoxyglucosone-lysine dimer; MOLD, methyl glyoxal-lysine dimer; CML, N e -[carboxymethyl]-lysine; FFI, furoyl-furanyl imidazole; PTB, phenacyl thiozolium bromide; RAGE, receptor for AGE; NF-kB, nuclear factor-kB; VCAM-1, vascular cell adhesion molecule-1; ICAM-1, intracellular adhesion molecule-1; PECAM-1, platelet endothelial cell adhesion molecule-1; ELAM-1, endothelial leucocyte adhesion molecule-1; MSR, macrophage scavenger recepto...

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Section: Consequences Of Age Formation In Diabetesmentioning

confidence: 99%

Advanced glycation end-products: a review

et al. 2001

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“…Indeed, non-enzymatic glycation of fibrinogen shows a significant resistance in susceptibility to plasmin degradation (Murakami et al, 1990), while AGE-modification of annexin II impairs the appropriate formation of the t-PA/annexin II complex, thus disturbing the fibrinolytic system as well (Gugliucci et al, 2002). Glycated heparin cofactor II is also shown to lose its antithrombin activity in diabetes (Ceriello et al, 1990).…”

Section: Ages and Anti-fibrinolysismentioning

confidence: 98%

Role of Advanced Glycation End Products (AGEs) in Thrombogenic Abnormalities in Diabetes

Takenaka

Yamagishi²,

Matsui³

et al. 2006

CNR

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Accelerated atherosclerosis and microvascular complications are perhaps the leading cause of coronary heart disease, blindness and renal failure, which could account for disabilities and high mortality rates in patients with diabetes. Several thrombogenic abnormalities have been shown to play a central role in the pathogenesis of these devastating complications. However, the molecular mechanism for thrombogenic diathesis in diabetes is not fully elucidated. A recent clinical study, the Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) Research, has revealed that the reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persist for at least several years, despite increasing hyperglycemia. Further, intensive therapy during the DCCT resulted in decreased progression of carotid intima-media thickness six years after the end of the trial as well. These clinical studies strongly suggest that so-called 'hyperglycemic memory' causes chronic abnormalities in diabetic vessels that are not easily reversed, even by subsequent, relatively good control of blood glucose. Among various biochemical pathways activated under diabetes, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the theory 'hyperglycemic memory'. In this review, we discuss the role of AGEs in thrombogenic abnormalities in diabetes.

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“…HCII and antithrombin III inactivate thrombin by similar mecha nisms [1], Clinical studies on antithrombin III in diabetes have provided evidence for a reduction in the biological activity of anti thrombin III, despite normal plasma concen tration [9][10][11][12][13], and this phenomenon seems to be due to a nonenzymatic glycation pro cess [5][6][7], The nonenzymatic glycation of HCII has been recently shown [18]. Interest ingly, this phenomenon, occurring at glucose concentrations that may be encountered in the plasma of diabetic patients, is capable to reduce HCII antithrombin activity [18], Thus a role of in vivo nonenzymatic glyca tion in determining this phenomenon may be hypothesized.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies of the fluid phase of coagula tion suggest that diabetes is associated with a hypercoagulable state [3,4], It is well known that the nonenzymatic glycation of another protease inhibitor, antithrombin III, pro duces a significant decrease in thrombininhibiting activity in vitro [5][6][7] and that in insulin-dependent diabetics the degree of re duction was shown to be related directly to the level of Hb A1 [8], glycated proteins [9] and fasting blood glucose [ 10], Furthermore, heparin [11] or low-molecular-weight hepa rin [12] administration and the achievement of improved metabolic control [13,14] were able to restore antithrombin III activity in diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Evidence for a Reduced Heparin Cofactor II Biological Activity in Diabetes

Ceriello¹,

Quatraro²,

et al. 1990

Pathophysiol Haemos Thromb

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A reduction of heparin cofactor II (HCII) biological activity, despite its normal plasma concentration, is reported in insulin-dependent diabetic patients. A good linear correlation between HCII activity and concentration is present in normal controls but not in diabetics. In these subjects HCII activity correlates inversely with fasting blood glucose and glycated proteins but not with Hb A₁. These data demonstrate the presence of a depressed HCII activity in the presence of its normal plasma concentration in insulin-dependent diabetics and suggest a role for short-term metabolic control in conditioning this phenomenon.

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Non-enzymatic glycation reduces heparin cofactor II anti-thrombin activity

Cited by 32 publications

References 18 publications

Advanced glycation end-products: a review

Advanced glycation end-products: a review

Role of Advanced Glycation End Products (AGEs) in Thrombogenic Abnormalities in Diabetes

Evidence for a Reduced Heparin Cofactor II Biological Activity in Diabetes

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