2013
DOI: 10.1371/journal.pone.0055396
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The Oxidative Modification of Von Willebrand Factor Is Associated with Thrombotic Angiopathies in Diabetes Mellitus

Abstract: The thrombogenic activity of Von Willebrand factor (VWF) is proportional to its molecular size and inversely related to its proteolysis by ADAMTS-13. Oxidation of VWF severely impairs its proteolysis by the metalloprotease. This study was aimed at assessing in patients with type 1 and type 2 diabetes whether protein carbonyls, marker of oxidative stress, are associated with both the level and oxidation status of VWF as well as with micro- and macroangiopathic complications. Eighty-three diabetic patients (41 t… Show more

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Cited by 35 publications
(23 citation statements)
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References 47 publications
(58 reference statements)
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“…Following a fresh frozen plasma infusion (total dose 800 mL), the monitoring of ADAMTS-13 activity showed a level of 24%. The symptoms of the boy improved progressively, the haematuria and the schistocytes progressively disappeared and at present the patient is periodically receiving fresh frozen plasma infusions, when blood cells controls showed a significant decrease of platelet count (usually every LGT-agarose) as previously reported (24). Von Willebrand factor antigen and activity was measured by immunoassays, using commercially available assays and an automatic chemiluminometer …”
Section: Case Reportmentioning
confidence: 73%
“…Following a fresh frozen plasma infusion (total dose 800 mL), the monitoring of ADAMTS-13 activity showed a level of 24%. The symptoms of the boy improved progressively, the haematuria and the schistocytes progressively disappeared and at present the patient is periodically receiving fresh frozen plasma infusions, when blood cells controls showed a significant decrease of platelet count (usually every LGT-agarose) as previously reported (24). Von Willebrand factor antigen and activity was measured by immunoassays, using commercially available assays and an automatic chemiluminometer …”
Section: Case Reportmentioning
confidence: 73%
“…3 However, to date there is no experimental evidence to suggest a causal role for ULVWF multimers in the exacerbation of diabetic nephropathy. One can speculate that ULVWF multimers might be simply an associated marker of disease status, possibly secondary to endothelial cell dysfunction and/or oxidative stress.…”
Section: Discussionmentioning
confidence: 99%
“…2 Oxidative stress was shown to be associated with accumulation of ultra-large von willebrand factor (ULVWF) multimers and thrombotic angiopathy in patients with diabetic nephropathy. 3 Notably, ULVWF multimers, which are stored in platelet α-granules and endothelial Weibel-Palade bodies, are extremely large (up to 20,000 kDa) and are considered to be prothrombogenic. ULVWF multimers are not present in the plasma of healthy individuals because, upon release from platelets or endothelial cells, they are rapidly cleaved by the plasma protease ADAMTS13 (A Disintegrin And Metalloprotease with Thrombospondin type I repeats-13) into less active, smaller VWF multimers.…”
Section: Introductionmentioning
confidence: 99%
“…Some of the apparent downstream consequences of this excess ROS and RNS production in the face of high glucose were previously noted and include: uncoupling of eNOS and consumption of NO to produce peroxinitrite; nitration and inhibition of PGIS with diversion of PGH 2 to inflammatory TP signaling and adhesion molecule expression (2123); inhibition of protective ERK5 (1977); increased 12-S-HETE production by 12/ 15-LO together with proinflammatory fibronectin presentation (1395,1396); increased expression of BMP4 and BMP2 and their receptors (185); premature endothelial senescence with inhibition of SIRT1 (210); oxidation of vWF preventing its proteolysis and causing predisposition to thrombosis (1328); and induction of the inflammatory cytokine OPN (1547). Regarding OPN regulation, incubation of VSMC with glucose ranging from 5 to 30 mM (90 -540 mg/dl) resulted in increased release of UTP and UDP (by an unknown mechanism) with a sigmoidal dose response such that essentially the entire reponse occurred in the range of 11.5 mM (207 mg/dl) to 20 mM (360 mg/dl) (1309).…”
Section: E Diabetesmentioning
confidence: 99%