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The Oxidative Modification of Von Willebrand Factor Is Associated with Thrombotic Angiopathies in Diabetes Mellitus

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 diabete...

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Autores principales: Oggianu, Laura, Lancellotti, Stefano, Pitocco, Dario, Zaccardi, Francesco, Rizzo, Paola, Martini, Francesca, Ghirlanda, Giovanni, De Cristofaro, Raimondo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561310/
https://www.ncbi.nlm.nih.gov/pubmed/23383177
http://dx.doi.org/10.1371/journal.pone.0055396
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author Oggianu, Laura
Lancellotti, Stefano
Pitocco, Dario
Zaccardi, Francesco
Rizzo, Paola
Martini, Francesca
Ghirlanda, Giovanni
De Cristofaro, Raimondo
author_facet Oggianu, Laura
Lancellotti, Stefano
Pitocco, Dario
Zaccardi, Francesco
Rizzo, Paola
Martini, Francesca
Ghirlanda, Giovanni
De Cristofaro, Raimondo
author_sort Oggianu, Laura
collection PubMed
description 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 type 1 and 42 type 2 diabetic subjects) and their respective eighty-three healthy controls were studied after verifying the availability, through institutional databases, of clinical biochemistry records spanning at least 3 years. VWF and protein carbonyls were measured by immunoassays, whereas VWF multimers were studied by SDS-agarose gel electrophoresis. Type 2 diabetic subjects had higher levels of VWF antigen (VWF:ag), VWF activity (VWF:act) and plasma proteins’ carbonyls compared to both their controls and type 1 diabetic subjects. Moreover, high molecular weight VWF multimers and specific VWF-bound carbonyls were significantly increased in subjects with micro- and macro-angiopathic complications. In both type 1 and type 2 diabetic subjects, ADAMTS-13 activity was in the normal range. In a multivariable analysis, only VWF-bound carbonyls were significantly associated with any form of thrombotic angiopathy in the entire group of T1- and T2 diabetic patients. These data provide first evidence that not only high VWF levels but also its oxidation status and the presence of high molecular weight VWF multimers that are not observed in SDS-agarose gel electrophoresis of normal subjects are associated with thrombotic angiopathies in diabetes mellitus. These findings may help identify diabetic patients particularly at risk for these complications and elucidate a new pathophysiological mechanism of thrombotic angiopathies in this clinical setting.
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spelling pubmed-35613102013-02-04 The Oxidative Modification of Von Willebrand Factor Is Associated with Thrombotic Angiopathies in Diabetes Mellitus Oggianu, Laura Lancellotti, Stefano Pitocco, Dario Zaccardi, Francesco Rizzo, Paola Martini, Francesca Ghirlanda, Giovanni De Cristofaro, Raimondo PLoS One Research Article 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 type 1 and 42 type 2 diabetic subjects) and their respective eighty-three healthy controls were studied after verifying the availability, through institutional databases, of clinical biochemistry records spanning at least 3 years. VWF and protein carbonyls were measured by immunoassays, whereas VWF multimers were studied by SDS-agarose gel electrophoresis. Type 2 diabetic subjects had higher levels of VWF antigen (VWF:ag), VWF activity (VWF:act) and plasma proteins’ carbonyls compared to both their controls and type 1 diabetic subjects. Moreover, high molecular weight VWF multimers and specific VWF-bound carbonyls were significantly increased in subjects with micro- and macro-angiopathic complications. In both type 1 and type 2 diabetic subjects, ADAMTS-13 activity was in the normal range. In a multivariable analysis, only VWF-bound carbonyls were significantly associated with any form of thrombotic angiopathy in the entire group of T1- and T2 diabetic patients. These data provide first evidence that not only high VWF levels but also its oxidation status and the presence of high molecular weight VWF multimers that are not observed in SDS-agarose gel electrophoresis of normal subjects are associated with thrombotic angiopathies in diabetes mellitus. These findings may help identify diabetic patients particularly at risk for these complications and elucidate a new pathophysiological mechanism of thrombotic angiopathies in this clinical setting. Public Library of Science 2013-01-31 /pmc/articles/PMC3561310/ /pubmed/23383177 http://dx.doi.org/10.1371/journal.pone.0055396 Text en © 2013 Oggianu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Oggianu, Laura
Lancellotti, Stefano
Pitocco, Dario
Zaccardi, Francesco
Rizzo, Paola
Martini, Francesca
Ghirlanda, Giovanni
De Cristofaro, Raimondo
The Oxidative Modification of Von Willebrand Factor Is Associated with Thrombotic Angiopathies in Diabetes Mellitus
title The Oxidative Modification of Von Willebrand Factor Is Associated with Thrombotic Angiopathies in Diabetes Mellitus
title_full The Oxidative Modification of Von Willebrand Factor Is Associated with Thrombotic Angiopathies in Diabetes Mellitus
title_fullStr The Oxidative Modification of Von Willebrand Factor Is Associated with Thrombotic Angiopathies in Diabetes Mellitus
title_full_unstemmed The Oxidative Modification of Von Willebrand Factor Is Associated with Thrombotic Angiopathies in Diabetes Mellitus
title_short The Oxidative Modification of Von Willebrand Factor Is Associated with Thrombotic Angiopathies in Diabetes Mellitus
title_sort oxidative modification of von willebrand factor is associated with thrombotic angiopathies in diabetes mellitus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561310/
https://www.ncbi.nlm.nih.gov/pubmed/23383177
http://dx.doi.org/10.1371/journal.pone.0055396
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