The effects of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor
(2009) In Thrombosis and Haemostasis 102(3). p.460-468- Abstract
- Epidemiological studies have shown a strong association between type 2 diabetes mellitus and cardiovascular diseases, and hypofibrinolysis may contribute to this phenomenon. The aim of this study was to determine the effect of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor (TAR). Hyperglycaemia was mimicked in vitro by incubation of TAFI with glyceraldehyde and in vivo by hyperglycaemic clamping of healthy volunteers. The effects of long-term hyperglycaemia in vivo on TAR were investigated by comparing TAFI from poorly regulated and tightly regulated patients with type 2 diabetes. In vitro glycated TAR showed an altered migration pattern on SDS-PAGE due to aggregation. Glycated TAFI showed decreased activity after activation... (More)
- Epidemiological studies have shown a strong association between type 2 diabetes mellitus and cardiovascular diseases, and hypofibrinolysis may contribute to this phenomenon. The aim of this study was to determine the effect of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor (TAR). Hyperglycaemia was mimicked in vitro by incubation of TAFI with glyceraldehyde and in vivo by hyperglycaemic clamping of healthy volunteers. The effects of long-term hyperglycaemia in vivo on TAR were investigated by comparing TAFI from poorly regulated and tightly regulated patients with type 2 diabetes. In vitro glycated TAR showed an altered migration pattern on SDS-PAGE due to aggregation. Glycated TAFI showed decreased activity after activation by thrombin-thrombomodulin in a glyceraldehyde-dose-dependent manner and a reduced anti-fibrinolytic potential. In vivo, no differences in TAR parameters were found after hyperglycaemic clamping of healthy volunteers and between tightly and poorly regulated patients with type 2 diabetes. Moreover, TAR purified from poorly regulated and tightly regulated patients with type 2 diabetes migrated similarly on SDS-PAGE, indicating little or no glycation of the protein. Despite the deleterious effects of glycation of TAR in vitro on its function,TAFI was neither affected by hyperglycaemic clamping, nor by long-term hyperglycaemia in patients with type 2 diabetes. This is in contrast to fibrinolytic factors as plasminogen-activator inhibitor I and tissue-type plasminogen activator, which are affected. We therefore hypothesise that a normally functioning TAR under hyperglycaemic conditions may tip the haemostatic balance towards hypofibrinolysis, which may contribute to the development of cardiovascular diseases in type 2 diabetic patients. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1490256
- author
- Verkleij, Chantal J. N. ; Nieuwdorp, Max ; Gerdes, Victor E. A. ; Mörgelin, Matthias LU ; Meijers, Joost C. M. and Marx, Pauline F.
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- protein glycation, cardiovascular disease, diabetes mellitus, TAFI, hyperglycaemia
- in
- Thrombosis and Haemostasis
- volume
- 102
- issue
- 3
- pages
- 460 - 468
- publisher
- Schattauer GmbH
- external identifiers
-
- wos:000269890200007
- scopus:70449338765
- pmid:19718465
- ISSN
- 0340-6245
- DOI
- 10.1160/TH09-01-0016
- language
- English
- LU publication?
- yes
- id
- 0fb84643-b6bf-46b5-9db1-fcca00791c55 (old id 1490256)
- date added to LUP
- 2016-04-01 14:08:35
- date last changed
- 2022-01-27 22:55:56
@article{0fb84643-b6bf-46b5-9db1-fcca00791c55,
abstract = {{Epidemiological studies have shown a strong association between type 2 diabetes mellitus and cardiovascular diseases, and hypofibrinolysis may contribute to this phenomenon. The aim of this study was to determine the effect of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor (TAR). Hyperglycaemia was mimicked in vitro by incubation of TAFI with glyceraldehyde and in vivo by hyperglycaemic clamping of healthy volunteers. The effects of long-term hyperglycaemia in vivo on TAR were investigated by comparing TAFI from poorly regulated and tightly regulated patients with type 2 diabetes. In vitro glycated TAR showed an altered migration pattern on SDS-PAGE due to aggregation. Glycated TAFI showed decreased activity after activation by thrombin-thrombomodulin in a glyceraldehyde-dose-dependent manner and a reduced anti-fibrinolytic potential. In vivo, no differences in TAR parameters were found after hyperglycaemic clamping of healthy volunteers and between tightly and poorly regulated patients with type 2 diabetes. Moreover, TAR purified from poorly regulated and tightly regulated patients with type 2 diabetes migrated similarly on SDS-PAGE, indicating little or no glycation of the protein. Despite the deleterious effects of glycation of TAR in vitro on its function,TAFI was neither affected by hyperglycaemic clamping, nor by long-term hyperglycaemia in patients with type 2 diabetes. This is in contrast to fibrinolytic factors as plasminogen-activator inhibitor I and tissue-type plasminogen activator, which are affected. We therefore hypothesise that a normally functioning TAR under hyperglycaemic conditions may tip the haemostatic balance towards hypofibrinolysis, which may contribute to the development of cardiovascular diseases in type 2 diabetic patients.}},
author = {{Verkleij, Chantal J. N. and Nieuwdorp, Max and Gerdes, Victor E. A. and Mörgelin, Matthias and Meijers, Joost C. M. and Marx, Pauline F.}},
issn = {{0340-6245}},
keywords = {{protein glycation; cardiovascular disease; diabetes mellitus; TAFI; hyperglycaemia}},
language = {{eng}},
number = {{3}},
pages = {{460--468}},
publisher = {{Schattauer GmbH}},
series = {{Thrombosis and Haemostasis}},
title = {{The effects of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor}},
url = {{http://dx.doi.org/10.1160/TH09-01-0016}},
doi = {{10.1160/TH09-01-0016}},
volume = {{102}},
year = {{2009}},
}