The effects of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor

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Verkleij, Chantal J. N. (author)

The effects of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor

Article/chapterEnglish2009

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2009

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LIBRIS-ID:oai:lup.lub.lu.se:0fb84643-b6bf-46b5-9db1-fcca00791c55
https://lup.lub.lu.se/record/1490256URI
https://doi.org/10.1160/TH09-01-0016DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
protein glycation
cardiovascular disease
diabetes mellitus
TAFI
hyperglycaemia

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Nieuwdorp, Max (author)
Gerdes, Victor E. A. (author)
Mörgelin, MatthiasLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)medk-mmn (author)
Meijers, Joost C. M. (author)
Marx, Pauline F. (author)
InfektionsmedicinSektion III (creator_code:org_t)

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In:Thrombosis and Haemostasis102:3, s. 460-4680340-6245

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