Plasma Procarboxypeptidase U in Men with Symptomatic Coronary Artery Disease

Angela Silveira; Katinka Schatteman; Filip Goossens; Elisabeth Moor; Simon Scharpé; Mats Strömqvist; Dirk Hendriks; Anders Hamsten

doi:10.1055/s-0037-1614029

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2000; 84(03): 364-368
DOI: 10.1055/s-0037-1614029

Commentary

Schattauer GmbH

Plasma Procarboxypeptidase U in Men with Symptomatic Coronary Artery Disease

Angela Silveira

¹From the King Gustaf V Research Institute, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden

,

Katinka Schatteman

³Department of Medical Biochemistry, University of Antwerp, Antwerp, Belgium

,

Filip Goossens

³Department of Medical Biochemistry, University of Antwerp, Antwerp, Belgium

,

Elisabeth Moor

²The Department of Cardiology, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden

,

Simon Scharpé

³Department of Medical Biochemistry, University of Antwerp, Antwerp, Belgium

,

Mats Strömqvist

⁴Molecular Biology, AstraZeneca R&D, Mölndal, Sweden

,

Dirk Hendriks

³Department of Medical Biochemistry, University of Antwerp, Antwerp, Belgium

,

Anders Hamsten

¹From the King Gustaf V Research Institute, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden

²The Department of Cardiology, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden

› Institutsangaben

Abstract

Summary

Procarboxypeptidase U (proCPU) is the plasma precursor of carboxypeptidase U (CPU, carboxypeptidase R, plasma carboxypeptidase B or activated thrombin-activatable fibrinolysis inhibitor, TAFIa). CPU removes C-terminal lysine residues that act as plasminogen binding sites from partially degraded fibrin, thereby down-regulating plasminogen activation and fibrinolysis. The present study was carried out as a pilot study to examine whether the plasma proCPU concentration is related to the presence of coronary artery disease (CAD) and/or to levels of established risk indicators for CAD, in a case-control study of 110 men requiring coronary artery bypass grafting (CABG) because of stable angina pectoris. The preoperative plasma proCPU level in the CABG patients was significantly higher than in population-based controls (1029 ± 154 vs. 974 ± 140 U/L, p <0.05). In addition, in a subset of the patients (n = 31) the proCPU concentration, which was significantly lower on the third postoperative day (−17 ± 10%), had increased significantly on the sixth day (+14 ± 12%) after surgery, compared with the preoperative level. In both patients and controls, proCPU concentration was strongly and positively associated with factor VII amidolytic activity and protein C activity, suggesting a common mechanism modulating the plasma levels of these proteins. Otherwise, statistically significant correlations with proCPU were group-specific. In the patients, proCPU correlated significantly with plasma fibrinogen and protein S. In the controls, proCPU correlated significantly with concentrations of cholesterol in plasma, VLDL and LDL. In addition, proCPU correlated significantly with C-reactive protein and haptoglobin levels in the controls only, indicating that also inflammatory mechanisms are involved in the regulation of plasma proCPU. These results suggest that a mechanism exists by which fibrinolytic function is impaired in a manner that is likely to result in more stable fibrin deposits and increase the risk of precocious CAD as well as early occlusion of venous bypass grafts.

Key words

Procarboxypeptidase U - TAFI - coronary artery disease - bypass surgery - fibrinolysis

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Referenzen

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