Plasma levels of carboxypeptidase U (CPU, CPB2 or TAFIa) are elevated in patients with acute myocardial infarction
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Medicine and Health Sciences
Journal of thrombosis and haemostasis. - Oxford
, p. 2227-2232
University of Antwerp
Background Two decades after its discovery, carboxypeptidase U (CPU, CPB2 or TAFIa) has become a compelling drug target in thrombosis research. However, given the difficulty of measuring CPU in the blood circulation and the demanding sample collecton requirements, previous clinical studies focused mainly on measuring its inactive precursor, proCPU (proCPB2 or TAFI). Objectives Using a sensitive and specific enzymatic assay, we investigated plasma CPU levels in patients presenting with acute myocardial infarction (AMI) and in controls. Methods In this casecontrol study, peripheral arterial blood samples were collected from 45 patients with AMI (25 with ST segment elevation myocardial infarction [STEMI], 20 with non-ST segment elevation myocardial infarction [NSTEMI]) and 42 controls. Additionally, intracoronary blood samples were collected from 11 STEMI patients during thrombus aspiration. Subsequently, proCPU and CPU plasma concentrations in all samples were measured by means of an activity-based assay, using Bz-o-cyano-Phe-Arg as a selective substrate. Results CPU activity levels were higher in patients with AMI (median LOD-LOQ, range 01277 mU L−1) than in controls (median < LOD, range 0128 mU L−1). No correlation was found between CPU levels and AMI type (NSTEMI [median between LOD-LOQ, range 0465 mU L−1] vs. STEMI [median between LOD-LOQ, range 01277 mU L−1]). Intracoronary samples (median 109 mU L−1, range 0759 mU L−1) contained higher CPU levels than did peripheral samples (median between LOD-LOQ, range 0107 mU L−1), indicating increased local CPU generation. With regard to proCPU, we found lower levels in AMI patients (median 910 U L−1, range 7061224 U L−1) than in controls (median 1010 U L−1, range 7531396 U L−1). Conclusions AMI patients have higher plasma CPU levels and lower proCPU levels than controls. This finding indicates in vivo generation of functional active CPU in patients with AMI.