The effect of class-specific protease inhibitors on the stabilization of B-type natriuretic peptide in human plasma

被引:58
作者
Belenky, A
Smith, A
Zhang, B
Lin, S
Despres, N
Wu, AHB
Bluestein, BI
机构
[1] Bayer Healthcare LLC, Div Diagnost, Lab Testing Segment, Res & Dev, Tarrytown, NY 10591 USA
[2] Hartford Hosp, Dept Pathol & Lab Med, Hartford, CT 06102 USA
关键词
B-type natriuretic peptide; BNP; protease inhibitors; proteolysis; heart failure;
D O I
10.1016/j.cccn.2003.10.026
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Background: B-type natriuretic peptide (BNP) is a cardiac hormone that regulates hemodynamic equilibrium. In the circulation, its activity is controlled by proteolytic factors. Accurate measurement of BNP in a patient's plasma may be affected by degradation due to proteolysis. Objective: We report on the identification and performance of classes of protease inhibitors that stabilize BNP in plasma. Design and methods: Using the Bayer ADVIA Centaur((R)) BNP assay, we measured the effect of arginine, serine and/or specific kallikrein protease inhibitors (PIs) on exogenous spiked or endogenous BNP in patient plasma. Results: Compared to controls without inhibitor, all PIs were capable, to varying degrees, of retarding the rate of proteolytic degradation. The kallikrein-specific inhibitor, D-Phe-Phe-Arg-chloromethylketone (PPACK II) was most effective as a single constituent and was able to eliminate BNP degradation in patient samples for up to 6-10 days when stored at 2-8 degreesC. Conclusions: The stability of BNP was markedly increased in the presence of kallikrein-specific PPACK II and a broad spectrum of serine PIs. Use of these compounds offers a simple method of extending sample handling and storage of plasma samples containing BNP. (C) 2003 Elsevier B.V. All rights reserved.
引用
收藏
页码:163 / 172
页数:10
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