Clinical implications of defective B-type natriuretic peptide.
Clinical implications of defective B-type natriuretic peptide.
复制标题
DOI：
10.1002/clc.20480
复制
发表时间：
2009-12-01
影响因子：
2.7
通讯作者：
Protter, Andrew A
中科院分区：
文献类型：
--
作者：
Menon, Santosh G;Mills, Roger M;Protter, Andrew A
我们对利钠肽系统的理解继续迅速发展。B型利钠肽（BNP）最初被认为是一种简单的容量调节激素，在心脏牵张时产生，已被证明在调节支气管扩张、内皮功能和心脏重塑中也起重要作用。最近的数据表明，心力衰竭患者BNP水平升高并不代表正常生产的简单增加，以响应增加的刺激。相反，我们现在知道，BNP合成的慢性刺激诱导胎儿基因表达的逆转，导致功能缺陷的高分子量形式的BNP的产生。标准床旁BNP测定是将检测含有靶表位的任何分子的免疫测定。因此，这些测定不能区分有缺陷的高分子量形式的BNP和正常的生理活性BNP。在2项单独的评价中，质谱法在心力衰竭患者中检测到很少（如果有的话）正常BNP，尽管使用商业测定法出现高循环水平的免疫反应性BNP（iBNP）。因此，这些商业测定应被认为仅是心肌应激的指示。它们不测量生理BNP活性。这解释了"BNP悖论"，即使用商业测定，在存在高水平循环iBNP的情况下，外源性重组人BNP（rhBNP，奈西立肽）的给药具有显著的临床和血液动力学影响。除了短期血流动力学影响外，rhBNP在这种情况下可能具有其他重要作用，需要进一步研究。
Our understanding of the natriuretic peptide system continues to evolve rapidly. B-type natriuretic peptide (BNP), originally thought to be a simple volume-regulating hormone that is produced in response to cardiac stretch, has been shown to also play important roles in modulating bronchodilation, endothelial function, and cardiac remodeling. Recent data demonstrate that elevated levels of BNP in patients with heart failure do not represent a simple ratcheting up of normal production in response to increased stimulus. Instead, we now know that chronic stimulation of BNP synthesis induces a reversion to fetal gene expression, resulting in production of high molecular weight forms of BNP that are functionally deficient. Standard point-of-care BNP assays are immunoassays that will detect any molecule containing the target epitopes. Consequently, these assays cannot distinguish between defective, high molecular weight forms of BNP and normal, physiologically active BNP. In 2 separate evaluations, mass spectroscopy detected little, if any, normal BNP in patients with heart failure, despite the appearance of high circulating levels of immunoreactive BNP (iBNP) using commercial assays. Therefore, these commercial assays should be considered to be only an indication of myocardial stress. They do not measure physiologic BNP activity. This accounts for the "BNP paradox," namely, that administration of exogenous recombinant human BNP (rhBNP, nesiritide) has substantial clinical and hemodynamic impact in the presence of high levels of circulating iBNP using commercial assays. In addition to its short-term hemodynamic impact, rhBNP may have other important effects in this setting, and further investigation is warranted.