Left ventricular assist device support reverses altered cardiac expression and function of natriuretic peptides and receptors in end-stage heart failure
Left ventricular assist device support reverses altered cardiac expression and function of natriuretic peptides and receptors in end-stage heart failure
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DOI：
10.1016/j.cardiores.2004.07.004
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发表时间：
2004-11-01
影响因子：
10.8
通讯作者：
Baba, HA
中科院分区：
文献类型：
--
作者：
Kuhn, M;Voss, M;Baba, HA
目的：心房利钠肽（ANP）和b型利钠肽（BNP）通过其环化酶a （GC-A）受体调节动脉血压和血容量，并在心脏发挥局部抗肥厚、抗纤维化和收缩作用。为了阐明心脏肥厚/不全和心脏逆转是否与局部对NPs的反应性变化有关，我们比较了10例充血性心力衰竭（CHF）患者在左心室辅助装置（LVAD）支持下血流动力学卸载前后左心室组织中ANP、BNP和受体的mRNA表达以及GC-A对ANP的反应性。方法和结果：定量实时RT-PCR显示，人衰竭心脏中ANP、BNP及np代谢的NPR-C受体mRNA表达水平均显著升高。GC-A mRNA的表达水平与未衰竭的心脏没有差异，但GC-A对ANP的反应几乎完全消除了cGMP。在LVAD支持期间，心肌细胞肥厚的逆转伴随着ANP、BNP和NPR-C mRNA水平的正常化，以及GC-A对ANP的反应性的显著恢复。结论：在CHF患者中，局部清除nrpr - c受体的增加和心脏GC-A反应性的降低可能会损害利钠肽的局部抗肥厚作用，并导致心脏肥厚和功能不全的进展。LVAD支持期间的反向重塑逆转了这些变化，从而可以恢复ANP和BNP的局部保护作用。(C) 2004欧洲心脏病学会。Elsevier B.V.版权所有。
Objective: Atrial (ANP) and B-type natriuretics peptides (BNP) via their guanylyl cyclase-A (GC-A) receptor not only regulate arterial blood pressure and volume but also exert local antihypertrophic, antifibrotic and lusitropic effects in the heart. To elucidate whether cardiac hypertrophy/insufficiency and reversal is associated with changes in the local responsiveness to NPs, we compared the mRNA expression of ANP, BNP and receptors and the responsiveness of GC-A to ANP in left ventricular tissue obtained from 10 patients with congestive heart failure (CHF) before and after hemodynamic unloading by left ventricular assist device (LVAD) support.Methods and results: Quantitative "real time" RT-PCR demonstrated that the mRNA expression levels of ANP, BNP and the NP-metabolizing NPR-C receptor were both markedly increased in human failing hearts. GC-A mRNA expression levels were not different from nonfailing hearts, but cGMP production by GC-A in response to ANP was nearly abolished. Reversal of cardiomyocyte hypertrophy during LVAD support was accompanied by normalization of ANP, BNP and NPR-C mRNA levels and a significant recovery of GC-A responsiveness to ANP.Conclusion: In CHF patients, increased local clearance by NPR-C receptors and diminished responsiveness of cardiac GC-A might impair the local antihypertrophic effects of natriuretic peptides and contribute to the progression of cardiac hypertrophy and insufficiency. Reverse remodeling during LVAD support reverses these changes and can thereby recuperate the local protective effects of ANP and BNP. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.