Up-regulation of 'clearance' receptors in patients with chronic heart failure: a possible explanation for the resistance to biological effects of cardiac natriuretic hormones
Up-regulation of 'clearance' receptors in patients with chronic heart failure: a possible explanation for the resistance to biological effects of cardiac natriuretic hormones
复制标题
DOI：
10.1016/s1388-9842(01)00161-1
复制
发表时间：
2001-08-01
影响因子：
18.2
通讯作者：
Giannessi, D
中科院分区：
文献类型：
--
作者：
Andreassi, MG;Del Ry, S;Giannessi, D
背景：迄今为止，心脏利钠肽系统的三种特异性受体已被确定。生物活性结合位点（即NPR-A和NPR-B）的下调可以解释心力衰竭（HF）患者对心脏利钠激素的反应减弱，但不能解释代谢清除率的增加。靶组织中生物和清除（NPR-C）受体之间比例的变化可能解释了这种增加。目的：本研究的目的是探讨心力衰竭患者的血小板上的NPR-C受体的调节。方法：选取18例HF患者（NYHA分类：I-II， n = 8; III-IV, n = 10）和18例年龄匹配的健康受试者。结合位点的亲和力常数（K-d）和密度（B-max）是通过血小板悬浮液中I-125-ANP作为放射配体的饱和度测定得到的。结果：B-max随着疾病严重程度的增加而增加：III-IV类细胞中B-max为21.3 +/- 3.3 fmol/10(9)， I-II类细胞中B-max为11.7 +/- 2.2，对照组中B-max为11.6 +/- 1.1 （III-IV类与对照组相比P = 0.0179，与NYHA I-II相比P = 0.0451）。结论：重型心衰患者“清除”受体密度的增加与心脏利钠肽生物活性的降低以及代谢清除率的增加在理论上是一致的。这表明清除受体阻断可能对HIT有潜在的治疗价值。(C) 2001欧洲心脏病学会。版权所有。
Background: Three specific receptors for the cardiac natriuretic peptide system have been identified to date. Down-regulation of the biologically active binding sites (i.e. NPR-A and NPR-B) could explain the blunted response to cardiac natriuretic hormones observed in heart failure (HF), but not the increased metabolic clearance rate. Variations in the ratio between biological and clearance (NPR-C) receptors in target tissue may explain this increase. Aim: The aim of this study was to investigate the regulation of NPR-C receptors on platelets, in patients with HF. Methods: Eighteen patients with HF (NYHA class: I-II, n = 8; III-IV, n = 10) and 18 age-matched healthy subjects were studied. The affinity constant (K-d) and density (B-max) of binding sites were derived by saturation assays on platelet suspensions using I-125-ANP as radioligand. Results: B-max increased as a function of the severity of disease: 21.3 +/- 3.3 fmol/10(9) cells in class III-IV, 11.7 +/- 2.2 in class I-II, and 11.6 +/- 1.1 in controls, respectively (P = 0.0179 for class III-IV vs. controls and P = 0.0451 vs. NYHA I-II). Conclusions: The increase in density of 'clearance' receptors in severe HF is theoretically consistent with the reduction in cardiac natriuretic peptide biological activity, as well as the increase in metabolic clearance rate. This suggests that clearance receptor blockade may be of potential therapeutic value in HIT. (C) 2001 European Society of Cardiology. All rights reserved.