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 125I-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 HF.
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 125I-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 HF.
Authors: Malgorzata Szaroszyk; Badder Kattih; Abel Martin-Garrido; Felix A Trogisch; Gesine M Dittrich; Andrea Grund; Aya Abouissa; Katja Derlin; Martin Meier; Tim Holler; Mortimer Korf-Klingebiel; Katharina Völker; Tania Garfias Macedo; Cristina Pablo Tortola; Michael Boschmann; Nora Huang; Natali Froese; Carolin Zwadlo; Mona Malek Mohammadi; Xiaojing Luo; Michael Wagner; Julio Cordero; Robert Geffers; Sandor Batkai; Thomas Thum; Nadja Bork; Viacheslav O Nikolaev; Oliver J Müller; Hugo A Katus; Ali El-Armouche; Theresia Kraft; Jochen Springer; Gergana Dobreva; Kai C Wollert; Jens Fielitz; Stephan von Haehling; Michaela Kuhn; Johann Bauersachs; Joerg Heineke Journal: Nat Commun Date: 2022-01-10 Impact factor: 14.919
Authors: Gustavo Jose Justo da Silva; Raffaele Altara; George W Booz; Alessandro Cataliotti Journal: Front Physiol Date: 2021-07-08 Impact factor: 4.566