Severe heart failure (NYHA class III-IV) was associated with increased density of NPR-C clearance receptors on platelets compared to healthy controls (21.3 vs 11.6 fmol/10^9 cells; P=0.0179).
Case-Control (n=36)
Is the density of NPR-C clearance receptors on platelets increased in patients with chronic heart failure compared to healthy subjects?
The up-regulation of natriuretic peptide clearance receptors in severe heart failure provides a mechanistic explanation for the resistance to the biological effects of cardiac natriuretic hormones.
Absolute Event Rate: 21.3% vs 11.6%
p-value: p=0.0179
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.
Andreassi et al. (Wed,) conducted a case-control in Chronic Heart Failure (n=36). Heart failure vs. Healthy subjects was evaluated on Density (B(max)) of binding sites on platelets (p=0.0179). Severe heart failure (NYHA class III-IV) was associated with increased density of NPR-C clearance receptors on platelets compared to healthy controls (21.3 vs 11.6 fmol/10^9 cells; P=0.0179).