Physiological Reports (Jul 2024)

The endocrine basis of the cardio‐renal axis: New perspectives regarding corin

  • Zaid Abassi,
  • Dalit B. Hamo‐Giladi,
  • Safa Kinaneh,
  • Samuel N. Heyman

DOI
https://doi.org/10.14814/phy2.16105
Journal volume & issue
Vol. 12, no. 13
pp. n/a – n/a

Abstract

Read online

Abstract The central role of natriuretic peptides (NPs) in the complex cardio‐renal integrated physiology and organ failure has been revealed over the last four decades. Atrial natriuretic peptide (ANP), the oldest representative of the NPs family, is produced through conversion of proANP to the mature peptide by corin, a trans‐membrane protease localized to the cardiac myocyte membrane. Similarly, brain natriuretic peptide (BNP) is generated by furin, which cleaves proBNP to BNP in myocytes. Though the components of NPs system, their synthesis and target organs are well established, understanding their role in the interplay between the heart and the kidney is steadily evolving. In this context, Feldman et al. (New England Journal of Medicine, 389, 1685) recently described patients with hypertension, cardiomyopathy, atrial arrhythmia and left atrial fibrosis, associated with a homozygous loss‐of‐function variant of the gene encoding corin (Cor−/−). Notably, reduced baseline urinary electrolyte and creatinine excretion have been observed in one of the studied patients. This renal excretory functional impairment could be attributed to the lack of cardiac‐derived ANP in these patients, as implied by Feldman et al. Yet, in this mini‐review we suggest that this aberrant renal manifestation may principally stem from lack of local ANP production at renal tissue, as corin is normally expressed in proximal tubules, Henle's loop and collecting ducts, with locally produced ANP provoking Na+ and water exertion. Collectively, it seems that beside the classic well‐established cardio‐renal axis, the renal NPs system functions as local endocrine machinery in the regulation of sodium excretion.

Keywords