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Complement component C3 as a new target to lower albuminuria in hypertensive kidney disease

Marlies Bode1, Jan Niklas Diemer1, The Vinh Luu1

  • 1III. Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

British Journal of Pharmacology
|April 19, 2023
PubMed

Insights

Complement C3 protein is elevated in hypertensive kidneys. While reducing C3 lowers early-stage albuminuria in hypertension, it does not improve blood pressure or organ damage.

Area of Science:

  • Immunology
  • Nephrology
  • Cardiovascular Research

Background:

  • Complement activation is implicated in hypertension pathogenesis via immune and tissue integrity effects.
  • The central complement protein, C3, plays a key role in the complement cascade.

Purpose of the Study:

  • To investigate the expression of C3 in the context of hypertension.
  • To evaluate the therapeutic potential of targeting C3 in hypertensive models.

Main Methods:

  • Examined C3 expression in kidney biopsies and single-cell RNA sequencing data from hypertensive patients.
  • Utilized angiotensin II (Ang II)-induced and deoxycorticosterone acetate (DOCA)-salt hypertension mouse models.
  • Assessed C3 deficiency (C3-/- mice) and C3 knockdown using siRNA conjugates.

Main Results:

  • Increased C3 expression was observed in kidneys of hypertensive patients and in Ang II-induced hypertension models.
  • C3 deficiency or knockdown significantly reduced albuminuria in the early phase of hypertension in mouse models.
  • No significant improvements in blood pressure, renal injury, or cardiac injury were observed in C3-deficient or knockdown groups.

Conclusions:

  • Elevated C3 expression in the kidneys is associated with hypertension in both humans and mice.
  • Targeting C3 demonstrates potential for mitigating early-stage albuminuria in hypertension.
  • C3 inhibition does not appear to prevent or reverse established hypertension-related renal and cardiac damage.
Abstract

Keywords:
C3DOCA saltalbuminuriaangiotensin IIcardiac damagerenal damage

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