ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice

M. J. Soler, Jan Wysocki, M. Ye, J. Lloveras, Yashpal S Kanwar, Daniel Batlle*

*Corresponding author for this work

Research output: Contribution to journalArticle

150 Scopus citations

Abstract

Angiotensin converting enzyme 2 (ACE2) is localized to the glomerular epithelial cells. Since ACE2 promotes the degradation of angiotensin II, a decrease in ACE2 activity could lead to the development of glomerular injury. We gave a specific ACE2 inhibitor, MLN-4760, for 4 weeks to mice rendered diabetic with streptozotocin. The urinary albumin/creatinine ratio was increased along with expansion of the glomerular matrix in diabetic mice treated with the inhibitor compared to the vehicle-treated mice. Glomerular staining of ACE was increased in the diabetic group and was further significantly increased in the diabetic group treated with MLN-4760. In renal vessels, ACE expression was also increased in the diabetic mice and, again, further increased in those diabetic mice treated with the ACE2 inhibitor. Our study shows that chronic pharmacologic ACE2 inhibition worsens glomerular injury in streptozotocin-induced diabetic mice in association with increased ACE expression.

Original languageEnglish (US)
Pages (from-to)614-623
Number of pages10
JournalKidney international
Volume72
Issue number5
DOIs
StatePublished - Jan 1 2007

Keywords

  • ACE
  • ACE2
  • ACE2 inhibition
  • Albuminuria
  • Diabetic nephropathy
  • Renal histology

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice'. Together they form a unique fingerprint.

  • Cite this