Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular Injury Article

Full Text via DOI: 10.1681/ASN.2016111166 PMID: 28202497 Web of Science: 000404568700018

Cited authors

  • Velez, Juan Carlos Q.; Arif, Ehtesham; Rodgers, Jessalyn; Hicks, Megan P.; Arthur, John M.; Nihalani, Deepak; Bruner, Evelyn T.; Budisavljevic, Milos N.; Atkinson, Carl; Fitzgibbon, Wayne R.; Janech, Michael G.


  • Aminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops. Moreover, BALB/c APA-knockout (KO) mice injected with a nephrotoxic serum showed persistent glomerular hyalinosis and albuminuria 96 hours after injection, whereas wild-type controls achieved virtually full recovery. We then tested the effect of 4-week infusion of AngII (400 ng/kg per minute) in APA-KO and wild-type mice. Although we observed no significant difference in achieved systolic BP, AngII-treated APA-KO mice developed a significant rise in albuminuria not observed in AngII-treated wild-type mice along with increased segmental and global sclerosis and/or collapse of juxtamedullary glomeruli, microcystic tubular dilation, and tubulointerstitial fibrosis. In parallel, AngII treatment significantly increased the kidney AngII content and attenuated the expression of podocyte nephrin in APA-KO mice but not in wild-type controls. These data show that deficiency of APA increases susceptibility to glomerular injury in BALB/c mice. The augmented AngII-mediated kidney injury observed in association with increased intrarenal AngII accumulation in the absence of APA suggests a protective metabolizing role of APA in AngII-mediated glomerular diseases.

Publication date

  • 2017

International Standard Serial Number (ISSN)

  • 1046-6673

Start page

  • 2119

End page

  • 2132


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