ACE2 alterations in kidney disease

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin (Ang) II to Ang-(1-7). ACE2 is highly expressed within the kidneys, it is largely localized in tubular epithelial cells and less prominently in glomerular epithelial cells and in the renal vasculature. ACE2 activity has been shown to be altered in diabetic kidney disease, hypertensive renal disease and in different models of kidney injury. There is often a dissociation between tubular and glomerular ACE2 expression, particularly in diabetic kidney disease where ACE2 expression is increased at the tubular level but decreased at the glomerular level. In this review, we will discuss alterations in circulating and renal ACE2 recently described in different renal pathologies and disease models as well as their possible significance.

Keywords: ACE2; kidney disease; renin–angiotensin system.

FIGURE 1:

(Upper image) Immunohistochemistry of ACE2 (A and B) in kidney sections from 8-week-old female db/m (A) and db/db mice (B) showing an example of glomerular ACE2 staining. In db/db, ACE2 staining within the glomerular tuft (B, wide arrow) is less intense than in non-diabetic db/m (A, wide arrow). Unlike glomeruli, proximal tubules from db/db mice have more staining for ACE2 (B, narrow arrow) than proximal tubules from db/m (A, narrow arrow). (bar graphs) The percentage of strongly stained glomeruli for ACE2 in 8-week-old db/m (open bar; n = 6) and db/db mice (closed bar; n = 6) (C). Strong ACE2 staining is significantly decreased in glomeruli from diabetic mice in comparison with controls(C). In contrast, kidney cortex ACE2 activity is significantly higher in db/db mice when compared with db/m (D) likely reflecting the increase in ACE2 at the tubular level [compare with (A) and (B)] [adapted from [12] (Panels A, B and C) and [10] (Panel D)]

FIGURE 2:

Podocyte number in WT, podocyte-spcific ACE2 transgenic (TG), wild-type streptozotocin-treated (WT-STZ), and podocyte-specific ACE2 transgenic STZ-treated (TG-STZ) mice at 16 weeks after STZ injection. (A) Graph shows average number of podocytes per glomerulus, as determined by counting of WT-1-positive nuclei in kidney sections. (B) Representative photomicrograph depicting glomerular WT-1 staining in glomeruli from WT-STZ versus TG-STZ mice. Original magnification ×400. Adapted by permission from Macmillan Publishers Ltd: Kidney International (ref 32), copyright (2012).