ACE and ACE2 in kidney disease

Abstract

Renin angiotensin system (RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme (ACE)-angiotensin II (Ang II)-Ang II type 1 (AT1) axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang II are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang I and the catabolism of Ang II to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang II-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2.

Emerging Liver–Kidney Interactions in Nonalcoholic Fatty Liver Disease

“…Adipocytes express all RAS components, including angiotensin II (AngII), ACE, renin, and AngII type 1 (AT1) and type 2 (AT2) receptors. In obesity, increased ACE-AngII-AT1 axis activity has been shown to induce organ damage through both autocrine/paracrine and endocrine effects, with adipose tissue contributing up to 30% of systemic circulating AngII ( Figure 1) [4]. The kidney and liver also express all RAS components, and clinical and Trends A growing body of data suggests liverkidney crosstalk in NAFLD, and recent findings have provided insight into the mechanisms underlying this crosstalk.…”

“…In the kidney, ACE-AngII-AT1 activation plays a key role in determining renal ectopic lipid deposition, a hallmark of obesity-associated CKD and a trigger of oxidative stress, inflammation, and fibrogenesis, with both hemodynamic and non-hemodynamic effects, alterations that were all reversed by RAS inhibition (Figure 1) [4,6].…”

“…Accordingly, it is being increasingly recognized that RAS activity depends on the balance between the ACE-AngII-AT 1 receptor and the ACE2-Ang(1-7)-Mas receptor axes, and whose activation is responsible for part of the benefits of RAS blockers [4].…”

Aldosterone effects on glomerular structure and function

“…35 So, it is the balance between ACE and ACE2 that is currently considered critical for the activation of renal RAS. 36,37 Having said that, the second novel aspect of this work is that we show the effect that aldosterone, alone and in combination with salt, has on ACE2 glomerular expression in vivo. Here salt and aldosterone significantly reduced ACE2 expression, while ACE increased, leading to an upregulation of ACE/ACE2 ratio, which is in line with previous observations.…”

New and old agents in the management of diabetic nephropathy

“…In 2000, angiotensin-converting enzyme 2 (ACE2), a type 1 integral membrane protein was identified 4 . ACE2 has almost 40% homology with ACE 4 and is especially abundant in the kidney 5 . ACE2 cleaves the C-terminal amino acid of Ang II to generate the Ang1-7 peptide, which subsequently acts via the Mas receptor to counteract the adverse effects of angiotensin (Ang) II and is thought to provide renoprotection by reducing oxidative stress, inflammation, and lipotoxicity 5 .…”