Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

Hamming, Inge; Timens, Wim; Bulthuis, Marian; Lely, A. Titia; Navis, Gerarda; Goor, Harry van

doi:10.1002/path.1570

Cited by 5,370 publications

(5,836 citation statements)

References 23 publications

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“…ACE2 expression pattern in human kidneys is similar to the one in mouse kidneys, 1,22,27 with primary localization in the proximal tubular epithelium. However, inconsistencies can be found in mouse glomerular ACE2 presence as described even by the same group.…”

Section: Controlsmentioning

confidence: 53%

Renal ACE2 expression and activity is unaltered during established hypertension in adult SHRSP and TGR(mREN2)27

et al. 2009

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Differential renal expression of a homolog of the angiotensin-converting enzyme (ACE), that is, ACE2, has been implicated as a genetic basis of polygenetic hypertension in the stroke-prone spontaneously hypertensive rat model. However, data on the role of ACE2 in hypertension are still inconclusive. Therefore, we analyzed kidney ACE2 mRNA, ACE2 protein and ACE2 enzyme activities in the adult polygenetic stroke-prone spontaneously hypertensive rat (SHRSP) and the monogenetic TGR(mREN2)27 rat models, in comparison with their normotensive reference strains, Wistar-Kyoto (WKY) and Spraque-Dawley (SD) rats, respectively. Kidney ACE2 mRNA was studied using quantitative real-time reverse transcriptase-PCR (RT-PCR) in cortex and medulla, whereas protein expression was scored semiquantitatively in detail in different renal structures using immunohistochemistry. Furthermore, total renal tissue ACE2 activity was measured using a fluorimetric assay that was specified by the ACE2 inhibitor DX600. In SHRSP and homozygous TGR(mREN2)27 rats with established hypertension, kidney ACE2 mRNA, protein and tissue ACE2 activities were not different from their respective WKY and SD reference strain, respectively. In addition, when we looked at renal localization, we found ACE2 protein to be predominantly present in glomeruli and endothelium with weak staining in distal and negative staining in proximal tubuli. Thus, our data challenge previous work that implicates ACE2 as a candidate gene for hypertension in SHRSP by reporting a significant reduction of ACE2 in the kidneys of SHRSP. Taken together, renal ACE2 is not altered in the SHRSP and TGR(mREN2)27 genetic rat models with established hypertension.

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Section: Controlsmentioning

confidence: 53%

Renal ACE2 expression and activity is unaltered during established hypertension in adult SHRSP and TGR(mREN2)27

et al. 2009

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“…In the human lung, immunostaining found that ACE2 was localized to endothelial and smooth muscle cells of large and small blood vessels, as well as type I and II alveolar epithelial cells and bronchial epithelial cells (32,33). In addition to AngI and AngII, ACE2 was found to hydrolyze apelin-13, neurotensin-(1-11), dynorphin A-(1-13), β-casomorphin-(1-7), and ghrelin.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of ACE2 produces antitumor effects via inhibition of angiogenesis and tumor cell invasion in vivo and in vitro

Wan

2011

Oncol Rep

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Abstract. Angiotensin II (AngII) is a multifunctional bioactive peptide in the renin-angiotensin system (RAS). Angiotensinconverting enzyme 2 (ACE2) is a newly identified component of RAS. The role of AngII and ACE2 in the metastasis of non-small cell lung cancer (NSCLC) and the effects on matrix metalloproteinases (MMPs) are still unknown. In the present study, the anti-invasive effect and mechanism of ACE2 were investigated in vitro and in vivo. Results of a transwell assay showed that the overexpression of ACE2 reduces the invasive ability of A549 cells in vitro. According to the results of qRT-PCR and Western blot analysis, the inhibitory role of ACE2 was mediated through the down-regulation of MMP-2 and MMP-9. Additionally, we confirmed that the overexpression of ACE2 inhibited cell growth and VEGFa production while simultaneously suppressing ACE and angiotensin II type 1 receptor (AT1R) expression in human lung cancer xenografts. These results suggest that the overexpression of ACE2 may potentially suppress the invasion and angiogenesis of NSCLC.

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“…It is known that ACE2 is highly expressed in the heart, kidneys, testes, and also in the lungs, in particular (18,19). Alterations in the level of AngII can be seen up to the expression level of ACE2 (20).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Serum Levels of Renin Angiotensin System Components in Asthmatic Patients

Ayada¹,

Toru²,

Genç³

et al. 2015

Erciyes Med J

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Objective: Asthma is a chronic inflammatory lung disease. The renin-angiotensin system (RAS) targets several tissues and maintains fluid homeostasis. It is also known that RAS plays a role in inflammatory processes. Angiotensin-converting enzyme (ACE) and its product angiotensin II (AngII), which are the components of RAS, regulate the known effects of RAS. The other components of RAS, ACE2 and its product Ang 1-7, regulate the counter-effects of RAS. That is why the activation or inhibition of RAS can offer new therapeutic strategies for treating several diseases. We aimed to investigate the serum level of RAS components such as angiotensinogen (AGT), ACE, AngII, ACE2, and Ang 1-7 in asthma and control groups. Materials and Methods:This study was performed on 27 asthma and 23 healthy individuals. The serum levels of AGT, ACE, AngII, ACE2, and Ang 1-7 were measured by human enzyme-linked immunosorbent assay (ELISA) kits.Results: There were no statistically significant differences for the serum levels of AGT and ACE between the groups. The serum levels of AngII, ACE2, and Ang 1-7 were significanlty higher in the asthma group than those in the control group. Conclusion:Our results indicate that two tails of RAS, i.e., the ACE and ACE2 pathways, are activated in asthma compared to are activated more in the asthma group than in the control group. We suppose that the activation of ACE2 tail of RAS occurs because of the homeostatic balance requirements of this system. We believe that the activation of ACE2 pathway, in addition to the inhibition of the ACE pathway, can provide clinical benefits in treating asthma.

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Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

Cited by 5,370 publications

References 23 publications

Renal ACE2 expression and activity is unaltered during established hypertension in adult SHRSP and TGR(mREN2)27

Renal ACE2 expression and activity is unaltered during established hypertension in adult SHRSP and TGR(mREN2)27

Overexpression of ACE2 produces antitumor effects via inhibition of angiogenesis and tumor cell invasion in vivo and in vitro

Evaluation of Serum Levels of Renin Angiotensin System Components in Asthmatic Patients

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