ACE2 gene expression is up-regulated in the human failing heart

Goulter, Andrew B.; Goddard, Martin; Allen, Jonathan; Clark, Kenneth L.

doi:10.1186/1741-7015-2-19

Cited by 216 publications

(192 citation statements)

References 18 publications

Supporting

Mentioning

179

Contrasting

Unclassified

Order By: Relevance

“…Yet, our data do not completely rule out a possible contribution to specific hypertensive conditions such as Sabra rat model, or an important (protective) role for tissue ACE2 at local organ-specific sites. 28,[32][33][34][35] In conclusion, kidney ACE2 expression and activity is similar in polygenetic and monogenetic adult rat models of hypertension as compared with their normotensive reference strains. The precise role of renal ACE2 in hypertension remains to be established.…”

Section: Controlsmentioning

confidence: 78%

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

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

Section: Controlsmentioning

confidence: 78%

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

et al. 2009

View full text Add to dashboard Cite

show abstract

“…[5][6][7][8][9] In addition, ACE inhibitors and AngII type 1 receptor antagonists, which have proven beneficial for the treatment of MI and HF, increase ACE2 gene expression, attenuate ACE2 gene downregulation, and normalize AngII type 1 receptor expression in the myocardium post-MI. 6,10,16,17 Taken together, these observations suggest that the increase of ACE2 expression in the myocardium is because of a compensatory mechanism to cardiac dysfunction and also is responsible, at least in part, to the cardioprotective and beneficial outcomes observed with the use of Ang pathway inhibitors during treatment of MI and HF.…”

Section: Discussionmentioning

confidence: 99%

“…4 Second, ACE2 expression is increased in the myocardium after coronary artery ligation (CAL), 5,6 in addition to an increase in activity in failing human hearts. [7][8][9] Third, the major product of ACE2, Ang(1-7), produces beneficial outcomes on cardiac function (ie, coronary perfusion, endothelial function, and contractility) 10,11 and attenuates development of HF postischemia. 11,12 Fourth, overexpression of ACE2 protects the heart from hypertension-induced cardiac pathophysiology (ie, hypertrophy and fibrosis) [12][13][14] and inhibits hypoxia-induced collagen production by cardiac fibroblasts.…”

mentioning

confidence: 99%

Cardiac Overexpression of Angiotensin Converting Enzyme 2 Protects the Heart From Ischemia-Induced Pathophysiology

et al. 2008

View full text Add to dashboard Cite

Abstract-Angiotensin converting enzyme 2 (ACE2) has been linked to cardiac dysfunction and hypertension-induced cardiac pathophysiology. In this study, we used a gene overexpression approach to investigate the role of ACE2 in cardiac function and remodeling after myocardial infarction. Rats received an intracardiac injection of 4.5ϫ10 8 lentivirus containing ACE2 cDNA, followed by permanent coronary artery ligation (CAL) of the left anterior descending artery. At 24 hours and 6 weeks after surgery, cardiac functions, viability, and pathophysiology were assessed by MRI) and by histological analysis. At 24 hours post-CAL, left ventricular (LV) anterior wall motion was stunted to the same extent in control CAL and lenti-ACE2-treated CAL rats. However lenti-ACE2-treated CAL rats showed a 60% reduction in delayed contrast-enhanced LV volume after gadodiamide injection, indicating early ischemic protection of myocardium by ACE2. At 6 weeks after CAL, lenti-ACE2 rats demonstrated a complete rescue of cardiac output, a 41% rescue of ejection fraction, a 44% rescue in contractility, a 37% rescue in motion, and a 53% rescue in LV anterior (infracted) wall thinning compared with control CAL rats. No changes were observed in the LV posterior (noninfarcted) wall other than an 81% rescue in motion produced by ACE2 in CAL rats. Finally, infarct size measured by 2,3,5-triphenyl-tetrazolium chloride staining was not significantly different between the ligated groups. These observations demonstrate that cardiac overexpression of ACE2 exerts protective influence on the heart during myocardial infarction by preserving cardiac functions, LV wall motion and contractility, and by attenuating LV wall thinning. (Hypertension. 2008;51:712-718.)

show abstract

“…However, it should be stressed that the role of ACE2 in heart function and structure might depend on the species . Interestingly, ACE2 expression has been reported to be increased in failing human heart ventricle (Zisman et al 2003, Goulter et al 2004, Burrell et al 2005. Nevertheless, there are contrasting findings in rat hearts.…”

Section: Cardiac Actions Of the Ace2/ang-(1-7)/mas Axismentioning

confidence: 99%

Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

Santos

Ferreira

Verano‐Braga

et al. 2012

Journal of Endocrinology

430

369

View full text Add to dashboard Cite

Angiotensin (Ang)-(1-7) is now recognized as a biologically active component of the reninangiotensin system (RAS). Ang-(1-7) appears to play a central role in the RAS because it exerts a vast array of actions, many of them opposite to those attributed to the main effector peptide of the RAS, Ang II. The discovery of the Ang-converting enzyme (ACE) homolog ACE2 brought to light an important metabolic pathway responsible for Ang-(1-7) synthesis. This enzyme can form Ang-(1-7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation by ACE. In addition, it is now well established that the G protein-coupled receptor Mas is a functional binding site for Ang-(1-7). Thus, the axis formed by ACE2/Ang-(1-7)/Mas appears to represent an endogenous counterregulatory pathway within the RAS, the actions of which are in opposition to the vasoconstrictor/ proliferative arm of the RAS consisting of ACE, Ang II, and AT 1 receptor. In this brief review, we will discuss recent findings related to the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular and renal systems, as well as in metabolism. In addition, we will highlight the potential interactions of Ang-(1-7) and Mas with AT 1 and AT 2 receptors.

show abstract

ACE2 gene expression is up-regulated in the human failing heart

Cited by 216 publications

References 18 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

Cardiac Overexpression of Angiotensin Converting Enzyme 2 Protects the Heart From Ischemia-Induced Pathophysiology

Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

Contact Info

Product

Resources

About