Distinct roles for ANG II and ANG-(1–7) in the regulation of angiotensin-converting enzyme 2 in rat astrocytes

Gallagher, Patricia E.; Chappell, Mark C.; Ferrario, Carlos M.; Tallant, E. Ann

doi:10.1152/ajpcell.00409.2004

Cited by 168 publications

(142 citation statements)

References 54 publications

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“…In contrast, AngII had no effect on ACE mRNA in A549 cells, demonstrating a differential regulation of the two enzymes by AngII. This finding is consistent with tests done in neonatal rat cerebellar and medullary astrocytes (33). Together, these findings demonstrated that AngII can magnify its effect in A549 cells through both decreased ACE2 production and increased AT1-R expression.…”

Section: Discussionsupporting

confidence: 91%

The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer

WAN¹

2010

Oncol Rep

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Abstract. Angiotensin II (AngII) is a multifunctional bioactive peptide and previous studies have shown that the renin-angiotensin system (RAS) of both host and tumor are important in tumor growth and angiogenesis in lung cancer. Angiotensinconverting enzyme 2 (ACE2) is a newly identified component of RAS, with 42% amino acid homology to ACE. However, the expression and function of ACE2 in non-small cell lung cancer (NSCLC) are still unclear. In the present study, we analyzed ACE2 expression in NSCLC tissue by Western blot analysis and immunohistochemistry. AngII concentrations in the tissue homogenate were also detected using radioimmunoassay. We also examined the function of ACE2 by transducing A549 cells with MSCV-ACE2. We have shown for the first time that ACE2 expression decreased in NSCLC tissue in which AngII was higher than the matching nonmalignant tissues. A concentration of 10 -6 mol/l of AngII significantly increased expression of vascular endothelial growth factor a (VEGFa) and AT1-R and decreased ACE2 expression. We also found that overexpression of ACE2 may have a protective effect by inhibiting cell growth and VEGFa production in vitro. ACE2 may become a target of novel strategies to treat NSCLC.

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Section: Discussionsupporting

confidence: 91%

The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer

WAN¹

2010

Oncol Rep

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“…17,30 Although we recently demonstrated that central ACE2 was expressed primarily on neurons, 7 others reported astrocytic expression in vitro. 31 In addition, adenoviral transgenes do not integrate into the genome, therefore preventing random insertional mutagenesis. Although we did not assess inflammation resulting from virus injection, previous work using similar vectors and titers in the brain, 15,27 added to the lack of abnormal behavior in our infected mice, ruled out this possibility.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-Converting Enzyme 2 Overexpression in the Subfornical Organ Prevents the Angiotensin II–Mediated Pressor and Drinking Responses and Is Associated With Angiotensin II Type 1 Receptor Downregulation

Feng

Yue

Xia

et al. 2008

Circulation Research

129

109

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Abstract-We recently reported the presence of angiotensin-converting enzyme (ACE)2 in brain regions controlling cardiovascular function; however, the role of ACE2 in blood pressure regulation remains unclear because of the lack of specific tools to investigate its function. We hypothesized that ACE2 could play a pivotal role in the central regulation of cardiovascular function by regulating other renin-angiotensin system components. To test this hypothesis, we generated an adenovirus expressing the human ACE2 cDNA upstream of an enhanced green fluorescent protein (eGFP) reporter gene . In vitro characterization shows that neuronal cells infected with Ad-hACE2-eGFP (10 to 100 multiplicities of infection), but not Ad-eGFP (100 multiplicities of infection), exhibit dose-dependent ACE2 expression and activity. In addition, an active secreted form was detected in the conditioned medium. In vivo, Ad-hACE2-eGFP infection (2ϫ10 6 plaque-forming units intracerebroventricularly) produced time-dependent expression and activity (with a peak at 7 days) in the mouse subfornical organ. More importantly, 7 days after virus infection, the pressor response to angiotensin (Ang) II (200 pmol intracerebroventricularly) was significantly reduced in Ad-hACE2-eGFP-treated mice compared with controls. Furthermore, subfornical organ-targeted ACE2 overexpression dramatically reduced the Ang II-mediated drinking response. Interestingly, ACE2 overexpression was associated with downregulation of the Ang II type 1 receptor expression both in vitro and in vivo. These data suggest that ACE2 overexpression in the subfornical organ impairs Ang II-mediated pressor and drinking responses at least by inhibiting the Ang II type 1 receptor expression. Taken together, our results show that ACE2 plays a pivotal role in the central regulation of blood pressure and volume homeostasis, offering a new target for the treatment of hypertension and other cardiovascular diseases. (Circ Res. 2008;102:729-736.) Key Words: adenovirus Ⅲ carboxypeptidase Ⅲ brain Ⅲ blood pressure Ⅲ gene therapy T he renin-angiotensin system (RAS) is well known for its effects on the cardiovascular system and fluid homeostasis. Classically, these effects were thought to result primarily from the systemic production of angiotensin (Ang) II. 1 Circulating Ang II stimulates Ang II type 1 (AT 1 ) receptors present in the kidney and the vasculature to produce vasoconstriction but also water and salt reabsorption. Although kidneys and liver are the major endocrine sites of renin and angiotensinogen synthesis, respectively, this view of the RAS has been challenged in the last decade because both genes have been detected in extrarenal and extrahepatic tissues. 2,3 For instance, it has become clear that a local RAS is present in several tissues, for example, the heart, adipose, vasculature, and bone marrow, with similar effects to the endocrine RAS but also more specific functions depending on the individual system. 1 One of these local systems, the brain RAS, has long been considered pivo...

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“…In sharp contrast with these observations are several studies describing a complete or, less frequently, partial inhibition of Ang-(1-7) effects with A-779 , Ferreira et al 2001, Ferrario 2006, Gallagher et al 2006. In some studies a partial blockade was obtained with the AT 2 antagonist PD 123319 when a partial inhibition was also seen with A-779 and the B 2 receptor antagonist Hoe 140.…”

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

confidence: 95%

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

439

369

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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.

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Distinct roles for ANG II and ANG-(1–7) in the regulation of angiotensin-converting enzyme 2 in rat astrocytes

Cited by 168 publications

References 54 publications

The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer

The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer

Angiotensin-Converting Enzyme 2 Overexpression in the Subfornical Organ Prevents the Angiotensin II–Mediated Pressor and Drinking Responses and Is Associated With Angiotensin II Type 1 Receptor Downregulation

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

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