A Place in Our Hearts for the Lowly Angiotensin 1-7 Peptide?

Reudelhuber, Timothy L.

doi:10.1161/01.hyp.0000209020.69734.73

Cited by 36 publications

(31 citation statements)

References 36 publications

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“…15 ). Research concerning its biological properties took on new importance with the demonstration that its concentration greatly increased with ACE inhibition and angiotensin receptor blockade 16 and the identification of an enzyme (ACE2; Figure 1) that mediates its direct synthesis from Ang II. 17 Because most of the properties of Ang-(1-7) were demonstrated either in vitro or in acute infusions, we used the peptide-targeting strategy to examine the chronic in vivo effects of this interesting peptide.…”

Section: Ang IV In the Brainmentioning

confidence: 99%

Deciphering the Roles of Tissue Renin-Angiotensin Systems in Whole Animals

Reudelhuber

2011

Hypertension

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Section: Ang IV In the Brainmentioning

confidence: 99%

Deciphering the Roles of Tissue Renin-Angiotensin Systems in Whole Animals

Reudelhuber

2011

Hypertension

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“…This conversion is efficiently catalyzed by the recently discovered ACE homologue, ACE2 [19]. Yet, hydrolysis of Ang II by ACE2 is inferior to binding to its receptor, which has a three orders of magnitude higher affinity [20].…”

Section: Introductionmentioning

confidence: 99%

ACE2 of the heart: From angiotensin I to angiotensin (1–7)

Keidar

Kaplan

Gamliel-Lazarovich

2007

Cardiovascular Research

240

184

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Angiotensin II (Ang II), a bioactive peptide of the renin-angiotensin system (RAAS), plays an important role in the development of cardiovascular diseases (CVD). Pharmacological inhibition of angiotensin-converting enzyme (ACE), the Ang II forming enzyme, or specific blockade of Ang II binding to angiotensin type 1 receptor (AT1R) through which it exerts its deleterious effects, were shown to provide some protection against progression of CVD. The ACE-Ang II-AT1R axis has been challenged over the last few years with RAAS components able to counterbalance the effects of the main axis. The ACE homologue ACE2 efficiently hydrolyses Ang II to form Ang (1-7), a peptide that exerts actions opposite to those of Ang II. In contrast to the Ang II axis, the role of the ACE2-Ang (1-7) axis in cardiac function is largely obscure. Ang (1-7) is present in the viable myocardium, and its formation depends on Ang II as a substrate. The expression of this peptide is associated with cardiac remodeling: it is lost in the infarcted area and significantly increased in the border area. Low doses of Ang (1-7) improve cardiac output and antagonize Ang II-induced vasoconstriction. The type of Ang (1-7) biological activity is tissue specific and dose dependent. These findings point to a possible protective role for Ang (1-7) in abating the Ang II-induced actions. The elevated expression of Ang (1-7) in failing heart tissue paralleled the expression of its forming enzyme, ACE2. Several observations and experimental evidence suggest a beneficial role for ACE2 in cardiovascular function. Elevated ACE2 expression at the initial stage of several pathologies which decline with progression of disease might indicate a protective role for ACE2. Genetic manipulation of ACE2 expression, either targeted disruption or overexpression, point to the possible significance of this enzyme in cardiac function. Based on the above, a therapeutic approach that will amplify the ACE2-Ang (1-7) axis could provide further protection against the development of CVD. It turns out that the merits of currently used drugs--ACE inhibitors, AT1R blockers and mineralocorticoid receptor blockers (MRB) - lay beyond their direct effects on suppression of the ACE-Ang II-AT1R axis as they also increase cardiac ACE2 and Ang (1-7) significantly.

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“…In addition to Ang- (1)(2)(3)(4)(5)(6)(7) and its receptor Mas, the recently described homologue of ACE, ACE2 may form the ACE 2-Ang-(1-7)-Mas axis (12,13). This axis induces opposite effects to those elicited by the classical ACE-Ang II-ATR axis (12,14). Ang- (1)(2)(3)(4)(5)(6)(7) shows protective effects in myocardial infarction (15), diabetes-induced cardiovascular dysfunctions (16) and hepatic fibrosis (17).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Targets in Liver Transplantation: Angiotensin II in Nonsteatotic Grafts and Angiotensin-(1—7) in Steatotic Grafts

Alfany-Fernandez

Casillas-Ramírez

Bintanel-Morcillo

et al. 2009

American Journal of Transplantation

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This work was supported by the Ministerio de Educación y Ciencia (project grant SAF 2005-00385) (Madrid, Spain), Ministerio de Sanidad y Consumo (project grant PIO60021) (Madrid, Spain) Numerous steatotic livers are discarded as unsuitable for transplantation because of their poor tolerance of ischemia-reperfusion(I/R). The injurious effects of angiotensin (Ang)-II and the benefits of Ang-(1-7) in various pathologies are well documented. We examined the generation of Ang II and Ang-(1-7) in steatotic and nonsteatotic liver grafts from Zucker rats following transplantation. We also studied in both liver grafts the effects of Ang-II receptors antagonists and Ang-(1-7) receptor antagonists on hepatic I/R damage associated with transplantation. Nonsteatotic grafts showed higher Ang II levels than steatotic grafts, whereas steatotic grafts showed higher Ang-(1-7) levels than nonsteatotic grafts. Ang II receptor antagonists protected only nonsteatotic grafts against damage, whereas Ang-(1-7) receptor antagonists were effective only in steatotic grafts. The protection conferred by Ang II receptor antagonists in nonsteatotic grafts was associated with ERK 1/2 overexpression, whereas the beneficial effects of Ang-(1-7) receptor antagonists in steatotic grafts may be mediated by NO inhibition. Our results show that Ang II receptor antagonists are effective only in nonsteatotic liver transplantation and point to a novel therapeutic target in liver transplantation based on Ang-(1-7), which is specific for steatotic liver grafts.

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A Place in Our Hearts for the Lowly Angiotensin 1-7 Peptide?

Cited by 36 publications

References 36 publications

Deciphering the Roles of Tissue Renin-Angiotensin Systems in Whole Animals

Deciphering the Roles of Tissue Renin-Angiotensin Systems in Whole Animals

ACE2 of the heart: From angiotensin I to angiotensin (1–7)

Therapeutic Targets in Liver Transplantation: Angiotensin II in Nonsteatotic Grafts and Angiotensin-(1—7) in Steatotic Grafts

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