General Information:

Id: 11,776 (click here to show other Interactions for entry)
Diseases: Cardiovascular disease
Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mammalia
review
Reference: Bader M(2013) ACE2, angiotensin-(1-7), and Mas: the other side of the coin Pflugers Arch. 465: 79-85 [PMID: 23463883]

Interaction Information:

Comment Angiotensin-(1–7) [Ang-(1–7)] was discovered 1988 as a product of angiotensin I (Ang I) degradation by enzymes from the brainstem. Angiotensin-converting enzyme (ACE), which classically generates Ang II from Ang I, was shown to degrade Ang-(1–7) into inactive peptides, in particular Ang-(1–5).
Formal Description
Interaction-ID: 116574

gene/protein

ACE

decreases_quantity of

gene/protein

Angiotensin (1-7)

Drugbank entries Show/Hide entries for ACE
Comment Angiotensin peptides are metabolized by several subsequent enzymatic steps: First, renin cleaves angiotensinogen, into angiotensin I (Ang I). Ang I can be metabolized by angiotensin-converting enzyme (ACE) resulting in the production of the bioactive octapeptide angiotensin II (Ang II), which interacts with AT1 and AT2 receptors. Alternatively, it can be processed first by ACE2 to the inactive peptide Ang-(1–9) and then by ACE to Ang-(1–7) or by neutral endopeptidase 24.11 (NEP) or prolylendopeptidase (PEP) directly to Ang-(1–7). Ang-(1–7) can also be generated by ACE2 from Ang II and interacts with its receptor Mas.
Formal Description
Interaction-ID: 116583

gene/protein

ACE

increases_quantity of

gene/protein

Angiotensin (1-7)

Drugbank entries Show/Hide entries for ACE
Comment Angiotensin peptides are metabolized by several subsequent enzymatic steps: First, renin cleaves angiotensinogen, into angiotensin I (Ang I). Ang I can be metabolized by angiotensin-converting enzyme (ACE) resulting in the production of the bioactive octapeptide angiotensin II (Ang II), which interacts with AT1 and AT2 receptors. Alternatively, it can be processed first by ACE2 to the inactive peptide Ang-(1–9) and then by ACE to Ang-(1–7) or by neutral endopeptidase 24.11 (NEP) or prolylendopeptidase (PEP) directly to Ang-(1–7). Ang-(1–7) can also be generated by ACE2 from Ang II and interacts with its receptor Mas.
Formal Description
Interaction-ID: 116585

gene/protein

MME

increases_quantity of

gene/protein

Angiotensin (1-7)

Drugbank entries Show/Hide entries for MME
Comment Angiotensin peptides are metabolized by several subsequent enzymatic steps: First, renin cleaves angiotensinogen, into angiotensin I (Ang I). Ang I can be metabolized by angiotensin-converting enzyme (ACE) resulting in the production of the bioactive octapeptide angiotensin II (Ang II), which interacts with AT1 and AT2 receptors. Alternatively, it can be processed first by ACE2 to the inactive peptide Ang-(1–9) and then by ACE to Ang-(1–7) or by neutral endopeptidase 24.11 (NEP) or prolylendopeptidase (PEP) directly to Ang-(1–7). Ang-(1–7) can also be generated by ACE2 from Ang II and interacts with its receptor Mas.
Formal Description
Interaction-ID: 116587

gene/protein

PREP

increases_quantity of

gene/protein

Angiotensin (1-7)

Drugbank entries Show/Hide entries for PREP
Comment Angiotensin peptides are metabolized by several subsequent enzymatic steps: First, renin cleaves angiotensinogen, into angiotensin I (Ang I). Ang I can be metabolized by angiotensin-converting enzyme (ACE) resulting in the production of the bioactive octapeptide angiotensin II (Ang II), which interacts with AT1 and AT2 receptors. Alternatively, it can be processed first by ACE2 to the inactive peptide Ang-(1–9) and then by ACE to Ang-(1–7) or by neutral endopeptidase 24.11 (NEP) or prolylendopeptidase (PEP) directly to Ang-(1–7). Ang-(1–7) can also be generated by ACE2 from Ang II and interacts with its receptor Mas.
Formal Description
Interaction-ID: 116589

gene/protein

ACE2

increases_quantity of

gene/protein

Angiotensin (1-7)

Drugbank entries Show/Hide entries for ACE2
Comment Prolylcarboxypeptidase (PRCP) removes the C-terminal phenylalanine from AngII, liberating the heptapeptide Ang-(1–7).
Formal Description
Interaction-ID: 116591

gene/protein

PRCP

increases_quantity of

gene/protein

Angiotensin (1-7)

Comment Angiotensin peptides are metabolized by several subsequent enzymatic steps: First, renin cleaves angiotensinogen, into angiotensin I (Ang I). Ang I can be metabolized by angiotensin-converting enzyme (ACE) resulting in the production of the bioactive octapeptide angiotensin II (Ang II), which interacts with AT1 and AT2 receptors. Alternatively, it can be processed first by ACE2 to the inactive peptide Ang-(1–9) and then by ACE to Ang-(1–7) or by neutral endopeptidase 24.11 (NEP) or prolylendopeptidase (PEP) directly to Ang-(1–7). Ang-(1–7) can also be generated by ACE2 from Ang II and interacts with its receptor Mas.
Formal Description
Interaction-ID: 116592

gene/protein

Angiotensin (1-7)

increases_activity of

gene/protein

MAS1

Comment Ang-(1–7) has been reported to be vasodilatory, antithrombotic, and antiproliferative. Most of these actions are mediated by changes in the redox balance in the vascular wall initiated by Ang-(1–7) via Mas.
Formal Description
Interaction-ID: 116598

gene/protein

Angiotensin (1-7)

increases_activity of

process

vasodilation

Comment Ang-(1–7) has been reported to be vasodilatory, antithrombotic, and antiproliferative. Most of these actions are mediated by changes in the redox balance in the vascular wall initiated by Ang-(1–7) via Mas.
Formal Description
Interaction-ID: 116600

gene/protein

Angiotensin (1-7)

decreases_activity of

phenotype

thrombosis

Comment Ang-(1–7) has been reported to be vasodilatory, antithrombotic, and antiproliferative. Most of these actions are mediated by changes in the redox balance in the vascular wall initiated by Ang-(1–7) via Mas.
Formal Description
Interaction-ID: 116601

gene/protein

Angiotensin (1-7)

decreases_activity of

Comment Ang-(1–7) triggers NO release by Akt phosphorylation inducing the activation of endothelial NO synthase and inhibits Ang II-induced reactive oxygen species (ROS) production in endothelial cells. Accordingly, vessels of Mas-deficient mice produce more ROS and less NO leading to an impaired in vivo endothelial function and increased blood pressure. In the opposite, an improved endothelial function was observed in stroke-prone spontaneously hypertensive rats (SHRSP) expressing a human ACE2 transgene in vascular smooth muscle cells.
Formal Description
Interaction-ID: 116602

gene/protein

Angiotensin (1-7)

increases_quantity of

drug/chemical compound

NO

in vascular endothelial cells
Comment Ang-(1–7) triggers NO release by Akt phosphorylation inducing the activation of endothelial NO synthase and inhibits Ang II-induced reactive oxygen species (ROS) production in endothelial cells. Accordingly, vessels of Mas-deficient mice produce more ROS and less NO leading to an impaired in vivo endothelial function and increased blood pressure. In the opposite, an improved endothelial function was observed in stroke-prone spontaneously hypertensive rats (SHRSP) expressing a human ACE2 transgene in vascular smooth muscle cells.
Formal Description
Interaction-ID: 116604

gene/protein

Angiotensin (1-7)

decreases_quantity of

drug/chemical compound

Reactive oxygen species

in vascular endothelial cells
Comment Ang-(1–7) triggers NO release by Akt phosphorylation inducing the activation of endothelial NO synthase and inhibits Ang II-induced reactive oxygen species (ROS) production in endothelial cells. Accordingly, vessels of Mas-deficient mice produce more ROS and less NO leading to an impaired in vivo endothelial function and increased blood pressure. In the opposite, an improved endothelial function was observed in stroke-prone spontaneously hypertensive rats (SHRSP) expressing a human ACE2 transgene in vascular smooth muscle cells.
Formal Description
Interaction-ID: 116605

gene/protein

Angiotensin (1-7)

increases_activity of

gene/protein

NOS3

in vascular endothelial cells
Drugbank entries Show/Hide entries for NOS3
Comment In atherosclerosis, the ACE2/Ang-(1–7)/Mas axis was shown to be protective. The genetic ablation of ACE2 significantly increases, and transgenic vascular ACE2 over-expression decreases plaque formation in atherosclerotic apolipoprotein E or LDL receptor-deficient mice. In one study, the transfer of ACE2-deficient bone marrow into LDL receptor-deficient mice was already sufficient to aggravate plaque formation indicating that the enzyme on leukocytes is particularly beneficial in the atherosclerotic process. Moreover, long-term Ang-(1–7) treatment induces protective effects in such animals. In these cases again, an improvement of the redox balance by Ang-(1–7) has been reported to be pivotal for the anti-atherogenic effect.
Formal Description
Interaction-ID: 116606

gene/protein

Angiotensin (1-7)

decreases_activity of

Comment Ang II-induced kidney damage and diabetic nephropathy are aggravated in ACE2-deficient mice, and the Ang II effects are ameliorated by recombinant ACE2 in wild-type animals. Ang-(1–7) infusion reverts diabetic renal damage in mice and rats, and Mas agonists protect the kidney from ischemia/reperfusion damage. The mechanism involved in most of these cases seems to be a reductionin oxidative stress and reduced fibrosis by the components of the ACE2/Ang-(1–7)/Mas axis.
Formal Description
Interaction-ID: 116610

gene/protein

Angiotensin (1-7)

decreases_activity of

disease

Nephropathy, diabetic

Comment Ang-(1–7) has also been shown to be involved in the normal function of the kidney by influencing sodium reabsorption. The effects of the peptide seem to be biphasic with an antidiuretic action at low concentration and diuretic effects at high levels.
Formal Description
Interaction-ID: 116612

gene/protein

Angiotensin (1-7)

affects_activity of

Comment Besides NO-releasing, antioxidative, NO-increasing, and direct anti-hypertrophic effects on cardiomyocytes, the main actions of Ang-(1–7) in the heart seem to be the regulation of genes involved in fibrosis in cardiac fibroblasts via Mas. Accordingly, Mas agonists attenuate heart failure after myocardial infarction.
Formal Description
Interaction-ID: 116614

gene/protein

Angiotensin (1-7)

affects_activity of

phenotype

cardiac fibrosis

Comment Mas deficiency in mice induces a metabolic syndrome-like state, with dyslipidemia, lower glucose tolerance and insulin sensitivity, hyperinsulinemia, decreased glucose uptake in white adipose cells, and an increase in adipose tissue mass. In accordance, chronically increased Ang-(1–7) levels in transgenic rats reduce the amount of fat tissue and plasma lipid levels and enhance glucose tolerance and insulin sensitivity.
Formal Description
Interaction-ID: 116624

gene/protein

Angiotensin (1-7)

decreases_activity of

Comment Mas deficiency in mice induces a metabolic syndrome-like state, with dyslipidemia, lower glucose tolerance and insulin sensitivity, hyperinsulinemia, decreased glucose uptake in white adipose cells, and an increase in adipose tissue mass. In accordance, chronically increased Ang-(1–7) levels in transgenic rats reduce the amount of fat tissue and plasma lipid levels and enhance glucose tolerance and insulin sensitivity.
Formal Description
Interaction-ID: 116625

gene/protein

Angiotensin (1-7)

decreases_activity of

disease

Insulin resistance