About: [Pyr(1)]Apelin-13((1–12)) Is a Biologically Active ACE2 Metabolite of the Endogenous Cardiovascular Peptide [Pyr(1)]Apelin-13

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: [Pyr(1)]Apelin-13((1–12)) Is a Biologically Active ACE2 Metabolite of the Endogenous Cardiovascular Peptide [Pyr(1)]Apelin-13 Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	[Pyr(1)]Apelin-13((1–12)) Is a Biologically Active ACE2 Metabolite of the Endogenous Cardiovascular Peptide [Pyr(1)]Apelin-13
Creator	Cheriyan, Joseph Dyson, Alex Singer, Mervyn Yang, Peiran Brame, Aimée Davenport, Anthony Glen, Robert Kuc, Rhoda Maguire, Janet Wilkinson, Ian Takahashi, Kazuhiro Vaudry, Hubert
Source	Medline; PMC
abstract	Aims: Apelin is a predicted substrate for ACE2, a novel therapeutic target. Our aim was to demonstrate the endogenous presence of the putative ACE2 product [Pyr(1)]apelin-13((1–12)) in human cardiovascular tissues and to confirm it retains significant biological activity for the apelin receptor in vitro and in vivo. The minimum active apelin fragment was also investigated. Methods and Results: [Pyr(1)]apelin-13 incubated with recombinant human ACE2 resulted in de novo generation of [Pyr(1)]apelin-13((1–12)) identified by mass spectrometry. Endogenous [Pyr(1)]apelin-13((1–12)) was detected by immunostaining in human heart and lung localized to the endothelium. Expression was undetectable in lung from patients with pulmonary arterial hypertension. In human heart [Pyr(1)]apelin-13((1–12)) (pK(i) = 8.04 ± 0.06) and apelin-13(F13A) (pK(i) = 8.07 ± 0.24) competed with [(125)I]apelin-13 binding with nanomolar affinity, 4-fold lower than for [Pyr(1)]apelin-13 (pK(i) = 8.83 ± 0.06) whereas apelin-17 exhibited highest affinity (pK(i) = 9.63 ± 0.17). The rank order of potency of peptides to inhibit forskolin-stimulated cAMP was apelin-17 (pD(2) = 10.31 ± 0.28) > [Pyr(1)]apelin-13 (pD(2) = 9.67 ± 0.04) ≥ apelin-13(F13A) (pD(2) = 9.54 ± 0.05) > [Pyr(1)]apelin-13((1–12)) (pD(2) = 9.30 ± 0.06). The truncated peptide apelin-13(R10M) retained nanomolar potency (pD(2) = 8.70 ± 0.04) but shorter fragments exhibited low micromolar potency. In a β-arrestin recruitment assay the rank order of potency was apelin-17 (pD(2) = 10.26 ± 0.09) >> [Pyr(1)]apelin-13 (pD(2) = 8.43 ± 0.08) > apelin-13(R10M) (pD(2) = 8.26 ± 0.17) > apelin-13(F13A) (pD(2) = 7.98 ± 0.04) ≥ [Pyr(1)]apelin-13((1–12)) (pD(2) = 7.84 ± 0.06) >> shorter fragments (pD(2) < 6). [Pyr(1)]apelin-13((1–12)) and apelin-13(F13A) contracted human saphenous vein with similar sub-nanomolar potencies and [Pyr(1)]apelin-13((1–12)) was a potent inotrope in paced mouse right ventricle and human atria. [Pyr(1)]apelin-13((1–12)) elicited a dose-dependent decrease in blood pressure in anesthetized rat and dose-dependent increase in forearm blood flow in human volunteers. Conclusions: We provide evidence that ACE2 cleaves [Pyr(1)]apelin-13 to [Pyr(1)]apelin-13((1–12)) and this cleavage product is expressed in human cardiovascular tissues. We have demonstrated biological activity of [Pyr(1)]apelin-13((1–12)) at the human and rodent apelin receptor in vitro and in vivo. Our data show that reported enhanced ACE2 activity in cardiovascular disease should not significantly compromise the beneficial effects of apelin based therapies for example in PAH.
has issue date	2017-02-28(xsd:dateTime)
bibo:doi	10.3389/fnins.2017.00092
bibo:pmid	28293165
has license	cc-by
sha1sum (hex)	671f1c2956296e84da394af512513ea165882eba
schema:url	https://doi.org/10.3389/fnins.2017.00092
resource representing a document's title	[Pyr(1)]Apelin-13((1–12)) Is a Biologically Active ACE2 Metabolite of the Endogenous Cardiovascular Peptide [Pyr(1)]Apelin-13
has PubMed Central identifier	PMC5329011
has PubMed identifier	28293165
schema:publication	Front Neurosci
resource representing a document's body	covid:671f1c2956296e84da394af512513ea165882eba#body_text
is schema:about of	named entity 'ACTIVE' named entity 'effects' named entity 'cleavage product' named entity 'apelin' named entity 'Peptide' named entity 'OUR' named entity 'RODENT' named entity 'EFFECTS' named entity 'DATA' named entity 'REPORTED' named entity 'DEMONSTRATED' named entity 'IN VIVO' named entity 'BIOLOGICAL ACTIVITY' named entity '288' named entity 'CLEAVES' named entity 'EVIDENCE' named entity 'ENHANCED' named entity 'CARDIOVASCULAR' named entity 'PROVIDE' named entity 'BASED' named entity 'CLEAVAGE' named entity 'ACE2' named entity 'ACE2' named entity 'BIOLOGICALLY' named entity 'PEPTIDE' named entity 'EXAMPLE' named entity 'ENDOGENOUS' named entity 'METABOLITE' named entity 'CARDIOVASCULAR' named entity 'ACTIVITY' named entity 'APELIN' named entity 'CARDIOVASCULAR DISEASE' named entity 'EXPRESSED' named entity 'APELIN RECEPTOR' named entity 'TISSUES' named entity 'COMPROMISE' named entity '283' named entity 'PRODUCT' named entity 'IS A' named entity 'HUMAN' named entity 'BENEFICIAL' named entity '282' named entity 'THERAPIES' named entity 'IN VITRO' named entity 'HAVE' named entity 'PAH' named entity '287' named entity 'apelin' named entity 'demonstrated' named entity 'cardiovascular' named entity 'apelin' named entity 'receptor' named entity 'biological activity' named entity 'Metabolite' named entity 'Endogenous' named entity 'Cardiovascular' named entity 'Apelin' named entity 'ACE2' named entity 'cleaves' named entity 'heart failure' named entity 'forskolin' named entity 'apelin' named entity 'angiotensin II' named entity 'inotrope' named entity 'apelin' named entity 'Pyr' named entity 'blood pressure' named entity 'apelin' named entity 'peptidase' named entity 'sterility'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software