Persistent Link:
http://hdl.handle.net/10150/625490
Title:
ACE phenotyping in human heart
Author:
Tikhomirova, Victoria E.; Kost, Olga A.; Kryukova, Olga V.; Golukhova, Elena Z.; Bulaeva, Naida I.; Zholbaeva, Aigerim Z.; Bokeria, Leo A.; Garcia, Joe G. N.; Danilov, Sergei M. ( 0000-0002-6901-4545 )
Affiliation:
Univ Arizona Hlth Sci
Issue Date:
2017-08-03
Publisher:
PUBLIC LIBRARY SCIENCE
Citation:
ACE phenotyping in human heart 2017, 12 (8):e0181976 PLOS ONE
Journal:
PLOS ONE
Rights:
© 2017 Tikhomirova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.
Collection Information:
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
Abstract:
Aims Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. Methods and results We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10-15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. "Conformational fingerprint" of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Conclusions Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk.
Note:
Open access journal.
ISSN:
1932-6203
PubMed ID:
28771512
DOI:
10.1371/journal.pone.0181976
Version:
Final published version
Sponsors:
Ministry of Science and Education of Russian Federation [14.Z50.31.0026]
Additional Links:
http://dx.plos.org/10.1371/journal.pone.0181976

Full metadata record

DC FieldValue Language
dc.contributor.authorTikhomirova, Victoria E.en
dc.contributor.authorKost, Olga A.en
dc.contributor.authorKryukova, Olga V.en
dc.contributor.authorGolukhova, Elena Z.en
dc.contributor.authorBulaeva, Naida I.en
dc.contributor.authorZholbaeva, Aigerim Z.en
dc.contributor.authorBokeria, Leo A.en
dc.contributor.authorGarcia, Joe G. N.en
dc.contributor.authorDanilov, Sergei M.en
dc.date.accessioned2017-09-13T23:46:04Z-
dc.date.available2017-09-13T23:46:04Z-
dc.date.issued2017-08-03-
dc.identifier.citationACE phenotyping in human heart 2017, 12 (8):e0181976 PLOS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid28771512-
dc.identifier.doi10.1371/journal.pone.0181976-
dc.identifier.urihttp://hdl.handle.net/10150/625490-
dc.description.abstractAims Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. Methods and results We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10-15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. "Conformational fingerprint" of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Conclusions Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk.en
dc.description.sponsorshipMinistry of Science and Education of Russian Federation [14.Z50.31.0026]en
dc.language.isoenen
dc.publisherPUBLIC LIBRARY SCIENCEen
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pone.0181976en
dc.rights© 2017 Tikhomirova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.en
dc.titleACE phenotyping in human hearten
dc.typeArticleen
dc.contributor.departmentUniv Arizona Hlth Scien
dc.identifier.journalPLOS ONEen
dc.description.noteOpen access journal.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen

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