ACE phenotyping in human heart

Victoria E. Tikhomirova, Olga A. Kost, Olga V. Kryukova, Elena Z. Golukhova, Naida I. Bulaeva, Aigerim Z. Zholbaeva, Leo A. Bokeria, Joe G.N. Garcia, Sergei M. Danilov

Research output: Research - peer-reviewArticle

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.

LanguageEnglish (US)
Article numbere0181976
JournalPLoS ONE
Volume12
Issue number8
DOIs
StatePublished - Aug 1 2017

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peptidyl-dipeptidase A
heart
phenotype
Peptidyl-Dipeptidase A
lungs
Lung
Conformations
tissues
Tissue
enzyme activity
kinetics
angiotensin-converting enzyme inhibitors
Angiotensin-Converting Enzyme Inhibitors
Kinetics
membrane glycoproteins
hematologic tests
glycosylation
substrate specificity
blood vessels
epitopes

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Tikhomirova, V. E., Kost, O. A., Kryukova, O. V., Golukhova, E. Z., Bulaeva, N. I., Zholbaeva, A. Z., ... Danilov, S. M. (2017). ACE phenotyping in human heart. PLoS ONE, 12(8), [e0181976]. DOI: 10.1371/journal.pone.0181976

ACE phenotyping in human heart. / 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.

In: PLoS ONE, Vol. 12, No. 8, e0181976, 01.08.2017.

Research output: Research - peer-reviewArticle

Tikhomirova, VE, Kost, OA, Kryukova, OV, Golukhova, EZ, Bulaeva, NI, Zholbaeva, AZ, Bokeria, LA, Garcia, JGN & Danilov, SM 2017, 'ACE phenotyping in human heart' PLoS ONE, vol 12, no. 8, e0181976. DOI: 10.1371/journal.pone.0181976
Tikhomirova VE, Kost OA, Kryukova OV, Golukhova EZ, Bulaeva NI, Zholbaeva AZ et al. ACE phenotyping in human heart. PLoS ONE. 2017 Aug 1;12(8). e0181976. Available from, DOI: 10.1371/journal.pone.0181976
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./ ACE phenotyping in human heart. In: PLoS ONE. 2017 ; Vol. 12, No. 8.
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