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ACE phenotyping in human heart.

Victoria E Tikhomirova1,2, Olga A Kost1,2, Olga V Kryukova1,2

  • 1Chemical Faculty, M.V. Lomonosov Moscow State University, Moscow, Russia.

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|August 4, 2017
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Summary

Heart and lung angiotensin-converting enzyme (ACE) exhibit distinct conformations and properties, indicating tissue specificity. This finding supports developing diagnostic tools for conditions like atrial fibrillation.

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Area of Science:

  • Biochemistry
  • Cardiovascular Biology

Background:

  • Angiotensin-converting enzyme (ACE) is a key enzyme in blood pressure regulation and vascular remodeling.
  • ACE is expressed on endothelial cells, including those in the heart, as a type-1 membrane glycoprotein.

Purpose of the Study:

  • To investigate potential differences in the conformation and properties of cardiac ACE compared to pulmonary ACE.
  • To explore the tissue-specific characteristics of ACE in the human heart and lungs.

Main Methods:

  • ACE phenotyping was conducted on human heart and lung tissues, assessing ACE levels, conformation, and kinetics.
  • Conformational analysis involved mapping the binding patterns of 17 monoclonal antibodies (mAbs) to ACE epitopes.
  • Comparisons included ACE activity, substrate specificity, and pH optima between heart and lung ACE.

Main Results:

  • ACE activity was 10-15 times lower in heart tissues than in lung tissues.
  • The "conformational fingerprint" of heart ACE significantly differed from lung ACE, suggesting distinct local conformations.
  • Differences in substrate specificity and pH optima were observed between cardiac and pulmonary ACE.
  • Intra-cardiac variations in ACE activity, conformation, and inhibitor content were noted between atria and ventricles.

Conclusions:

  • Significant differences in conformation and kinetics highlight the tissue specificity of ACE.
  • These findings provide a structural basis for developing mAbs that can differentiate between heart and lung ACE.
  • Such antibodies could form the foundation for a blood test to predict atrial fibrillation risk.