Aug 5, 2017

ACE phenotyping in human heart

PloS One
Victoria E TikhomirovaSergei M Danilov

Abstract

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. 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,...Continue Reading

  • References39
  • Citations3

References

  • References39
  • Citations3

Mentioned in this Paper

Monoclonal Antibodies
N-(2-acetamido)-2-aminoethanesulfonic acid
Lung
Blood Pressure Regulation
Blood Vessel
Tissue Specificity
ACE2
ACE protein, human
Right Atrial Structure
Organ

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