ACE phenotyping in human heart
that will be used for the development of blood based assay for identification of patients with the increased level of heart ACE (i.e. with the increased risk of atrial fibrillation).
Background. 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 endothelial cells in the heart and lung.
Methods/Principal findings. 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 human heart tissues was 10-15 lower than that in lung. “Conformational fingerprint” of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on ACE) significantly differed from that of lung ACE which reflects differences in the local conformations of these ACEs, likely due to different ACE glycosylation in the heart and lung tissues. Substrate specificity of the heart and lung ACEs towards a number of synthetic substrates also differed. Moreover, apparent ACE activity as well as local conformation of ACE in the atria slightly differed from those in ventricles. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in the heart and lung tissues.
Conclusions. Conclusions. The significant differences in the local conformations of heart ACE (originated from heart endothelial cells and likely myofibroblasts) and lung ACE (originated from lung endothelial cells) allow us to suggest that the properties and functions of ACE could be sensitive to the microenvironment and be regulated by constituents of tissues and blood, this regulation could depend on a set of possible ACE effectors in heart and lung tissues.
Therefore, significant structural differences in ACE from heart and ACE from lung demonstrated in this study may be the base for the generation of mAbs, which will distinguish these two ACEs. Such mAbs may be used for the development of blood based assay for quantification of heart-derived ACE in the blood for identification of the patients with the increased level of heart ACE (i.e. with the increased risk of atrial fibrillation).