Phenotyping Angiotensin-Converting Enzyme in Blood: A Necessary Approach for Precision Medicine
| Autor: | Olga V. Kurilova, A A Kamalov, L M Samokhodskaya, Mark Jain, Sergei M. Danilov, Steven M. Dudek, Alexander P Bobkov |
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| Rok vydání: | 2020 |
| Předmět: |
Angiotensins
medicine.drug_class Angiotensin-Converting Enzyme Inhibitors 030204 cardiovascular system & hematology Pharmacology Peptidyl-Dipeptidase A Monoclonal antibody 03 medical and health sciences 0302 clinical medicine Medicine Humans Clinical significance Precision Medicine chemistry.chemical_classification biology business.industry Angiotensin-converting enzyme General Medicine ACE secretase Precision medicine Phenotype Blood pressure Enzyme chemistry biology.protein business Peptides 030217 neurology & neurosurgery |
| Zdroj: | The journal of applied laboratory medicine. 6(5) |
| ISSN: | 2576-9456 |
| Popis: | Background Angiotensin-converting enzyme (ACE) metabolizes a number of important peptides participating in blood pressure regulation and vascular remodeling. Elevated ACE expression in tissues (which is generally reflected by ACE in blood) is associated with increased risk of cardiovascular diseases. Elevated ACE in blood is also a marker for granulomatous diseases. Methods We applied our novel approach—ACE phenotyping—to characterize serum ACE in 300 unrelated patients and to establish normal values for ACE levels. ACE phenotyping includes (a) determination of ACE activity with 2 substrates (Z-Phe-His-Leu [ZPHL] and Hip-His-Leu [HHL]), (b) calculation of a ratio for hydrolysis of ZPHL and HHL, and (c) quantification of ACE immunoreactive protein levels and ACE conformation with a set of monoclonal antibodies (mAbs) to ACE. Results Only a combination of ACE activity determination with 2 substrates and quantification of the amount of ACE immunoreactive protein with mAbs 1G12 and 9B9 allows for the unequivocal detection of the presence of ACE inhibitors in the blood. After excluding such subjects, we were able to establish normal values of ACE in healthy populations: 50%–150% from control pooled serum. This ACE phenotyping approach in screening format with special attention to outliers can also identify patients with various mutations in ACE and may help to identify the as yet unknown ACE secretase or other mechanistic details of precise regulation of ACE expression. Conclusions ACE phenotyping is a promising new approach with potential clinical significance to advance precision medicine screening techniques by establishing different risk groups based on ACE phenotype. |
| Databáze: | OpenAIRE |
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