{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:24:09Z","timestamp":1787009049418,"version":"build-2736575974"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100008523","name":"University of Illinois at Chicago Center for Clinical and Translational Science","doi-asserted-by":"crossref","award":["UL1TR002003"],"award-info":[{"award-number":["UL1TR002003"]}],"id":[{"id":"10.13039\/100008523","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We applied our novel approach\u2014ACE phenotyping\u2014to 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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%\u2013150% 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jalm\/jfab032","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T18:23:44Z","timestamp":1617906224000},"page":"1179-1191","source":"Crossref","is-referenced-by-count":15,"title":["Phenotyping Angiotensin-Converting Enzyme in Blood: A Necessary Approach for Precision Medicine"],"prefix":"10.1093","volume":"6","author":[{"given":"Larisa M","family":"Samokhodskaya","sequence":"first","affiliation":[{"name":"Medical Center, Moscow University, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"Jain","sequence":"additional","affiliation":[{"name":"Medical Center, Moscow University, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V","family":"Kurilova","sequence":"additional","affiliation":[{"name":"Medical Center, Moscow University, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander P","family":"Bobkov","sequence":"additional","affiliation":[{"name":"Faculty of Fundamental Medicine, Moscow University, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armais A","family":"Kamalov","sequence":"additional","affiliation":[{"name":"Medical Center, Moscow University, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M","family":"Dudek","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy,Department of Medicine, University of Illinois at Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei M","family":"Danilov","sequence":"additional","affiliation":[{"name":"Medical Center, Moscow University, Moscow, Russia"},{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy,Department of Medicine, University of Illinois at Chicago, IL, USA"},{"name":"Department of Medicine, University of Arizona Health Sciences, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"2021090112220669700_jfab032-B1","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/B978-0-12-382219-2.00098-3","volume-title":"Handbook of proteolytic enzymes","author":"Sturrock","year":"2013"},{"key":"2021090112220669700_jfab032-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/pr.112.006809","article-title":"A modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme","volume":"65","author":"Bernstein","year":"2012","journal-title":"Pharmacol Rev"},{"key":"2021090112220669700_jfab032-B3","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1161\/01.ATV.3.6.581","article-title":"Angiotensin-converting enzyme in cultured endothelial cells. 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