{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T06:02:28Z","timestamp":1769320948515,"version":"3.49.0"},"reference-count":99,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation (South Africa)","doi-asserted-by":"publisher","award":["111798"],"award-info":[{"award-number":["111798"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Angiotensin converting enzyme (ACE) exerts strong modulation of myeloid cell function independently of its cardiovascular arm. The success of the ACE-overexpressing murine macrophage model, ACE 10\/10, in treating microbial infections and cancer opens a new avenue into whether ACE overexpression in human macrophages shares these benefits. Additionally, as ACE inhibitors are a widely used antihypertensive medication, their impact on ACE expressing immune cells is of interest and currently understudied. In the present study, we utilized mass spectrometry to characterize and assess global proteomic changes in an ACE-overexpressing human THP-1 cell line. Additionally, proteomic changes and cellular uptake following treatment with an ACE C-domain selective inhibitor, lisinopril\u2013tryptophan, were also assessed. ACE activity was significantly reduced following inhibitor treatment, despite limited uptake within the cell, and both RNA processing and immune pathways were significantly dysregulated with treatment. Also present were upregulated energy and TCA cycle proteins and dysregulated cytokine and interleukin signaling proteins with ACE overexpression. A novel, functionally enriched immune pathway that appeared both with ACE overexpression and inhibitor treatment was neutrophil degranulation. ACE overexpression within human macrophages showed similarities with ACE 10\/10 murine macrophages, paving the way for mechanistic studies aimed at understanding the altered immune function.<\/jats:p>","DOI":"10.3390\/ijms25137055","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T11:19:02Z","timestamp":1719487142000},"page":"7055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proteomic Analysis of Human Macrophages Overexpressing Angiotensin-Converting Enzyme"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8631-6342","authenticated-orcid":false,"given":"Delia","family":"Oosthuizen","sequence":"first","affiliation":[{"name":"Division of Chemical, Systems and Synthetic Biology, Faculty of Health Sciences, Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tariq A.","family":"Ganief","sequence":"additional","affiliation":[{"name":"Division of Chemical, Systems and Synthetic Biology, Faculty of Health Sciences, Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth E.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA"},{"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward D.","family":"Sturrock","sequence":"additional","affiliation":[{"name":"Division of Chemical, Systems and Synthetic Biology, Faculty of Health Sciences, Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1084\/jem.103.3.295","article-title":"The preparation and function of the hypertensin-converting enzyme","volume":"103","author":"Skeggs","year":"1956","journal-title":"J. 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