{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:33:59Z","timestamp":1786700039369,"version":"build-2736575974"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["20020190100030BA"],"award-info":[{"award-number":["20020190100030BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"CONICET","doi-asserted-by":"publisher","award":["PIP 11220200101851CO"],"award-info":[{"award-number":["PIP 11220200101851CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"ANPCYT","doi-asserted-by":"publisher","award":["PICT 2019-2384"],"award-info":[{"award-number":["PICT 2019-2384"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>ADAM17 (A disintegrin and metalloproteinase 17) contributes to angiotensin-converting enzyme (ACE) 2 shedding in response to angiotensin II\u2013AT1 receptor signaling, potentially shifting the renin\u2013angiotensin system toward its pressor arm. We investigated whether ACE inhibitor (ACEI) or AT1 receptor blocker (ARB) therapy modulates ADAM17 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>ADAM17 protein expression was evaluated by immunohistochemistry in alveolar type II pneumocytes of lung parenchymal samples from untreated control patients (n\u2009=\u200920) and patients treated with ACEI (n\u2009=\u200921) or ARB (n\u2009=\u200917; total ACEI\/ARB-treated patients\u2009=\u200938).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There were no significant differences in the proportion of ADAM17-expressing type II pneumocytes between patients without hypertension and ACEI\/ARB-treated patients with hypertension (56.1\u2009\u00b1\u20094.3% vs. 45.8\u2009\u00b1\u20093.1%, respectively). Similarly, no differences were observed according to smoking status (50.6\u2009\u00b1\u20094.1% in never smokers, 48.4\u2009\u00b1\u20094.0% in current smokers, and 50.8\u2009\u00b1\u20096.8% in former smokers) or sex (49.7\u2009\u00b1\u20094.2% in women vs. 49.1\u2009\u00b1\u20093.3% in men). In contrast, a significant age-related decline in the proportion of ADAM17-expressing type II pneumocytes was observed (56.2\u2009\u00b1\u20093.5% in patients &amp;lt;60 years vs. 43.0\u2009\u00b1\u20093.5% in patients \u226560 years; P\u2009=\u2009.005).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that ACEI\/ARB therapy, while targeting the pressor axis of the RAS, maintains ADAM17 expression at levels comparable to those in patients without hypertension. ACEI\/ARB therapy may represent a potential strategy for the treatment of ADAM17-mediated cardiovascular, pulmonary, and inflammatory diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajh\/hpag040","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:42:21Z","timestamp":1777030941000},"page":"1061-1066","source":"Crossref","is-referenced-by-count":0,"title":["ADAM17 expression in ACEI\/ARB-treated patients with hypertension was comparable to that observed in patients without hypertension"],"prefix":"10.1093","volume":"39","author":[{"given":"Nora L","family":"Falcoff","sequence":"first","affiliation":[{"name":"Servicio Unificado de Patolog\u00eda, Hospital Prov de T\u00f3rax \u201cDr. A. Cetr\u00e1ngolo\u201d y Municipal de Vicente L\u00f3pez \u201cProf. B. Houssay\u201d , Buenos Aires,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela R","family":"Guman","sequence":"additional","affiliation":[{"name":"Servicio Unificado de Patolog\u00eda, Hospital Prov de T\u00f3rax \u201cDr. A. Cetr\u00e1ngolo\u201d y Municipal de Vicente L\u00f3pez \u201cProf. B. Houssay\u201d , Buenos Aires,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando F","family":"Seguel","sequence":"additional","affiliation":[{"name":"Servicio de Neumonolog\u00eda, Hospital Prov de T\u00f3rax \u201cDr. A. Cetr\u00e1ngolo\u201d , Buenos Aires,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4282-4011","authenticated-orcid":false,"given":"Gabriela C","family":"Tabaj","sequence":"additional","affiliation":[{"name":"Servicio de Neumonolog\u00eda, Hospital Prov de T\u00f3rax \u201cDr. A. Cetr\u00e1ngolo\u201d , Buenos Aires,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Honickman","sequence":"additional","affiliation":[{"name":"Servicio de Neumonolog\u00eda, Hospital Prov de T\u00f3rax \u201cDr. A. Cetr\u00e1ngolo\u201d , Buenos Aires,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucila","family":"Daroca","sequence":"additional","affiliation":[{"name":"Servicio de Neumonolog\u00eda, Hospital Prov de T\u00f3rax \u201cDr. A. Cetr\u00e1ngolo\u201d , Buenos Aires,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9405-4733","authenticated-orcid":false,"given":"Myriam","family":"Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Matem\u00e1tica, Buenos Aires ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7103-5505","authenticated-orcid":false,"given":"Martin","family":"Salazar","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata, Hospital Interzonal General Agudos San Mart\u00edn de La Plata , La Plata,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9402-7439","authenticated-orcid":false,"given":"Gianfranco","family":"Parati","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milan,","place":["Italy"]},{"name":"Department of Cardiology, San Luca Hosiptal, IRCCS, Istituto Auxologico Italiano , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-0388","authenticated-orcid":false,"given":"Mariela M","family":"Gironacci","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Matem\u00e1tica, Buenos Aires ,","place":["Argentina"]},{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Dpto. Qu\u00edmica Biol\u00f3gica, IQUIFIB (UBA-CONICET), Buenos Aires,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"2026081404475671700_hpag040-B1","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1161\/CIRCRESAHA.120.317015","article-title":"Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the Renin-Angiotensin system: celebrating the 20th anniversary of the discovery of ACE2","volume":"126","author":"Gheblawi","year":"2020","journal-title":"Circ Res"},{"key":"2026081404475671700_hpag040-B2","doi-asserted-by":"crossref","first-page":"17441","DOI":"10.3390\/ijms242417441","article-title":"Angiotensin-converting enzyme 2 (ACE2) signaling in pulmonary arterial hypertension: underpinning mechanisms and potential targeting strategies","volume":"24","author":"Papavassiliou","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026081404475671700_hpag040-B3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/febs.16923","article-title":"The protease ADAM17 at the crossroads of disease: revisiting its significance in inflammation, cancer, and beyond","volume":"291","author":"Saad","year":"2024","journal-title":"Febs J"},{"key":"2026081404475671700_hpag040-B4","doi-asserted-by":"crossref","first-page":"1640090","DOI":"10.3389\/fphar.2025.1640090","article-title":"ADAM17 as a promising therapeutic target: from structural basis to inhibitor discovery in human diseases","volume":"16","author":"Liu","year":"2025","journal-title":"Front Pharmacol"},{"key":"2026081404475671700_hpag040-B5","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1161\/CIRCRESAHA.113.301811","article-title":"Brain angiotensin-converting enzyme type 2 shedding contributes to the development of neurogenic hypertension","volume":"113","author":"Xia","year":"2013","journal-title":"Circ Res"},{"key":"2026081404475671700_hpag040-B6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1161\/CIRCRESAHA.116.310509","article-title":"Clinical relevance and role of neuronal AT1 receptors in ADAM17-mediated ACE2 shedding in neurogenic hypertension","volume":"121","author":"Xu","year":"2017","journal-title":"Circ Res"},{"key":"2026081404475671700_hpag040-B7","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.healun.2020.07.003","article-title":"Lung ACE2 and ADAM17 in pulmonary arterial hypertension: Implications for COVID-19?","volume":"39","author":"Perez-Vizca\u00edno","year":"2020","journal-title":"J Heart Lung Transplant"},{"key":"2026081404475671700_hpag040-B8","doi-asserted-by":"crossref","first-page":"1702638","DOI":"10.1183\/13993003.02638-2017","article-title":"Potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension","volume":"51","author":"Hemnes","year":"2018","journal-title":"Eur Respir J"},{"key":"2026081404475671700_hpag040-B9","doi-asserted-by":"crossref","first-page":"120324","DOI":"10.1016\/j.lfs.2022.120324","article-title":"Renin-angiotensin system blockade on angiotensin-converting enzyme 2 and TMPRSS2 in human type II pneumocytes","volume":"293","author":"Silva","year":"2022","journal-title":"Life Sci"},{"key":"2026081404475671700_hpag040-B10","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00428-009-0748-4","article-title":"Expression of ADAMs (\u201ca disintegrin and metalloprotease\u201d) in the human lung","volume":"454","author":"Dijkstra","year":"2009","journal-title":"Virchows Arch"},{"key":"2026081404475671700_hpag040-B11","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/jb\/mvz113","article-title":"Decreased ADAM17 expression in the lungs of \u03b1-klotho reduced mouse","volume":"167","author":"Akasaka-Manya","year":"2020","journal-title":"J Biochem"},{"key":"2026081404475671700_hpag040-B12","doi-asserted-by":"crossref","first-page":"26052","DOI":"10.1038\/srep26052","article-title":"Finding novel distinctions between the sAPP\u03b1-mediated anabolic biochemical pathways in autism spectrum disorder and fragile X syndrome plasma and brain tissue","volume":"6","author":"Ray","year":"2016","journal-title":"Sci Rep"},{"key":"2026081404475671700_hpag040-B13","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1161\/HYPERTENSIONAHA.116.07620","article-title":"Vascular ADAM17 as a novel therapeutic target in mediating cardiovascular hypertrophy and perivascular fibrosis induced by angiotensin II","volume":"68","author":"Takayanagi","year":"2016","journal-title":"Hypertension"},{"key":"2026081404475671700_hpag040-B14","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12964-023-01087-3","article-title":"P38 MAPK activated ADAM17 mediates ACE2 shedding and promotes cardiac remodeling and heart failure after myocardial infarction","volume":"21","author":"Chen","year":"2023","journal-title":"Cell Commun Signal"},{"key":"2026081404475671700_hpag040-B15","doi-asserted-by":"crossref","first-page":"997916","DOI":"10.3389\/fphar.2022.997916","article-title":"ADAM17 knockdown mitigates while ADAM17 overexpression aggravates cardiac fibrosis and dysfunction via regulating ACE2 shedding and myofibroblast transformation","volume":"13","author":"Cheng","year":"2022","journal-title":"Front Pharmacol"},{"key":"2026081404475671700_hpag040-B16","doi-asserted-by":"crossref","first-page":"9497716","DOI":"10.1155\/2023\/9497716","article-title":"miR-145 alleviates smooth muscle cell phenotype transition via ADAM17-mediated ACE2 shedding","volume":"2023","author":"Wen","year":"2023","journal-title":"Int J Hypertens"},{"key":"2026081404475671700_hpag040-B17","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1161\/CIRCRESAHA.118.313181","article-title":"Cell-specific functions of ADAM17 regulate the progression of thoracic aortic aneurysm","volume":"123","author":"Shen","year":"2018","journal-title":"Circ Res"},{"key":"2026081404475671700_hpag040-B18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s40119-019-00150-w","article-title":"A review of the role of bradykinin and nitric oxide in the cardioprotective action of angiotensin-converting enzyme inhibitors: focus on perindopril","volume":"8","author":"Ancion","year":"2019","journal-title":"Cardiol Ther"},{"key":"2026081404475671700_hpag040-B19","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00018-023-04783-y","article-title":"A structural model of the iRhom\u2013ADAM17 sheddase complex reveals functional insights into its trafficking and activity","volume":"80","author":"Kahveci-T\u00fcrk\u00f6z","year":"2023","journal-title":"Cell Mol Life Sci"},{"key":"2026081404475671700_hpag040-B20","doi-asserted-by":"crossref","first-page":"e35012","DOI":"10.7554\/eLife.35012","article-title":"FRMD8 promotes inflammatory and growth factor signalling by stabilising the iRhom\/ADAM17 sheddase complex","volume":"7","author":"K\u00fcnzel","year":"2018","journal-title":"Elife"},{"key":"2026081404475671700_hpag040-B21","doi-asserted-by":"crossref","first-page":"e22234","DOI":"10.1096\/fj.202101521R","article-title":"The collectrin-like part of the SARS-CoV-1 and -2 receptor ACE2 is shed by the metalloproteinases ADAM10 and ADAM17","volume":"36","author":"Niehues","year":"2022","journal-title":"Faseb J"}],"container-title":["American Journal of Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajh\/advance-article-pdf\/doi\/10.1093\/ajh\/hpag040\/68171995\/hpag040.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajh\/article-pdf\/39\/9\/1061\/68171995\/hpag040.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajh\/article-pdf\/39\/9\/1061\/68171995\/hpag040.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:56:12Z","timestamp":1786697772000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajh\/article\/39\/9\/1061\/8663668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":21,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,4,27]]},"published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ajh\/hpag040","relation":{},"ISSN":["0895-7061","1941-7225"],"issn-type":[{"value":"0895-7061","type":"print"},{"value":"1941-7225","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,4,27]]}}}