{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:42Z","timestamp":1787022102446,"version":"build-2736575974"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/00984-3"],"award-info":[{"award-number":["2014\/00984-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/00984-3"],"award-info":[{"award-number":["2014\/00984-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/04485-4"],"award-info":[{"award-number":["2015\/04485-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/03954-6"],"award-info":[{"award-number":["2017\/03954-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sickle cell disease (SCD) incurs vaso-occlusive episodes and organ damage, including nephropathy. Despite displaying characteristics of vascular dysfunction, SCD patients tend to present relatively lower systemic blood pressure (BP), via an unknown mechanism. We investigated associations between BP and renin-angiotensin-system (RAS) components in SCD and determined whether an inhibitor of angiotensin converting enzyme (ACE; often used to slow SCD glomerulopathy) further modulates BP and RAS components in a murine model of SCD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>BP was compared in human subjects and mice with\/without SCD. Plasma angiotensin II, ACE and renin were measured by immunoassay. BP was reevaluated after treating mice with enalapril (25 mg\/kg, 5x\/week) for 5 weeks; plasma and organs were stored for angiotensin II and ACE activity measurement, and quantitative real-time PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Diastolic BP and systolic BP were significantly lower in patients and mice with SCD, respectively, compared to controls. Reduced BP was associated with increased plasma renin and markers of kidney damage (mice) in SCD, as well as significantly decreased plasma ACE concentrations and ACE enzyme activity. As expected, enalapril administration lowered BP, plasma angiotensin II and organ ACE activity in control mice. In contrast, enalapril did not further reduce BP or organ ACE activity in SCD mice; however, plasma angiotensin II and renin levels were found to be significantly higher in enalapril-treated SCD mice than those of treated control mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Relative hypotension was confirmed in a murine model of SCD, in association with decreased ACE concentrations in both human and murine disease. Given that ACE inhibition has an accepted role in decreasing BP, further studies should investigate mechanisms by which ACE depletion, via both Ang II-dependent and alternative pathways, could contribute to reduce BP in SCD and understand how ACE inhibition confers Ang II-independent benefits on kidney function in SCD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0263424","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T13:44:42Z","timestamp":1643895882000},"page":"e0263424","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Reduced blood pressure in sickle cell disease is associated with decreased angiotensin converting enzyme (ACE) activity and is not modulated by ACE inhibition"],"prefix":"10.1371","volume":"17","author":[{"given":"Pamela L.","family":"Brito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisson F.","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan","family":"Chweih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Favero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica M. F.","family":"Gotardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4543-5169","authenticated-orcid":true,"given":"Juliete A. F.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia C.","family":"Leonardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla F.","family":"Franco-Penteado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana G.","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson A.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna C.","family":"Zaidan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanase","family":"Billis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Baldanzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise A.","family":"Mashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edson","family":"Antunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara T. Olalla","family":"Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando F.","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5726-7919","authenticated-orcid":true,"given":"Nicola","family":"Conran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"pone.0263424.ref001","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-3-319-06713-1_3","volume-title":"Sickle cell anemia: From basic science to clinical practice.","author":"MH Steinberg","year":"2016"},{"key":"pone.0263424.ref002","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/iub.584","article-title":"Role of oxidative stress in the pathogenesis of sickle cell disease","volume":"64","author":"EN Chirico","year":"2012","journal-title":"IUBMB Life"},{"key":"pone.0263424.ref003","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1182\/blood.V92.7.2551","article-title":"Plasma endothelin-1, cytokine, and prostaglandin E2 levels in sickle cell disease and acute vaso-occlusive sickle crisis","volume":"92","author":"E Graido-Gonzalez","year":"1998","journal-title":"Blood"},{"key":"pone.0263424.ref004","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/978-3-319-77932-4_9","article-title":"Sex Differences in Regulation of Blood Pressure","volume":"1065","author":"JF Reckelhoff","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"pone.0263424.ref005","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/00062752-200303000-00001","article-title":"An emerging role for nitric oxide in sickle cell disease vascular homeostasis and therapy","volume":"10","author":"CD Reiter","year":"2003","journal-title":"Curr Opin Hematol"},{"key":"pone.0263424.ref006","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/archinte.1982.00340190199036","article-title":"Blood pressure in sickle cell disease","volume":"142","author":"PE de Jong","year":"1982","journal-title":"Arch Intern Med"},{"key":"pone.0263424.ref007","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/S0140-6736(81)90611-5","article-title":"Blood pressure in adults with homozygous sickle cell disease","volume":"2","author":"GA Grell","year":"1981","journal-title":"Lancet"},{"key":"pone.0263424.ref008","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1001\/archinte.1981.00340070071015","article-title":"Arterial blood pressure in adults with sickle cell disease","volume":"141","author":"CS Johnson","year":"1981","journal-title":"Arch Intern Med"},{"key":"pone.0263424.ref009","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0002-9343(96)00407-X","article-title":"Natural history of blood pressure in sickle cell disease: risks for stroke and death associated with relative hypertension in sickle cell anemia","volume":"102","author":"CH Pegelow","year":"1997","journal-title":"Am J Med"},{"key":"pone.0263424.ref010","doi-asserted-by":"crossref","first-page":"E65","DOI":"10.1002\/ajh.23278","article-title":"Decades after the cooperative study: a re-examination of systemic blood pressure in sickle cell disease","volume":"87","author":"PC Desai","year":"2012","journal-title":"Am J Hematol"},{"key":"pone.0263424.ref011","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/ajh\/2.1.2","article-title":"Altered vascular reactivity in sickle hemoglobinopathy. 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