{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T08:53:45Z","timestamp":1778662425788,"version":"3.51.4"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","funder":[{"DOI":"10.13039\/100000963","name":"American Diabetes Association Research Foundation","doi-asserted-by":"publisher","award":["1-19-JDF-035"],"award-info":[{"award-number":["1-19-JDF-035"]}],"id":[{"id":"10.13039\/100000963","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pittsburgh Center for Kidney Research","award":["P30 DK079307"],"award-info":[{"award-number":["P30 DK079307"]}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01 HL136267"],"award-info":[{"award-number":["P01 HL136267"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["16GRNT31050004"],"award-info":[{"award-number":["16GRNT31050004"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["RO3AGO52848"],"award-info":[{"award-number":["RO3AGO52848"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["RO1HL141540"],"award-info":[{"award-number":["RO1HL141540"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2021,6,25]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale:<\/jats:title>\n                    <jats:p>Cleavage of the extracellular domain of the PRR ([pro]renin receptor) yields a soluble fragment (sPRR). Although changes in plasma sPRR levels have been reported in hypertension, the causal role of sPRR in blood pressure regulation is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Determine the role of sPRR in blood pressure regulation at baseline and following Ang II (angiotensin II)\u2013induced hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>\n                      CRISPR-Cas9 was used to mutate the cleavage site of the PRR such that sPRR is not generated. Because the gene encoding PRR is on the X-chromosome and male mutant sPRR mice are infertile, only male mice were studied. Mutant sPRR mice had virtually undetectable plasma sPRR levels compared with littermate controls. Mutant sPRR mice had normal survival and development and no apparent histological abnormalities in the kidney, heart, or aorta despite lower body weight. During normal Na\n                      <jats:sup>+<\/jats:sup>\n                      intake, no differences in food or water intake, urinary water or Na\n                      <jats:sup>+<\/jats:sup>\n                      excretion, or acid-base status were observed between control and mutant sPRR mice. Compared with controls, mutant sPRR mice had lower blood pressure at baseline and an attenuated hypertensive response to 2 weeks of Ang II infusion (400 ng\/kg per minute) which was partially reversed by infusion of mouse recombinant sPRR. Mutant sPRR mice also had lower albuminuria, renal tubular injury, and oxidative stress relative to control mice post-Ang II infusion. Furthermore, mesenteric arteries from mutant sPRR mice displayed reduced Ang II\u2013induced vasocontraction and greater acetylcholine, but not sodium nitroprusside, evoked vasorelaxation under baseline conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Loss of sPRR reduces blood pressure at baseline and decreases Ang II\u2013induced hypertension and renal injury. These effects of sPRR loss are associated with greater endothelium-dependent but not independent vasorelaxation of resistance-sized arteries.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.120.317532","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T10:08:07Z","timestamp":1619172487000},"page":"50-62","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Loss of Soluble (Pro)renin Receptor Attenuates Angiotensin-II Induced Hypertension and Renal Injury"],"prefix":"10.1161","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5312-1100","authenticated-orcid":true,"given":"Nirupama","family":"Ramkumar","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension (N.R., D.S., C.S.P., C.H., W.W., D.E.K.), University of Utah Health, Salt Lake City."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Stuart","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension (N.R., D.S., C.S.P., C.H., W.W., D.E.K.), University of Utah Health, Salt Lake City."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin S.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension (N.R., D.S., C.S.P., C.H., W.W., D.E.K.), University of Utah Health, Salt Lake City."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension (N.R., D.S., C.S.P., C.H., W.W., D.E.K.), University of Utah Health, Salt Lake City."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Wheatley","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension (N.R., D.S., C.S.P., C.H., W.W., D.E.K.), University of Utah Health, Salt Lake City."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae","family":"Min Cho","sequence":"additional","affiliation":[{"name":"Nutrition and Integrative Physiology (J.M.C., J.D.S.), University of Utah Health, Salt Lake City."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J David","family":"Symons","sequence":"additional","affiliation":[{"name":"Nutrition and Integrative Physiology (J.M.C., J.D.S.), University of Utah Health, Salt Lake City."},{"name":"Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City (J.D.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald E.","family":"Kohan","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension (N.R., D.S., C.S.P., C.H., W.W., D.E.K.), University of Utah Health, Salt Lake 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