{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:26:44Z","timestamp":1762918004010,"version":"build-2065373602"},"reference-count":81,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T00:00:00Z","timestamp":1565308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS089707","HL115036"],"award-info":[{"award-number":["NS089707","HL115036"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heart failure (HF) patients frequently have elevated plasma renin activity. We examined the significance of elevated plasma renin activity in a translationally-relevant model of dilated cardiomyopathy (DCM), which replicates the progressive stages (A\u2013D) of human HF. Female mice with DCM and elevated plasma renin activity concentrations were treated with a direct renin inhibitor (aliskiren) in a randomized, blinded fashion beginning at Stage B HF. By comparison to controls, aliskiren treatment normalized pathologically elevated plasma renin activity (p &lt; 0.001) and neprilysin levels (p &lt; 0.001), but did not significantly alter pathological changes in plasma aldosterone, angiotensin II, atrial natriuretic peptide, or corin levels. Aliskiren improved cardiac systolic function (ejection fraction, p &lt; 0.05; cardiac output, p &lt; 0.01) and significantly reduced the longitudinal development of edema (extracellular water, p &lt; 0.0001), retarding the transition from Stage B to Stage C HF. The normalization of elevated plasma renin activity reduced the loss of body fat and lean mass (cachexia\/sarcopenia), p &lt; 0.001) and prolonged survival (p &lt; 0.05). In summary, the normalization of plasma renin activity retards the progression of experimental HF by improving cardiac systolic function, reducing the development of systemic edema, cachexia\/sarcopenia, and mortality. These data suggest that targeting pathologically elevated plasma renin activity may be beneficial in appropriately selected HF patients.<\/jats:p>","DOI":"10.3390\/ijms20163886","type":"journal-article","created":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T11:11:31Z","timestamp":1565349091000},"page":"3886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Normalizing Plasma Renin Activity in Experimental Dilated Cardiomyopathy: Effects on Edema, Cachexia, and Survival"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7633-2210","authenticated-orcid":false,"given":"Ryan D.","family":"Sullivan","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine\u2013Phoenix, Phoenix, AZ 85004, USA"},{"name":"Department of Comparative Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radhika M.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine\u2013Phoenix, Phoenix, AZ 85004, USA"},{"name":"Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranjana","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine\u2013Phoenix, Phoenix, AZ 85004, USA"},{"name":"Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-9029","authenticated-orcid":false,"given":"Inna P.","family":"Gladysheva","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine\u2013Phoenix, Phoenix, AZ 85004, USA"},{"name":"Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy L.","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine\u2013Phoenix, Phoenix, AZ 85004, USA"},{"name":"Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1056\/NEJM199908193410806","article-title":"Hormones and hemodynamics in heart failure","volume":"341","author":"Schrier","year":"1999","journal-title":"N. 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