{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:47:35Z","timestamp":1784008055949,"version":"3.55.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":1009,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031829","name":"Ceva Sante Animale","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100031829","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Colorado State University\u00a0- Dr. Kaitlyn Brunk received a stipend from the Veterinary Summer Scholars Program, which receives funding from Boehringer-Ingelheim"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The behavior of the comprehensive circulating renin-angiotensin system (RAS) in dogs with myxomatous mitral valve disease (MMVD) before to the onset of congestive heart failure remains largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis\/Objectives<\/jats:title>\n                    <jats:p>The classical and alternative RAS activity and aldosterone concentrations will be significantly higher in dogs with American College of Veterinary Internal Medicine (ACVIM) stage B2\u2009MMVD compared to normal dogs and dogs with ACVIM stage B1\u2009MMVD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>One-hundred seventeen client-owned dogs (normal\u00a0=\u00a060; B1\u00a0=\u00a031; B2\u00a0=\u00a026).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective observational study. Angiotensin peptides (AP) and aldosterone concentrations were measured using liquid chromatography and mass spectrometry. Angiotensin converting enzymes 1 and 2 (ACE, ACE2) and renin activity surrogates were calculated from AP concentrations. Equilibrium dialysis (ED) and immediate protease inhibition (PI) methods of AP quantification were compared in 14 healthy dogs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Core RAS activity and aldosterone concentrations did not differ among the 3 groups. However, the balance between the alternative and classical RAS differed, with dogs with stage B2\u2009MMVD having significantly higher ACE2 activity surrogate (ACE2surr) when compared to normal dogs (adjusted P\u00a0=\u00a0.02; ratio of medians for ACE2surr [B2:normal], 1.89; 95% confidence interval [CI]: 1.4-2.6). The ED and PI methods of AP quantification were highly correlated (AngI, r\u00a0=\u00a0.9, P\u2009&amp;lt;\u2009.0001; AngII, r\u00a0=\u00a0.8, P\u00a0=\u00a0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Circulating alternative RAS activity, specifically the surrogate measure of ACE2 activity, was increased in dogs with stage B2\u2009MMVD as compared to normal dogs. Equilibrium dialysis results are analogous to immediate protease inhibition in dogs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.16687","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T08:21:58Z","timestamp":1679559718000},"page":"875-886","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The classical and alternative circulating renin-angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2828-3113","authenticated-orcid":false,"given":"Hillary H.","family":"Hammond","sequence":"first","affiliation":[{"name":"Colorado State University College of Veterinary Medicine and Biomedical Sciences Department of Clinical Sciences, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3865-6123","authenticated-orcid":false,"given":"Marisa K.","family":"Ames","sequence":"additional","affiliation":[{"name":"Colorado State University College of Veterinary Medicine and Biomedical Sciences Department of Clinical Sciences, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Domenig","sequence":"additional","affiliation":[{"name":"University of California Clinical and Translational Science Center, Department of Public Health Sciences, Division of Biostatistics, , Sacramento, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7427-2402","authenticated-orcid":false,"given":"Brian A.","family":"Scansen","sequence":"additional","affiliation":[{"name":"Colorado State University College of Veterinary Medicine and Biomedical Sciences Department of Clinical Sciences, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuen Tsang","family":"Yang","sequence":"additional","affiliation":[{"name":"Attoquant Diagnostics GmbH , Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machelle D.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Attoquant Diagnostics GmbH , Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Sunshine","sequence":"additional","affiliation":[{"name":"Colorado State University College of Veterinary Medicine and Biomedical Sciences Department of Clinical Sciences, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Brunk","sequence":"additional","affiliation":[{"name":"Colorado State University College of Veterinary Medicine and Biomedical 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