{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T23:00:47Z","timestamp":1774652447321,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20SFRN35200003"],"award-info":[{"award-number":["20SFRN35200003"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["R01HL122863"],"award-info":[{"award-number":["R01HL122863"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["R01HL167087"],"award-info":[{"award-number":["R01HL167087"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["20SFRN35200003"],"award-info":[{"award-number":["20SFRN35200003"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL122863"],"award-info":[{"award-number":["R01HL122863"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL167087"],"award-info":[{"award-number":["R01HL167087"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Therapeutic efficacy of histidyl dipeptides such as carnosine is hampered by circulating carnosinase-1 (CN1), which catalyzes carnosine\u2019s hydrolysis and degradation. Prior reports suggest that oral carnosine may improve cardiometabolic parameters in patients with heart failure (HF), but whether CN1 activity is affected by HF is unknown. Here, we measured CN1 content and carnosine degradation rate (CDR) in preoperative plasma samples from a cohort of patients (n = 138) undergoing elective cardiac surgery to determine whether plasma CN1 and\/or CDR varied with left ventricular (LV) systolic dysfunction. CN1 content was normally distributed in the cohort, but plasma CDR displayed a quasi-bimodal distribution into high- (&gt;2 nmol\/(h*\u03bcL)) and low-activity (\u22642 nmol\/(h*\u03bcL)) clusters. Multivariable analysis confirmed female sex, diabetes and LV systolic dysfunction was associated with the low-activity CDR cluster. Although CN1 content did not differ, logistic regression analysis revealed that CDR and CN1-specific activity (CDR\/CN1 content) was significantly lower in patients with both moderate (ejection fraction, EF \u2265 35 to &lt;50%) and severe LV systolic dysfunction (EF &lt; 35%) compared with patients in the normal range (EF \u2265 50%). These findings suggest that plasma CN1 activity is regulated by factors independent of expression, and that a decline in LV systolic function is associated with low CN1 activity. Further studies are needed to delineate specific mechanisms controlling CN1 expression and activity, which will facilitate the development of carnosine and other histidyl dipeptide therapies for cardiometabolic disorders such as HF.<\/jats:p>","DOI":"10.3390\/ijms26062608","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T04:29:18Z","timestamp":1741926558000},"page":"2608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Low Plasma Carnosinase-1 Activity in Patients with Left Ventricular Systolic Dysfunction: Implications for Carnosine Therapy in Heart Failure"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-333X","authenticated-orcid":false,"given":"I-Chau","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ettore","family":"Gilardoni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2987-458X","authenticated-orcid":false,"given":"Islam A.","family":"Berdaweel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Department of Clinical Pharmacy and Pharmacy Practice, Yarmouk University, Irbid 21163, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Knute D.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-8875","authenticated-orcid":false,"given":"Ethan J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35554","DOI":"10.1074\/jbc.M607305200","article-title":"Redox regulation of 4-hydroxy-2-nonenal-mediated endothelial barrier dysfunction by focal adhesion, adherens, and tight junction proteins","volume":"281","author":"Usatyuk","year":"2006","journal-title":"J. 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