{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T11:39:44Z","timestamp":1765280384118,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T00:00:00Z","timestamp":1696032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Leipzig University","award":["501100008678"],"award-info":[{"award-number":["501100008678"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A restoration of low homoarginine (hArg) levels in obese ZSF1 rats (O-ZSF1) before (S1-ZSF1) and after (S2-ZSF1) the manifestation of heart failure with preserved ejection fraction (HFpEF) did not affect the worsening of cardiac HFpEF characteristics. Here, potential regulation of key enzymes of arginine metabolism in other organs was analyzed. Arginase 2 (ARG2) was reduced &gt;35% in the kidney and small intestine of hArg-supplemented rats compared to O-ZSF1. Glycine amidinotransferase (GATM) was 29% upregulated in the kidneys of S1-ZSF1. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) levels were reduced &gt;50% in the livers of O-ZSF1 but restored in S2-ZSF1 compared to healthy rats (L-ZSF1). In the skeletal muscle, iNOS was lower in O-ZSF1 and further decreased in S1-ZSF1 and S2-ZSF1 compared to L-ZSF1. iNOS levels were lower in the liver of the S2-ZSF1 group but higher in the kidneys of S1-ZSF1 compared to L-ZSF1. Supplementation with hArg in an in vivo HFpEF model resulted in the inhibition of renal ARG2 and an increase in GATM expression. This supplementation might contribute to the stabilization of intestinal iNOS and ARG2 imbalances, thereby enhancing barrier function. Additionally, it may offer protective effects in skeletal muscle by downregulating iNOS. In the conceptualization of hArg supplementation studies, the current disease progression stage as well as organ-specific enzyme regulation should be considered.<\/jats:p>","DOI":"10.3390\/ijms241914782","type":"journal-article","created":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T16:57:06Z","timestamp":1696179426000},"page":"14782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Systemic Effects of Homoarginine Supplementation on Arginine Metabolizing Enzymes in Rats with Heart Failure with Preserved Ejection Fraction"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0799-4725","authenticated-orcid":false,"given":"Petra","family":"B\u00fcttner","sequence":"first","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at University of Leipzig, 04289 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6677-846X","authenticated-orcid":false,"given":"Sarah","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at University of Leipzig, 04289 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"B\u00f6ttner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at University of Leipzig, 04289 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-3126","authenticated-orcid":false,"given":"Susann","family":"Ossmann","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Heart Center Leipzig at University of Leipzig, 04289 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3597-6276","authenticated-orcid":false,"given":"Edzard","family":"Schwedhelm","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0169-998X","authenticated-orcid":false,"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at University of Leipzig, 04289 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/j.1440-1681.2007.04638.x","article-title":"Arginase: A critical regulator of nitric oxide synthesis and vascular function","volume":"34","author":"Durante","year":"2007","journal-title":"Clin. 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