{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:26:49Z","timestamp":1780410409946,"version":"3.54.1"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,30]],"date-time":"2021-05-30T00:00:00Z","timestamp":1622332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre (NCN)","award":["2017\/26\/D\/NZ4\/00480"],"award-info":[{"award-number":["2017\/26\/D\/NZ4\/00480"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atherosclerosis and nonalcoholic fatty liver disease are leading causes of morbidity and mortality in the Western countries. The renin\u2013angiotensin system (RAS) with its two main opposing effectors, i.e., angiotensin II (Ang II) and Ang-(1\u20137), is widely recognized as a major regulator of cardiovascular function and body metabolic processes. Angiotensin-converting enzyme 2 (ACE2) by breaking-down Ang II forms Ang-(1\u20137) and thus favors Ang-(1\u20137) actions. Therefore, the aim of our study was to comprehensively evaluate the influence of prolonged treatment with ACE2 activator, diminazene aceturate (DIZE) on the development of atherosclerotic lesions and hepatic steatosis in apoE\u2212\/\u2212 mice fed a high-fat diet (HFD). We have shown that DIZE stabilized atherosclerotic lesions and attenuated hepatic steatosis in apoE\u2212\/\u2212 mice fed an HFD. Such effects were associated with decreased total macrophages content and increased \u03b1-smooth muscle actin levels in atherosclerotic plaques. Moreover, DIZE changed polarization of macrophages towards increased amount of anti-inflammatory M2 macrophages in the atherosclerotic lesions. Interestingly, the anti-steatotic action of DIZE in the liver was related to the elevated levels of HDL in the plasma, decreased levels of triglycerides, and increased biosynthesis and concentration of taurine in the liver of apoE\u2212\/\u2212 mice. However, exact molecular mechanisms of both anti-atherosclerotic and anti-steatotic actions of DIZE require further investigations.<\/jats:p>","DOI":"10.3390\/ijms22115861","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:22:15Z","timestamp":1622420535000},"page":"5861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Diminazene Aceturate Stabilizes Atherosclerotic Plaque and Attenuates Hepatic Steatosis in apoE-Knockout Mice by Influencing Macrophages Polarization and Taurine Biosynthesis"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1582-7065","authenticated-orcid":false,"given":"Aneta","family":"Stachowicz","sequence":"first","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7370-9879","authenticated-orcid":false,"given":"Anna","family":"Wi\u015bniewska","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Ku\u015b","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Bia\u0142as","sequence":"additional","affiliation":[{"name":"Chair of Pathomorphology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"\u0141omnicka","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5970-238X","authenticated-orcid":false,"given":"Justyna","family":"Toto\u0144-\u017bura\u0144ska","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-7221","authenticated-orcid":false,"given":"Anna","family":"Kiepura","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Stachyra","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7575-2184","authenticated-orcid":false,"given":"Maciej","family":"Suski","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Bujak-Gi\u017cycka","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9831-8655","authenticated-orcid":false,"given":"Jacek","family":"Jawie\u0144","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa\u0142","family":"Olszanecki","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1161\/CIRCULATIONAHA.109.849166","article-title":"Cardiovascular Risk Prediction: Basic Concepts, Current Status, and Future Directions","volume":"121","year":"2010","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1161\/01.ATV.20.5.1262","article-title":"Lessons from Sudden Coronary Death: A Comprehensive Morphological Classification Scheme for Atherosclerotic Lesions","volume":"20","author":"Virmani","year":"2000","journal-title":"Arter. 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