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- Title
Diminazene Aceturate Stabilizes Atherosclerotic Plaque and Attenuates Hepatic Steatosis in apoE-Knockout Mice by Influencing Macrophages Polarization and Taurine Biosynthesis.
- Authors
Stachowicz, Aneta; Wiśniewska, Anna; Kuś, Katarzyna; Białas, Magdalena; Łomnicka, Magdalena; Totoń-Żurańska, Justyna; Kiepura, Anna; Stachyra, Kamila; Suski, Maciej; Bujak-Giżycka, Beata; Jawień, Jacek; Olszanecki, Rafał
- Abstract
Atherosclerosis and nonalcoholic fatty liver disease are leading causes of morbidity and mortality in the Western countries. The renin–angiotensin system (RAS) with its two main opposing effectors, i.e., angiotensin II (Ang II) and Ang-(1–7), 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-(1–7) and thus favors Ang-(1–7) 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−/− mice fed a high-fat diet (HFD). We have shown that DIZE stabilized atherosclerotic lesions and attenuated hepatic steatosis in apoE−/− mice fed an HFD. Such effects were associated with decreased total macrophages content and increased α-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−/− mice. However, exact molecular mechanisms of both anti-atherosclerotic and anti-steatotic actions of DIZE require further investigations.
- Subjects
FATTY liver; NON-alcoholic fatty liver disease; ATHEROSCLEROTIC plaque; MACROPHAGES; ANGIOTENSIN converting enzyme; AMYLOID plaque
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 11, p5861
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22115861