Diminazene aceturate (DIZE) stabilizes atherosclerotic plaques and attenuates hepatic steatosis in apolipoprotein E knockout mice by influencing macrophages polarization and taurine biosynthesis

ABSTRACT: Atherosclerosis and nonalcoholic fatty liver disease (NAFLD) are leading causes of morbidity and mortality in the Western countries. NAFLD is an important independent risk factor for the development of atherosclerosis. The renin-angiotensin system (RAS) with its two main opposing effectors: 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 at a dose of 30 mg/kg/day given orally for 16 weeks was able to stabilize atherosclerotic lesions and attenuate 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 atherosclerotic lesions. Interestingly, the anti-steatotic action of DIZE in the liver was related to the elevated HDL in the plasma, decreased triglycerides levels and increased biosynthesis and concentration of taurine in liver of apoE-/- mice. However, the exact molecular mechanisms of both the anti-atherosclerotic and anti-steatotic actions of DIZE require further investigations.

INSTRUMENT(S): LTQ

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Aortic Atherosclerosis,Fatty Liver Disease

SUBMITTER: Aneta Stachowicz  

LAB HEAD: Rafał Olszanecki

PROVIDER: PXD022829 | Pride | 2021-09-09

REPOSITORIES: Pride