Inhibition of monoamine oxidase B reduces atherosclerosis and fatty liver in mice.
Clin Sci (Lond)
; 137(1): 17-30, 2023 01 13.
Article
en En
| MEDLINE
| ID: mdl-36416117
ABSTRACT
Oxidative stress is vital for pathophysiology of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Monoamine oxidase (MAO) is an important source of oxidative stress in the vascular system and liver. However, the effect of MAO inhibition on atherosclerosis and NAFLD has not been explored. In the present study, MAO A and B expressions were increased in atherosclerotic plaques in human and apolipoprotein E (ApoE)-deficient mice. Inhibition of MAO B (by deprenyl), but not MAO A (by clorgyline), reduced the atheroma area in the thoracic aorta and aortic sinus in ApoE-deficient mice fed the cholesterol-enriched diet for 15 weeks. MAO B inhibition attenuated oxidative stress, expression of adhesion molecules, production of inflammatory cytokines, and macrophage infiltration in atherosclerotic plaques and decreased plasma triglyceride and low-density lipoprotein (LDL) cholesterol concentrations. MAO B inhibition had no therapeutic effect on restenosis in the femoral artery wire-induced injury model in C57BL/6 mice. In the NAFLD mouse model, MAO B inhibition reduced lipid droplet deposition in the liver and hepatic total cholesterol and triglyceride levels in C57BL/6 mice fed high-fat diets for 10 weeks. Key enzymes for triglyceride and cholesterol biosynthesis (fatty acid synthase and 3-hydroxy-3-methylglutaryl-CoA reductase, HMGCR) and inflammatory markers were inhibited, and cholesterol clearance was up-regulated (increased LDL receptor expression and reduced proprotein convertase subtilisin/kexin type 9, PCSK9, expression) by MAO B inhibition in the liver. These results were also demonstrated in the HepG2 liver cell model. Our data suggest that MAO B inhibition is a potential and novel treatment for atherosclerosis and NAFLD.
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Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Aterosclerosis
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Placa Aterosclerótica
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Enfermedad del Hígado Graso no Alcohólico
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Hipercolesterolemia
Límite:
Animals
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Humans
Idioma:
En
Revista:
Clin Sci (Lond)
Año:
2023
Tipo del documento:
Article
País de afiliación:
Taiwán