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Anti-Atherosclerotic Action of Agmatine in ApoE-Knockout Mice

Department of Pharmacology, Jagiellonian University Medical College, 31-531 Krakow, Poland
Department of Histology, Jagiellonian University Medical College, 31-034 Krakow, Poland
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(8), 1706;
Received: 10 July 2017 / Revised: 31 July 2017 / Accepted: 1 August 2017 / Published: 4 August 2017
(This article belongs to the Special Issue Pathomechanisms of Atherosclerosis. Part I)
Atherosclerosis is an inflammatory disease in which dysfunction of mitochondria play an important role, and disorders of lipid management intensify this process. Agmatine, an endogenous polyamine formed by decarboxylation of arginine, exerts a protective effect on mitochondria and modulates fatty acid metabolism. We investigated the effect of exogenous agmatine on the development of atherosclerosis and changes in lipid profile in apolipoprotein E knockout (apoE-/-) mice. Agmatine caused an approximate 40% decrease of atherosclerotic lesions, as estimated by en face and cross-section methods with an influence on macrophage but not on smooth muscle content in the plaques. Agmatine treatment did not changed gelatinase activity within the plaque area. What is more, the action of agmatine was associated with an increase in the number of high density lipoproteins (HDL) in blood. Real-Time PCR analysis showed that agmatine modulates liver mRNA levels of many factors involved in oxidation of fatty acid and cholesterol biosynthesis. Two-dimensional electrophoresis coupled with mass spectrometry identified 27 differentially expressed mitochondrial proteins upon agmatine treatment in the liver of apoE-/- mice, mostly proteins related to metabolism and apoptosis. In conclusion, prolonged administration of agmatine inhibits atherosclerosis in apoE-/- mice; however, the exact mechanisms linking observed changes and elevations of HDL plasma require further investigation. View Full-Text
Keywords: atherosclerosis; agmatine; apoE-knockout mice; fatty liver metabolism atherosclerosis; agmatine; apoE-knockout mice; fatty liver metabolism
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Wiśniewska, A.; Olszanecki, R.; Totoń-Żurańska, J.; Kuś, K.; Stachowicz, A.; Suski, M.; Gębska, A.; Gajda, M.; Jawień, J.; Korbut, R. Anti-Atherosclerotic Action of Agmatine in ApoE-Knockout Mice. Int. J. Mol. Sci. 2017, 18, 1706.

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