Methyl-γ-butyrobetaine decreases levels of acylcarnitines and attenuates the development of atherosclerosis

Reinis Vilskersts, Janis Kuka, Edgars Liepinsh, Marina Makrecka-Kuka, Kristine Volska, Elina Makarova, Eduards Sevostjanovs, Helena Cirule, Solveiga Grinberga, Maija Dambrova

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Objective: The elevation of the levels of l-carnitine and its fatty acid esters, acylcarnitines, in tissue or plasma has been linked to the development of atherosclerosis. Recently, a potent inhibitor of l-carnitine biosynthesis and transport, methyl-γ-butyrobetaine (methyl-GBB), was discovered. In this study, we evaluated the effects of γ-butyrobetaine (GBB), l-carnitine and methyl-GBB administration on the progression of atherosclerosis. Methods: Apolipoprotein E knockout (apoE-/-) mice were treated with methyl-GBB, l-carnitine or GBB for 4months. Following the treatment, the amount of atherosclerotic lesions, the number of immune cells in atherosclerotic lesions and the plasma lipid profile were analysed. The l-carnitine and acylcarnitine levels were determined in the aortic tissues of CD-1 outbred mice 2weeks after treatment with methyl-GBB at the dose of 10mg/kg. Results: Treatment with methyl-GBB decreased the acylcarnitine and l-carnitine levels in the aortic tissues by seventeen- and ten-fold, respectively. Methyl-GBB treatment at a dose of 10. mg/kg reduced the size of atherosclerotic plaques by 36%. Neither l-carnitine nor GBB treatment affected the development of atherosclerosis. Conclusions: Methyl-GBB administration significantly attenuated the development of atherosclerosis in apoE-/-mice. Our results demonstrate that decreasing the acylcarnitine pools can attenuate the development of atherosclerosis.

Original languageEnglish
Pages (from-to)101-107
Number of pages7
JournalVascular Pharmacology
Volume72
DOIs
Publication statusPublished - 1 Sep 2015

Keywords*

  • Acylcarnitine
  • Atherosclerosis
  • L-Carnitine
  • Methyl-GBB

Field of Science*

  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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