Mildronate, a regulator of energy metabolism, reduces atherosclerosis in apoE/LDLR mice

Reinis Vilskersts, Edgars Liepinsh, Lukasz Mateuszuk, Solveiga Grinberga, Ivars Kalvinsh, Stefan Chlopicki, Maija Dambrova

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Background/Aims: Mildronate, an inhibitor of L-carnitine biosynthesis and transport, is used in clinics as a modulator of cellular energy metabolism and is a cardioprotective drug. L-Carnitine is a pivotal molecule in fatty acid oxidation pathways and its regulation in vasculature might be a promising approach for antiatherosclerotic treatment. This study was performed to evaluate the effects of mildronate treatment on the progression of atherosclerosis and the content of L-carnitine in the vascular wall. Methods: ApoE/LDLR -/- mice received mildronate at doses of 30 and 100 mg/kg for 4 months. Lipid profile was measured in plasma and atherosclerotic lesions were analyzed in whole aorta and aortic sinus. L-Carnitine concentration was assessed in rat aortic tissues after 2 weeks of treatment with mildronate at a dose of 100 mg/kg. Results: The chronic treatment with mildronate at a dose of 100 mg/kg significantly reduced the size of atherosclerotic plaques in the aortic roots and in the whole aorta, and slightly decreased the free cholesterol level. In addition, mildronate treatment decreased L-carnitine concentration in rat aortic tissues. Conclusions: Long-term mildronate treatment decreases L-carnitine content in aortic tissues and attenuates the development of atherosclerosis in apoE/LDLR-/- mice.

Original languageEnglish
Pages (from-to)287-293
Number of pages7
JournalPharmacology
Volume83
Issue number5
DOIs
Publication statusPublished - May 2009
Externally publishedYes

Keywords

  • ApoE/LDLR mice
  • Atherosclerosis
  • Energy metabolism
  • L-Carnitine
  • Mildronate

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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