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

Pharmacology. 2009;83(5):287-93. doi: 10.1159/000210015. Epub 2009 Mar 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / metabolism*
  • Aorta / pathology*
  • Atherosclerosis / drug therapy*
  • Betaine / analogs & derivatives
  • Betaine / metabolism
  • Cardiovascular Agents / pharmacokinetics
  • Cardiovascular Agents / pharmacology*
  • Carnitine / metabolism
  • Energy Metabolism / drug effects*
  • Female
  • Lipids / blood
  • Male
  • Methylhydrazines / pharmacokinetics
  • Methylhydrazines / pharmacology*
  • Mice
  • Mice, Knockout
  • Rats
  • Rats, Wistar

Substances

  • Cardiovascular Agents
  • Lipids
  • Methylhydrazines
  • Betaine
  • gamma-butyrobetaine
  • 3-(2,2,2-trimethylhydrazine)propionate
  • Carnitine