Journal
PHARMACOLOGY
Volume 83, Issue 5, Pages 287-293Publisher
KARGER
DOI: 10.1159/000210015
Keywords
Mildronate; Atherosclerosis; Energy metabolism; L-Carnitine; ApoE/LDLR-/- mice
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Funding
- European Social Foundation (ESF)
- Latvian Science Council
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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. Copyright (C) 2009 S. Karger AG, Basel
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