6533b827fe1ef96bd1286d9a

RESEARCH PRODUCT

Mildronate, a Regulator of Energy Metabolism, Reduces Atherosclerosis in apoE/LDLR<sup>–/–</sup> Mice

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<i>Background/Aims:</i> Mildronate, an inhibitor of <i>L</i>-carnitine biosynthesis and transport, is used in clinics as a modulator of cellular energy metabolism and is a cardioprotective drug. <i>L</i>-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 <i>L</i>-carnitine in the vascular wall. <i>Methods:</i> ApoE/LDLR<sup>–/–</sup> 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. <i>L</i>-Carnitine concentration was assessed in rat aortic tissues after 2 weeks of treatment with mildronate at a dose of 100 mg/kg. <i>Results:</i> 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 <i>L</i>-carnitine concentration in rat aortic tissues. <i>Conclusions:</i> Long-term mildronate treatment decreases <i>L</i>-carnitine content in aortic tissues and attenuates the development of atherosclerosis in apoE/LDLR<sup>–/–</sup> mice.