Mildronate, a regulator of energy metabolism, reduces atherosclerosis in apoE/LDLR-/- mice.
OBJECTIVE
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.
Vilskersts
Reinis
R
University of Latvia, Riga, Latvia. reinis.vilskersts@biomed.lu.lv
Liepinsh
Edgars
E
Mateuszuk
Lukasz
L
Grinberga
Solveiga
S
Kalvinsh
Ivars
I
Chlopicki
Stefan
S
Dambrova
Maija
M