TY - JOUR
T1 - Methyl-γ-butyrobetaine decreases levels of acylcarnitines and attenuates the development of atherosclerosis
AU - Vilskersts, Reinis
AU - Kuka, Janis
AU - Liepinsh, Edgars
AU - Makrecka-Kuka, Marina
AU - Volska, Kristine
AU - Makarova, Elina
AU - Sevostjanovs, Eduards
AU - Cirule, Helena
AU - Grinberga, Solveiga
AU - Dambrova, Maija
N1 - Funding Information:
This work was supported by the ERDF grant [ 2DP/2.1.1.1/13/APIA/VIAA/003 ]. We thank JSC Grindeks (Riga, Latvia) for the supply of methyl-GBB and methyl-GBB phosphate.
Publisher Copyright:
© 2015 Elsevier Inc..
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Objective: The elevation of the levels of l-carnitine and its fatty acid esters, acylcarnitines, in tissue or plasma has been linked to the development of atherosclerosis. Recently, a potent inhibitor of l-carnitine biosynthesis and transport, methyl-γ-butyrobetaine (methyl-GBB), was discovered. In this study, we evaluated the effects of γ-butyrobetaine (GBB), l-carnitine and methyl-GBB administration on the progression of atherosclerosis. Methods: Apolipoprotein E knockout (apoE-/-) mice were treated with methyl-GBB, l-carnitine or GBB for 4months. Following the treatment, the amount of atherosclerotic lesions, the number of immune cells in atherosclerotic lesions and the plasma lipid profile were analysed. The l-carnitine and acylcarnitine levels were determined in the aortic tissues of CD-1 outbred mice 2weeks after treatment with methyl-GBB at the dose of 10mg/kg. Results: Treatment with methyl-GBB decreased the acylcarnitine and l-carnitine levels in the aortic tissues by seventeen- and ten-fold, respectively. Methyl-GBB treatment at a dose of 10. mg/kg reduced the size of atherosclerotic plaques by 36%. Neither l-carnitine nor GBB treatment affected the development of atherosclerosis. Conclusions: Methyl-GBB administration significantly attenuated the development of atherosclerosis in apoE-/-mice. Our results demonstrate that decreasing the acylcarnitine pools can attenuate the development of atherosclerosis.
AB - Objective: The elevation of the levels of l-carnitine and its fatty acid esters, acylcarnitines, in tissue or plasma has been linked to the development of atherosclerosis. Recently, a potent inhibitor of l-carnitine biosynthesis and transport, methyl-γ-butyrobetaine (methyl-GBB), was discovered. In this study, we evaluated the effects of γ-butyrobetaine (GBB), l-carnitine and methyl-GBB administration on the progression of atherosclerosis. Methods: Apolipoprotein E knockout (apoE-/-) mice were treated with methyl-GBB, l-carnitine or GBB for 4months. Following the treatment, the amount of atherosclerotic lesions, the number of immune cells in atherosclerotic lesions and the plasma lipid profile were analysed. The l-carnitine and acylcarnitine levels were determined in the aortic tissues of CD-1 outbred mice 2weeks after treatment with methyl-GBB at the dose of 10mg/kg. Results: Treatment with methyl-GBB decreased the acylcarnitine and l-carnitine levels in the aortic tissues by seventeen- and ten-fold, respectively. Methyl-GBB treatment at a dose of 10. mg/kg reduced the size of atherosclerotic plaques by 36%. Neither l-carnitine nor GBB treatment affected the development of atherosclerosis. Conclusions: Methyl-GBB administration significantly attenuated the development of atherosclerosis in apoE-/-mice. Our results demonstrate that decreasing the acylcarnitine pools can attenuate the development of atherosclerosis.
KW - Acylcarnitine
KW - Atherosclerosis
KW - L-Carnitine
KW - Methyl-GBB
UR - http://www.scopus.com/inward/record.url?scp=84939572140&partnerID=8YFLogxK
U2 - 10.1016/j.vph.2015.05.005
DO - 10.1016/j.vph.2015.05.005
M3 - Article
C2 - 25989106
AN - SCOPUS:84939572140
SN - 1537-1891
VL - 72
SP - 101
EP - 107
JO - Vascular Pharmacology
JF - Vascular Pharmacology
ER -