title: Methyl-γ-butyrobetaine decreases levels of acylcarnitines and attenuates the development of atherosclerosis.
abstract: 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 10mg/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.
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia; Rigas Stradins University, Dzirciema Str. 16, Riga LV-1007, Latvia. Electronic address: Reinis.Vilskersts@biomed.lu.lv.
authors.forename: Reinis
authors.initials: R
authors.lastname: Vilskersts
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors.forename: Janis
authors.initials: J
authors.lastname: Kuka
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors.forename: Edgars
authors.initials: E
authors.lastname: Liepinsh
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia; Rigas Stradins University, Dzirciema Str. 16, Riga LV-1007, Latvia.
authors.forename: Marina
authors.initials: M
authors.lastname: Makrecka-Kuka
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors.forename: Kristine
authors.initials: K
authors.lastname: Volska
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors.forename: Elina
authors.initials: E
authors.lastname: Makarova
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors.forename: Eduards
authors.initials: E
authors.lastname: Sevostjanovs
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors.forename: Helena
authors.initials: H
authors.lastname: Cirule
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia.
authors.forename: Solveiga
authors.initials: S
authors.lastname: Grinberga
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia; Rigas Stradins University, Dzirciema Str. 16, Riga LV-1007, Latvia.
authors.forename: Maija
authors.initials: M
authors.lastname: Dambrova
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism*; D001622:Betaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D008297:Male; D051379:Mice
chemical_list: D001057:Apolipoproteins E; C116917:acylcarnitine; D001622:Betaine; C002889:gamma-butyrobetaine; D002331:Carnitine
keywords: Acylcarnitine; Atherosclerosis; Methyl-GBB; l-Carnitine