PMID- 23754667 OWN - NLM STAT- MEDLINE DCOM- 20140516 LR - 20131004 IS - 1613-4133 (Electronic) IS - 1613-4125 (Linking) VI - 57 IP - 10 DP - 2013 Oct TI - Methionine-induced hyperhomocysteinemia impairs the antioxidant ability of high-density lipoproteins without reducing in vivo macrophage-specific reverse cholesterol transport. PG - 1814-24 LID - 10.1002/mnfr.201300133 [doi] AB - SCOPE: High plasma homocysteine concentrations have been associated with increased risk of cardiovascular disease both in humans and experimental animal models, whereas plasma HDL-cholesterol concentration is inversely correlated with such disorders. This work aimed to study the impact of methionine-induced hyperhomocysteinemia (HHcy) on two major antiatherogenic functions of HDL, namely their capacity to prevent LDL oxidation and induce in vivo macrophage-specific reverse cholesterol transport. METHODS AND RESULTS: Methionine-induced HHcy in mice resulted in an approximately 20% decreased concentration of HDL-cholesterol and HDL main protein component, apolipoprotein A-I. The HDL potential to resist oxidation as well as to prevent LDL oxidative modification was impaired in hyperhomocysteinemic mice. Activities of paraoxonase-1 and platelet activation factor acetylhydrolase, two of the main HDL-associated enzymes with antioxidant activity, were reduced. The ability of HDL to efflux cholesterol from macrophages was decreased in hyperhomocysteinemic mice; however, the in vivo macrophage-specific reverse cholesterol transport measured as the output of labeled cholesterol into feces did not significantly differ between groups. CONCLUSION: Our data indicate that the HDL from methionine-induced hyperhomocysteinemic mice was more prone to oxidation and displayed lower capacity to protect LDL against oxidative modification than that of control mice, highlighting a mechanism by which a diet-induced HHcy may facilitate progression of atherosclerosis. CI - (c) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Julve, Josep AU - Julve J AD - Institut d'Investigacions Biomediques Sant Pau (IIB-Sant Pau), Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabolicas Asociadas, CIBERDEM, Spain. FAU - Escola-Gil, Joan C AU - Escola-Gil JC FAU - Rodriguez-Millan, Elisabeth AU - Rodriguez-Millan E FAU - Martin-Campos, Jesus M AU - Martin-Campos JM FAU - Jauhiainen, Matti AU - Jauhiainen M FAU - Quesada, Helena AU - Quesada H FAU - Renteria-Obregon, Ivy M AU - Renteria-Obregon IM FAU - Osada, Jesus AU - Osada J FAU - Sanchez-Quesada, Jose L AU - Sanchez-Quesada JL FAU - Blanco-Vaca, Francisco AU - Blanco-Vaca F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130610 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 RN - 0 (Antioxidants) RN - 0 (Apolipoprotein A-I) RN - 0 (Cholesterol, HDL) RN - 0LVT1QZ0BA (Homocysteine) RN - AE28F7PNPL (Methionine) RN - EC 3.1.8.1 (Aryldialkylphosphatase) RN - Homocysteinemia SB - IM MH - Animals MH - Antioxidants/*metabolism MH - Apolipoprotein A-I/blood MH - Aryldialkylphosphatase/blood MH - Atherosclerosis/pathology MH - Biological Transport MH - Cell Line MH - Cholesterol, HDL/*antagonists & inhibitors/blood MH - Disease Models, Animal MH - Female MH - Homocysteine/blood MH - Hyperhomocysteinemia/*chemically induced/complications/pathology MH - Lipid Metabolism/drug effects MH - Liver/drug effects/metabolism MH - Macrophages/*metabolism MH - Male MH - Methionine/administration & dosage/*adverse effects MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic OTO - NOTNLM OT - HDL OT - Homocysteine OT - Hyperhomocysteinemia OT - Methionine OT - Oxidation OT - Reverse cholesterol transport EDAT- 2013/06/12 06:00 MHDA- 2014/05/17 06:00 CRDT- 2013/06/12 06:00 PHST- 2013/02/20 00:00 [received] PHST- 2013/03/26 00:00 [revised] PHST- 2013/03/31 00:00 [accepted] PHST- 2013/06/12 06:00 [entrez] PHST- 2013/06/12 06:00 [pubmed] PHST- 2014/05/17 06:00 [medline] AID - 10.1002/mnfr.201300133 [doi] PST - ppublish SO - Mol Nutr Food Res. 2013 Oct;57(10):1814-24. doi: 10.1002/mnfr.201300133. Epub 2013 Jun 10.