title: Methionine-induced hyperhomocysteinemia impairs the antioxidant ability of high-density lipoproteins without reducing in vivo macrophage-specific reverse cholesterol transport.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Julve
authors.forename: Joan C
authors.initials: JC
authors.lastname: Escolà-Gil
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rodríguez-Millán
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Martín-Campos
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Helena
authors.initials: H
authors.lastname: Quesada
authors.forename: Ivy M
authors.initials: IM
authors.lastname: Rentería-Obregón
authors.forename: Jesús
authors.initials: J
authors.lastname: Osada
authors.forename: José L
authors.initials: JL
authors.lastname: Sánchez-Quesada
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco-Vaca
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000097:blood; D043303:Aryldialkylphosphatase / Q000097:blood; D050197:Atherosclerosis / Q000473:pathology; D001692:Biological Transport; D002460:Cell Line; D008076:Cholesterol, HDL / Q000037:antagonists & inhibitors* / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D000975:Antioxidants; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D006710:Homocysteine; D008715:Methionine; D043303:Aryldialkylphosphatase
keywords: HDL; Homocysteine; Hyperhomocysteinemia; Methionine; Oxidation; Reverse cholesterol transport