title: Evaluation of mild hyperhomocysteinemia during the development of atherosclerosis in apolipoprotein E-deficient and normal mice.
abstract: We focused on the effect of mild hyperhomocysteinemia (HHcy) on the development of atherosclerosis, using apolipoprotein E-deficient (apoE(-/-)) and normal mice. Mice received diets enriched in methionine with low or high levels of folate, B(12) and B(6) (diets B and C, respectively), and diet only with low levels of folate, B(12) and B(6) (diets D), to induce mild HHcy. Normal mice fed on diets B, C and D presented mild HHcy, but they did not develop atherosclerotic lesions after 24 weeks of diet. In addition, increased endoplasmic reticulum stress was present in normal mice fed on diet B, compared to others groups. ApoE(-/-) mice fed on diet B for 20 weeks presented the greatest atherosclerotic lesion area at the aortic sinus than other groups. These results suggest that the methionine may have a toxic effect on endothelium, and the B-vitamins addition on diet may have a protective effect in the long term, despite the increase on homocysteine levels. Mild HHcy accelerated the development of atherosclerosis in apoE(-/-) mice, and supplementation with B-vitamins is important for prevention of vascular disease, principally in the long term.
authors.affiliation: Hematology-Hemotherapy Center, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil. alessio@bol.com.br
authors.forename: Ana C M
authors.initials: AC
authors.lastname: Aléssio
authors.forename: Célio X C
authors.initials: CX
authors.lastname: Santos
authors.forename: Victor
authors.initials: V
authors.lastname: Debbas
authors.forename: Laurione C
authors.initials: LC
authors.lastname: Oliveira
authors.forename: Renato
authors.initials: R
authors.lastname: Haddad
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications* / Q000473:pathology / Q000517:prevention & control; D004032:Diet; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology; D005492:Folic Acid / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008715:Methionine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D005492:Folic Acid; D008715:Methionine