Evaluation of mild hyperhomocysteinemia during the development of atherosclerosis in apolipoprotein E-deficient and normal mice.
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.
Aléssio
Ana C M
AC
Hematology-Hemotherapy Center, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil. alessio@bol.com.br
Santos
Célio X C
CX
Debbas
Victor
V
Oliveira
Laurione C
LC
Haddad
Renato
R
Annichino-Bizzacchi
Joyce M
JM
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
D001057:Apolipoproteins E; D005492:Folic Acid; D008715:Methionine