Evaluation of mild hyperhomocysteinemia during the development of atherosclerosis in apolipoprotein E-deficient and normal mice

• Published in: Experimental and molecular pathology 2011-02, Vol.90 (1), p.45-50
• Main Authors: Aléssio, Ana C.M., Santos, Célio X.C., Debbas, Victor, Oliveira, Laurione C., Haddad, Renato, Annichino-Bizzacchi, Joyce M.
• Format: Article
• Language: English
• Subjects: Animals; Apolipoprotein E-deficient mice; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - complications; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Diet; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - pathology; Folate; Folic Acid - pharmacology; Hyperhomocysteinemia; Hyperhomocysteinemia - chemically induced; Hyperhomocysteinemia - complications; Hyperhomocysteinemia - physiopathology; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Methionine - pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; Normal mice (C57BL/6); Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Time Factors
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2010.07.008

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.