Abstract: ObjectiveTo explore the effect of betaine supplementation against high S-adenoslhomocysteine (SAH)-induced atherosclerosis (AS).MethodsDietary supplementation of high methionine and SAH hydrolase inhibitor was used to establish a model of high SAH-induced AS in apoE-deficient (apoE^-/-) mice.The mice with high plasma SAH level were treated with betaine at three different doses.After 8 and 16 weeks' betaine treatment,blood samples of the mice were collected to measure serum lipids levels,plasma SAH,S-adenoslmethionine (SAM),and homocysteine (Hcy) concentrations.The hearts of apoE^-/- mice were examined to assess the AS plaque area by staining with oil red O.ResultsCompared with the control group,the mice of high SAH group showed increased plasma SAH concentration(78.61±4.62 nmol/L),decreased SAM concentration (40.17±3.02 nmol/L),and decreased SAM/SAH ratio (0.65±0.11);there was no significant change in Hcy concentration (6.97±0.51μmol/L),while there were increases in absolute plaque area (52.65±8.40 mm²) and relative AS plaque area (25.47±5.23%) in the mice of high SAH group.Compared with high SAH group,the mice with high-dose betaine supplementation had significantly decreased plasma SAH (30.18±3.85 nmol/L) and Hcy (4.91±0.30μmol/L),increased SAM (78.14±3.99 nmol/L) and SAM/SAH ratio (2.78±0.34),and reduced high SAH-induced absolute AS plaque area (28.75±7.24)mm² and relative AS plaque area (13.89±3.96%),in a dose-response dependent manner.ConclusionBetaine supplementation could signifi-cantly decrease high plasma SAH level and reduce high SAH-induced AS plaque area in apoE^-/- mice.