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Abdominal aortic aneurysm (AAA), defined as a 50% increase in external diameter of the abdominal aorta, is one of the leading causes of sudden death in aging men.Although hyperhomocysteinemia (HHcy) is a strong independent risk factor of coronary heart disease and stroke in human, the association of HHcy and AAA is still an enigma.We subcutaneously infused AngⅡ (1000 ng/kg/min) or saline into 16-week-old male ApoE-/-mice for 28 days to induce AAA.Before implanting, mice was fed with 0, 0.9 g/L, 1.8 g/L Hcy and 1.8 g/L Hcy+folic acid (0.071 g/g/day, equivalent to 5 mg/70 kg/day human dose) in drinking water for 4 weeks, and subsequent 28 days together with AngⅡ or saline infusion.Homocysteine supplement at 0, 0.9 g/L or 1.8 g/L in ApoE-/-mice resulted in 8.12±2.58 M, 16.24±4.48 M or 23.52±3.53 M of plasma bomocysteine level respectively.Although the effect of 0.9 g/L homocysteine treatment did not reach statistical significance compared to that of no homocysteine supplement.Intriguingly, supplementation of folic acid in homocysteine (1.8 g/L) treated and AngⅡ infused ApoE-/-mice resulted in a greatly diminished incidence and severity of HHcy aggravated AAA (folic acid+Hcy+AngⅡ vs.Hcy+AngⅡ: 50% vs.92.3%, P<0.05).Moreover, folic acid treatment dramatically reduced the maximal abdominal aortic diameter, elastin degradation, inflammatory cell infiltration and MCP-1/IL-6 production in the adventitia of suprarenal aorta.These data suggested that homocysteine lowering by folic acid rescued HHcy aggravated AngⅡ-induced AAA formation.It may provide us a new therapeutic strategy for preventing AAA formation.