高同型半胱氨酸血症
同型半胱氨酸
内科学
内分泌学
蛋氨酸
维生素
载脂蛋白B
生物
载脂蛋白E
B族维生素
医学
生物化学
胆固醇
氨基酸
疾病
作者
Ji Zhou,Jan Møller,Merel Ritskes‐Hoitinga,Mogen L Larsen,Richard C. Austin,Erling Falk
标识
DOI:10.1016/s0021-9150(03)00138-2
摘要
It has been demonstrated that hyperhomocysteinemia (HHcy) accelerates atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice. In this study, vitamin-defined chow diets were used to induce HHcy in apoE(-/-) mice in an attempt to identify possible pathogenic pathways. Six-week-old female apoE(-/-) mice were divided into seven groups: vitamin-defined purified chow diet alone (control), or same diet supplemented with either D,L-homocysteine (upward arrow Hcy) or L-homocystine (upward arrow Hcy-Hcy), or diet high in L-methionine (upward arrow Met), or diet high in B-vitamins (upward arrow vitamin), or diets deficient in folate (downward arrow folate) or vitamin B(6) ( downward arrow B(6)). Eighteen weeks later, plasma total homocysteine (tHcy), lipids and atherosclerotic plaque burden (aortic root, aortic arch, and brachiocephalic trunk) were measured. tHcy levels were similar in the upward arrow vitamin, downward arrow folate, downward arrow B(6) and control groups (9.2-10.1 micromol/l, NS), but elevated mildly in the upward arrow Hcy-Hcy group (16.1 micromol/l) and moderately in the upward arrow Met and upward arrow Hcy groups (53.6 and 51.5 micromol/l, respectively). Mice in the latter two groups had significantly more atherosclerosis in the aortic root. Although B vitamin-supplementation failed to lower tHcy levels, mice had less atherosclerosis in the aortic arch. In summary, dietary methionine and homocysteine, but not homocystine, enhanced the development of atherosclerosis. Supplementation with B vitamins appeared to confer homocysteine-independent protection against atherosclerosis. These results suggest that (1) there may be a threshold level below which homocysteine is not atherogenic; (2) the atherogenic effect of HHcy may be mediated via an intracellular pathway; and/or (3) the anti-atherogenic effect of B vitamins in normohomocysteinemic mice is independent of tHcy levels.
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