Department of Cardiology, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China.
J Geriatr Cardiol. 2014 Mar;11(1):74-8. doi: 10.3969/j.issn.1671-5411.2014.01.013.
Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocysteine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the formation of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice.
Forty-eight 7-week-old LDLr(-/-) mice were assigned to the following groups: mice fed a standard rodent diet (control group), mice fed a high-methionine diet (high-methionine group), mice fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed.
At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe.
Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLr(-/-) mice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.
高同型半胱氨酸血症是冠心病（CHD）的独立危险因素。然而，高同型半胱氨酸血症是否影响动脉粥样硬化的进展尚不清楚。在本研究中，我们研究了高同型半胱氨酸血症对低密度脂蛋白受体缺陷（LDLr（-/-））小鼠动脉粥样硬化形成的影响。
将 48 只 7 周龄 LDLr（-/-）小鼠分为以下 4 组：普通饮食组（对照组）、高蛋氨酸饮食组（高蛋氨酸组）、高脂饮食组（高脂组）和高蛋氨酸加高脂饮食组（高蛋氨酸和高脂组）。在 19、23 和 27 周时，每组各间隔处死 4 只小鼠。
在研究结束时，对照组的小鼠直到 27 周龄时主动脉窦和主动脉表面才出现动脉粥样硬化病变，但其他三组在 19 周时就出现了动脉粥样硬化病变。高蛋氨酸组主动脉表面的动脉粥样硬化病变少于高脂组（P<0.001）。高蛋氨酸和高脂组主动脉表面的动脉粥样硬化病变最严重。与主动脉表面的动脉粥样硬化病变相比，主动脉窦内动脉粥样硬化病变的平均面积在高蛋氨酸组中低于高脂组（P<0.001）。高蛋氨酸和高脂组主动脉窦内的动脉粥样硬化病变最严重。
同型半胱氨酸血症加速 LDLr（-/-）小鼠动脉粥样硬化病变的发生，并独立诱导早期动脉粥样硬化。降低同型半胱氨酸血症水平可能有利于 CHD 的预防和治疗。
