动脉粥样硬化发生发展的机制复杂且未完全明确。越来越多的研究表明镉能够影响动脉粥样硬化的发生发展，是动脉粥样硬化的独立危险因素，但其确切机制仍不完全明了。前期研究发现较高浓度或较长时程的镉能够减弱人脐静脉内皮细胞（HUVECs）增殖、促进HUVECs凋亡，且ALDH2的活性受到明显的抑制，并具有浓度依赖性和时间依赖性，但ALDH2蛋白表达量不变，ALDH2 Ser位点磷酸化水平增加；而JNK抑制剂能使ALDH2活性恢复，Ser位点磷酸化水平降低。因此提出假说：镉激活JNK后磷酸化ALDH2某个特定的Ser/Thr位点从而抑制ALDH2的活性，导致有害醛类聚积和炎症反应，促进内皮细胞凋亡，导致动脉粥样硬化斑块不稳定。本研究拟在已有工作基础上，从细胞、动物等水平验证JNK-ALDH2在镉促进内皮细胞凋亡及动脉粥样硬化斑块易损性中的作用及机制，为动脉粥样硬化的防治提供分子生物学依据。

The mechanisms of the initiation and progression of atherosclerosis are complicated and not yet well understood. More and more researches indicated that cadmium is an independent risk factor of atherosclerosis, and could affect the initiation and progression of atherosclerosis, but the precise mechanisms are still not fully understood. In our preliminary experiments, we found that cadmium with a higher concentration or a longer exposure time could decrease the proliferation of human umbilical vein endothelial cells and promote their apoptosis; and activity of ALDH2 was obviously inhibited in a dose- and time-dependent manner with an increased phosphorylation level of some Ser residues, but there were no changes of ALDH2 protein expression. Moreover, JNK inhibitor could restore the activity of ALDH2 and lead to a decrease of phosphorylation level of these Ser residues. Therefore, we put forward the hypothesis: cadmium can inhibit the activity of ALDH2 through activating JNK, subsequently phosphorylating a specific ALDH2 Ser/Thr residue, which leads to the accumulation of harmful aldehydes and inflammation, endothelial cell apoptosis and atherosclerotic plaque instability. The study aims at investigating the effect and underlying mechanisms of JNK-ALDH2 on the cadmium-induced endothelial cell apoptosis and atherosclerotic plaque vulnerability from levels of cells and animal models, in order to provide the basis for prevention and therapy of atherosclerosis.