Tian Xin, Shi Yongfeng, Liu Ning, Yan Youyou, Li Tianyi, Hua Peiyan, Liu Bin
Department of Cardiology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Mol Med Rep. 2016 Nov;14(5):4173-4179. doi: 10.3892/mmr.2016.5733. Epub 2016 Sep 12.
Hyperhomocysteinemia is characterized by an abnormally high level of homocysteine (Hcy) in the blood and is associated with cardiovascular diseases such as atherosclerosis. Endothelial dysfunction may lead to the pro-atherogenic effects associated with hyperhomocysteinemia. Endothelial dysfunction induced by Hcy has been previously investigated; however, the underlying molecular mechanism remains to be fully elucidated. The present study investigated whether death-associated protein kinase (DAPK) is involved in Hcy‑induced apoptosis in human umbilical vein endothelial cells (HUVECs). It was determined that Hcy treatment upregulated the mRNA and protein expression levels of DAPK in HUVECs. Additionally, it was identified that the knockdown of DAPK using small interfering RNA may attenuate the Hcy-induced apoptosis and dissipation of mitochondrial membrane potential. DAPK inhibition may also reverse the effect of Hcy by the upregulation of B cell leukemia/lymphoma 2 (Bcl2) and poly ADP‑ribose polymerase, and the downregulation of Bcl2‑associated X protein (Bax) and of caspase 3. In conclusion, the present study demonstrated that DAPK contributed to the Hcy‑induced endothelial apoptosis via modulation of Bcl2/Bax expression levels and activation of caspase 3.
高同型半胱氨酸血症的特征是血液中同型半胱氨酸（Hcy）水平异常升高，并与动脉粥样硬化等心血管疾病相关。内皮功能障碍可能导致与高同型半胱氨酸血症相关的促动脉粥样硬化作用。此前已对Hcy诱导的内皮功能障碍进行了研究；然而，其潜在的分子机制仍有待充分阐明。本研究调查了死亡相关蛋白激酶（DAPK）是否参与Hcy诱导的人脐静脉内皮细胞（HUVECs）凋亡。结果确定，Hcy处理上调了HUVECs中DAPK的mRNA和蛋白表达水平。此外，还发现使用小干扰RNA敲低DAPK可减弱Hcy诱导的凋亡以及线粒体膜电位的消散。DAPK抑制还可能通过上调B细胞白血病/淋巴瘤2（Bcl2）和聚ADP核糖聚合酶，并下调Bcl2相关X蛋白（Bax）和半胱天冬酶3来逆转Hcy的作用。总之，本研究表明，DAPK通过调节Bcl2/Bax表达水平和激活半胱天冬酶3，促进了Hcy诱导的内皮细胞凋亡。
