Nε-Carboxymethyl-Lysine Deteriorates Vascular Calcification in Diabetic Atherosclerosis Induced by Vascular Smooth Muscle Cell-Derived Foam Cells
Nε-Carboxymethyl-Lysine Deteriorates Vascular Calcification in Diabetic Atherosclerosis Induced by Vascular Smooth Muscle Cell-Derived Foam Cells
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Nε-羧甲基-赖氨酸会恶化血管平滑肌细胞衍生的泡沫细胞诱导的糖尿病动脉粥样硬化的血管钙化
DOI：
10.3389/fphar.2020.00626
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发表时间：
2020-05-15
影响因子：
5.6
通讯作者：
Cao, Hui-Ling
中科院分区：
文献类型：
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作者：
Xu, Sui-Ning;Zhou, Xin;Cao, Hui-Ling
N ε-羧甲基赖氨酸（CML）是一种晚期糖基化终产物，参与糖尿病动脉粥样硬化血管钙化（VC）。本研究旨在探讨慢性粒细胞白血病（CML）对血管平滑肌细胞（VSMC）源性泡沫细胞诱导的糖尿病动脉粥样硬化中VC的影响。进行了人体研究、动物研究和细胞研究。来自100名患者的人体研究结果显示，患有冠状动脉疾病和糖尿病的患者血糖和血脂状态较差，冠状动脉病变和狭窄更严重。采用链脲佐菌素腹腔注射联合高脂饮食建立ApoE（-/-）小鼠糖尿病动脉粥样硬化模型。动物实验结果表明，CML通过加速ApoE（-/-）小鼠中VSMC衍生的泡沫细胞的积累，加速糖尿病动脉粥样硬化中VC的进展。细胞学研究结果表明，CML可诱导VSMC源性泡沫细胞凋亡，并加重泡沫细胞钙化。与这一发现相一致，钙含量和碱性磷酸酶，骨形态发生蛋白2和runt相关转录因子2的表达水平显着升高，在A7 r5细胞与氧化低密度脂蛋白和CML治疗。因此，我们得出结论，CML促进VSMC源性泡沫细胞钙化，加重糖尿病动脉粥样硬化中的VC，为泡沫细胞在糖尿病VC中的作用提供证据。
N epsilon-carboxymethyl-lysine (CML), an advanced glycation end product, is involved in vascular calcification (VC) in diabetic atherosclerosis. This study aimed to investigate the effects of CML on VC in diabetic atherosclerosis induced by vascular smooth muscle cell (VSMC)-derived foam cells. Human studies, animal studies and cell studies were performed. The human study results from 100 patients revealed a poor blood glucose and lipid status and more severe coronary lesions and stenosis in patients with coronary artery disease and diabetes mellitus. Intraperitoneal injection of streptozotocin combined with a high-fat diet was used to build a diabetic atherosclerosis model in ApoE(-/-)mice. The animal study results indicated that CML accelerated VC progression in diabetic atherosclerosis by accelerating the accumulation of VSMC-derived foam cells in ApoE(-/-)mice. The cell study results illustrated that CML induced VSMC-derived foam cells apoptosis and aggravated foam cells calcification. Consistent with this finding, calcium content and the expression levels of alkaline phosphatase, bone morphogenetic protein 2 and runt-related transcription factor 2 were significantly elevated in A7r5 cells treated with oxidation-low-density lipoprotein and CML. Thus, we concluded that CML promoted VSMC-derived foam cells calcification to aggravate VC in diabetic atherosclerosis, providing evidence for the contribution of foam cells to diabetic VC.