Protein disulfide isomerase-mediated apoptosis and proliferation of vascular smooth muscle cells induced by mechanical stress and advanced glycosylation end products result in diabetic mouse vein graft atherosclerosis.
Protein disulfide isomerase-mediated apoptosis and proliferation of vascular smooth muscle cells induced by mechanical stress and advanced glycosylation end products result in diabetic mouse vein graft atherosclerosis.
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机械应力和高级糖基化终产物诱导的蛋白质二硫键异构酶介导的血管平滑肌细胞凋亡和增殖导致糖尿病小鼠静脉移植物动脉粥样硬化
DOI：
10.1038/cddis.2017.213
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发表时间：
2017-05-25
影响因子：
9
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Ping S;Liu S;Zhou Y;Li Z;Li Y;Liu K;Bardeesi AS;Wang L;Chen J;Deng L;Wang J;Wang H;Chen D;Zhang Z;Sheng P;Li C
蛋白质二硫键异构酶（PDI）涉及细胞存活和死亡。PDI是否介导机械牵张应力（SS）和/或晚期糖基化终产物（AGEs）触发的血管平滑肌细胞（VSMC）增殖和凋亡的同时增加尚不清楚。在这里，我们假设，不同的表达水平的PDI触发完全相反的细胞命运之间的不同VSMC亚型。将小鼠静脉移植到非糖尿病和糖尿病小鼠的颈动脉中8周;移植的静脉同时经历增殖和凋亡的增加，这引发了非糖尿病小鼠的静脉移植动脉化或糖尿病小鼠的动脉粥样硬化。糖尿病组细胞增殖和凋亡率明显高于对照组。SS和/或AGEs刺激静止培养的VSMCs，导致增殖和凋亡的同时增加，它们可以诱导增加的PDI激活和表达。在体内外实验中，增殖期VSMCs呈弱的PDI和SM-α-actin共表达，而凋亡或死亡细胞呈强的PDI和SM-α-actin共表达。SS或AGEs均可迅速上调PDI、NOX 1和ROS的表达，二者联合具有协同作用。抑制PDI可同时抑制VSMCs的增殖和凋亡，而细胞松弛素D抑制SM-α-actin可导致VSMCs凋亡增加，并切割caspase-3，但对增殖无影响。总之，不同表达水平的PDI在血管平滑肌细胞诱导SS和/或AGEs触发增殖和凋亡的同时增加，加速静脉移植动脉化或动脉粥样硬化，导致我们提出PDI作为一个新的目标，用于治疗血管重塑和疾病。
Protein disulfide isomerase (PDI) involves cell survival and death. Whether PDI mediates mechanical stretch stress (SS) and/or advanced glycosylation end products (AGEs)-triggered simultaneous increases in proliferation and apoptosis of vascular smooth muscle cells (VSMCs) is unknown. Here, we hypothesized that different expression levels of PDI trigger completely opposite cell fates among the different VSMC subtypes. Mouse veins were grafted into carotid arteries of non-diabetic and diabetic mice for 8 weeks; the grafted veins underwent simultaneous increases in proliferation and apoptosis, which triggered vein graft arterializations in non-diabetic or atherosclerosis in diabetic mice. A higher rate of proliferation and apoptosis was seen in the diabetic group. SS and/or AGEs stimulated the quiescent cultured VSMCs, resulting in simultaneous increases in proliferation and apoptosis; they could induce increased PDI activation and expression. Both in vivo and in vitro, the proliferating VSMCs indicated weak co-expression of PDI and SM-α-actin while apoptotic or dead cells showed strong co-expression of both. Either SS or AGEs rapidly upregulated the expression of PDI, NOX1 and ROS, and their combination had synergistic effects. Inhibiting PDI simultaneously suppressed the proliferation and apoptosis of VSMCs, while inhibition of SM-α-actin with cytochalasin D led to increased apoptosis and cleaved caspases-3 but had no effect on proliferation. In conclusion, different expression levels of PDI in VSMCs induced by SS and/or AGEs triggered a simultaneous increase in proliferation and apoptosis, accelerated vein graft arterializations or atherosclerosis, leading us to propose PDI as a novel target for the treatment of vascular remodeling and diseases.
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DOI：
10.1124/jpet.112.195446
发表时间：
2012-11-01
影响因子：
3.5
作者：
Cai, Yujun;Knight, Walter E.;Yan, Chen
通讯作者：
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DOI：
10.2478/ersc-2013-0001
发表时间：
2014-01
期刊：
Endoplasmic reticulum stress in diseases
影响因子：
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DOI：
10.1161/atvbaha.114.303410
发表时间：
2015-01
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
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作者：
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影响因子：
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作者：
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