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
| Autor: | Linli Wang, Jingbo Chen, Zhengyu Zhang, Kefeng Liu, Suning Ping, Lie Deng, Adham Sa Bardeesi, Hong Wang, Yuhuang Li, Puyi Sheng, Dadi Chen, Ziqing Li, Jingjing Wang, Chaohong Li, Yuhuan Zhou, Shuying Liu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Glycation End Products Advanced Male Cancer Research Vascular smooth muscle Glycosylation Cell Apoptosis 030204 cardiovascular system & hematology Muscle Smooth Vascular chemistry.chemical_compound 0302 clinical medicine Myocyte Enzyme Inhibitors RNA Small Interfering Protein disulfide-isomerase Cell biology Up-Regulation medicine.anatomical_structure cardiovascular system NADPH Oxidase 1 Advanced glycation end-product Original Article Signal Transduction inorganic chemicals Immunology Myocytes Smooth Muscle Protein Disulfide-Isomerases Biology Diabetes Mellitus Experimental Veins 03 medical and health sciences Cellular and Molecular Neuroscience Downregulation and upregulation Blood vessel prosthesis medicine Animals Cell Proliferation Cell Biology Atherosclerosis nervous system diseases Blood Vessel Prosthesis body regions Mice Inbred C57BL 030104 developmental biology chemistry Stress Mechanical Reactive Oxygen Species |
| Zdroj: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|