作者机构：
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China;Department of Pathology, Affiliated Hui Zhou Hospital (The Third People's Hospital of Huizhou), Guangzhou Medical University, Huizhou, Guangdong Province 516002, PR China;The Second Hospital Affiliated to University of South China, Hengyang, Hunan 421001, PR China
通讯机构：
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, China
通讯机构：
[Wei, Dangheng] Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 42001, Peoples R China.
摘要：
Atherosclerosis initiates at predictable focal sites near arterial branches and curves, where blood flow is disturbed and shear stress is complex. Endothelial shear stress is the tangential stress derived from the friction of the flowing blood on the endothelial surface of the arterial wall. It is a key factor in modulating endothelial cell gene expression and vascular development and remodeling. Increasing evidences suggest that shear stress patterns have a strong relationship with atherosclerotic features. Moreover, variations in the local artery geometry during atherogenesis further modify flow shear stress characteristics, which contribute to the rupture site at the plaque upstream. In this study, we summarize the mechanistic evidences that associate shear stress patterns with determined atherosclerotic plaque features. An enhanced understanding of the relationship and pathophysiological function of shear stress patterns in atherosclerotic plaque features is essential, which may provide early prediction of clinical risk and guide individualized treatment strategies. In the current review, we analyzed the function of shear stress on the determination of atherosclerotic lesion and provided an update on the mechanotransduction of shear stress, gene expression regulation, and atherosclerotic plaque development and rupture.
期刊：
DNA and cell biology,2019年38(7):597-606 ISSN：1044-5498
通讯作者：
Li, GH;Wei, DH
作者机构：
[Chen, Jinna; Li, Guohua; Peng, Wenxi; Wu, Peng; Wang, Zuo; Wei, Dangheng] 1 Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, P.R. China;[Cai, Guoding] 2 Department of Cardiothoracic Surgery, The First Affiliated Hospital of University of South China;[Xia, Yiping] 3 University of South China of Nursing, Hengyang, P.R. China
通讯机构：
Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, China
期刊：
DNA and Cell Biology.,2018年37(6):517-523 ISSN：1044-5498
通讯作者：
Wang, Zuo
作者机构：
[Chen, Jiaojiao; Liu, Yami; Zeng, Zhaolin; Wang, Zuo; Wei, Dangheng] Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Peng, Wen] Univ South China, Affiliated Hosp 1, Dept Spine Surg, Hengyang, Hunan, Peoples R China.;[Qu, Kai] Chongqing Univ, Coll Bioengn, Chongqing, Peoples R China.;[Lin, Xiaolong] Third Peoples Hosp Huizhou, Dept Pathol, Huizhou, Peoples R China.
通讯机构：
[Wang, Zuo] Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
关键词：
DNA demethylation;TET2;atherosclerosis;inflammation
摘要：
Atherosclerosis is the underlying cause of cardio-cerebrovascular disease. However, the mechanisms of atherosclerosis are still unclear. The modification of DNA methylation has an important role in atherosclerosis development. As a member of the Ten-eleven translocation (TET) family, TET methylcytosine dioxygenase 2 (TET2) can modify DNA methylation by catalyzing 5-methylcytosine to 5-hydroxymethylcytosine and mediate DNA demethylation. Recent findings suggest that TET2 is related to the phenotype transformation of vascular smooth muscle cells, endothelial dysfunction, and inflammation of macrophage, the key factors of atherosclerosis. Therefore, TET2 may be a potential target for atherosclerosis treatment. This review will elaborate the recent findings that suggest the role of TET2 in atherosclerosis.
期刊：
Annals of Biomedical Engineering,2016年44(7):2218-2227 ISSN：0090-6964
通讯作者：
Wei, Dangheng;Peng, Zhao;Wang, Yu
作者机构：
[Li, Xiaohong; Yang, Qin; Li, Rongqing; Jiang, Zhisheng; Peng, Juan; Wang, Zuo; Wei, Dangheng] Univ South China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.;[Peng, Zhao] Xiang Nan Univ, Affiliated Hosp, Chengzhou 423000, Peoples R China.;[Wang, Yu] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Neurosurg, Wuhan 430030, Peoples R China.;[Tang, Xiaoqing] Univ South China, Sch Med, Dept Physiol, Hengyang 421001, Peoples R China.;[Tang, Xiaoqing] Univ South China, Sch Med, Inst Neurosci, Hengyang 421001, Peoples R China.
通讯机构：
[Wei, Dangheng] Univ South China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.;[Peng, Zhao] Xiang Nan Univ, Affiliated Hosp, Chengzhou 423000, Peoples R China.;[Wang, Yu] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Neurosurg, Wuhan 430030, Peoples R China.
关键词：
*Atherosclerosis;*Autophagy;*Endothelial cell;*Low shear stress;*Ten-eleven translocation 2 protein
摘要：
Low shear stress plays a crucial role in the initiation and progression of atherosclerotic lesions. However, the detailed mechanisms of these processes remain unclear. In this study, the effect of low shear stress on endothelial cell autophagy and its potential mechanism were investigated. Results showed autophagy dysfunction and ten-eleven translocation 2 (TET2) protein downregulation during atherosclerotic lesion progression. Autophagic markers BECLIN 1 and LC3II/LC3I under low shear stress (5 dyne/cm(2)) obviously decreased compared with those under physiological shear stress (15 dyne/cm(2)), whereas autophagic substrate p62 increased. TET2 expression was also downregulated under low shear stress. Endothelial cell autophagy was improved with TET2 overexpression but was impaired by TET2 siRNA treatment. Moreover, TET2 overexpression upregulated the expression of endothelial cell nitric oxide synthase (eNOS) and downregulated the expression of endothelin-1 (ET-1). TET2 siRNA further attenuated eNOS expression and stimulated ET-1 expression. Overall, the results showed that low shear stress downregulated endothelial cell autophagy by impaired TET2 expression, which might contribute to the atherogenic process.
作者机构：
The Institute of Cardiovascular Disease, University of South China, Heng Yang 421001, P.R.China;Bioengineering College of Chongqing University and Key Lab for Biomedical Engineering of Chongqing, Chongqing 400044, P.R.China
摘要：
Oxidised lipoprotein(a) [oxLp(a)] is considered as a more potent arteriosclerotic factor than native Lp(a). However, the molecular mechanisms underlying this potency remain unclear. Reactive oxygen species (ROS) possibly act as intracellular second messengers that participate in autophagy stimulation. In this study, the effect of oxLp(a) on endothelial cell autophagy was determined. The mechanism and effect of autophagy on endothelial cells were also investigated. Results showed that oxLp(a) could induce autophagy depending on the generation of cellular ROS. Superoxide dismutase, an antioxidant, could inhibit oxLp(a)-induced autophagy in human umbilical vascular endothelial cells. Furthermore, poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1)-liver kinase B1 (LKB1)-adenosine monophosphate-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) and LKB1-AMPK-mTOR pathways are involved in oxLp(a)-induced autophagy. These pathways are also dependent on ROS. Thus, oxLp(a) induced autophagy via LKB1-AMPK-mTOR and PAPR-1-LKB1-AMPK-mTOR pathways, which are dependent on ROS generation. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
