摘要：
Oxidized low-density lipoprotein (ox-LDL) is an independent risk factor of atherosclerosis. However, the mechanism underlying its pro-atherosclerosis roles has not yet been well explored. DNA demethylation modification, via DNA methyltransferases or ten-eleven-translocation (TET) family, is a crisis epigenetic regulation for various biological and pathological processes. This study aimed to investigate the effects of ox-LDL on macrophage autophagy and its potential epigenetic mechanism. Results showed that after treatment with 0, 10, 20, 40 or 80 mg/L ox-LDL for 24 h, the autophagy markers Beclin 1 and LC3 expression were obviously decreased at protein levels (P < 0.05). The mRNA and protein expression of TET2 was evidently decreased (P < 0.05). After pre-treatment with TET2 siRNA, the mRNA and protein levels of Beclin 1 and LC3 decreased compared with the 80 mg/L treatment group (P < 0.01). The mRNA and protein levels of Beclin 1 and LC3-II were up-regulated (P < 0.05) in the 5-aza-2′-deoxycytidine (a DNA methyltransferase inhibitor) of pretreatment group. Consistent with the Western blot results, cell immunofluorescence showed that the protein concentration of LC3-II decreased in the TET2 siRNA group and increased in the 5-aza-2′-deoxycytidine group. Taken together, these results showed that DNA demethylation modifications regulate ox-LDL-treated THP-1 macrophages autophagy and TET2 might be a novel regulator.
摘要：
Aim To compare the functional difference of endothelial progenitor cells(EPC) of high concentration Lp( a)( ≥300 mg / L) coronary artery disease( HLPCAD) patients and low concentration Lp( a)( < 300 mg / L) coronary artery disease( LLPCAD) patients. Methods Differential adherence method was used to isolate EPC,Dil-acLDL swallowed and lectin binding was used for EPC identification. MTT was used to assay EPC survival and proliferation,modified Boyden chamber for migration,gelatin slide method for adhesion,a single cell hybridoma clones dish was observed and counted,and tubular structures formed on matrigel matrix length was measured. Results The numbers of circulating EPC in HLPCAD patients were significantly lower than those in LLPCAD patients( 109. 4 ± 13. 8 Cells / field vs. 384. 0 ± 37. 0 Cells / field,P = 0. 0023). MTT analysis showed that the OD value of LLPCAD group was 0. 77 ± 0. 05,and the HLPCAD was 0. 23 ± 0. 04( P = 0. 0018),the apoptosis rate of HLPCAD EPC was significantly higher than that in LLPCAD group(14. 9% ± 3. 3% vs. 4. 1% ± 0. 8%,P = 0. 035). The numbers of adhesion(25. 3 ± 4. 6 Cells / field vs.78. 6 ± 6. 8 Cells / field,P = 0. 0030),migration(22. 0 ± 2. 6 Cells / field vs. 56. 0 ± 4. 9 Cells / field,P = 0. 0037),and clone-form units(2. 4 ± 0. 4 number / field vs. 11. 0 ± 1. 3 number / field,P = 0. 0003),tubular structure formation(7. 4 ±1. 2 mm / field vs. 33. 3 ± 2. 6 mm / field,P = 0. 0001) of HLPCAD patients were significantly reduced. Conclusions Function of HLPCAD EPC is seriously impaired while compared with LLPCAD EPC.内皮祖细胞(endothelial progenitor cell,EPC)是
作者机构：
[Wu, Minghua; Lei, Qianqian; Wang, Zeyou; Wang, Wei; Yu, Zhibin; Li, Guiyuan; Xu, Gang; Liu, Xiaoping] Cent S Univ, Hunan Prov Tumor Hosp, Changsha 410013, Hunan, Peoples R China.;[Wu, Minghua; Lei, Qianqian; Wang, Zeyou; Wang, Wei; Yu, Zhibin; Li, Guiyuan; Xu, Gang; Liu, Xiaoping] Cent S Univ, Xiangya Med Sch, Affiliated Tumor Hosp, Changsha 410013, Hunan, Peoples R China.;[Tang, Hailin; Liu, Xiaoping] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Dept Breast Oncol,Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China.;[Wu, Minghua; Li, Guiyuan] Cent S Univ, Key Lab Carcinogenesis & Canc Invas, Key Lab Carcinogenesis, Sch Basic Med Sci,Canc Res Inst,Minist Educ,Minis, Changsha 410078, Hunan, Peoples R China.;[Xu, Gang] Univ South China, Coll Med, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Wu, Minghua] C;Cent S Univ, Key Lab Carcinogenesis & Canc Invas, Key Lab Carcinogenesis, Sch Basic Med Sci,Canc Res Inst,Minist Educ,Minis, Changsha 410078, Hunan, Peoples R China.
关键词：
LIM-only protein 3;apoptosis;epigenetics;miR-101;polycomb repressive complex 2
摘要：
LIM-only protein 3 (LMO3), a member of the LIM-only protein group, is a new DNA methylation gene that was identified in gliomas via the MeDIP-Chip in our previous study. In this study, we found that LIM-only protein 3 (LMO3) is hypomethylated and overexpressed in glioma cells and tissues. The overexpression of LMO3 was correlated with a poor prognosis in glioma patients, and LMO3 was indirectly inhibited by the tumor suppressor miR-101, which is a potential prognosis marker of gliomas. MiR-101 decreased the expression of LMO3 by reversing the methylation status of the LMO3 promoter and by inhibiting the presence of the methylation-related histones H3K4me2 and H3K27me3 and increasing the presence of H3K9me3 and H4K20me3 on the promoter. It was determined that miR-101 decreases the occupancy of H3K27me3 by inhibiting EZH2, DNMT3A and EED and decreases the H3K9me3 occupancy on the LMO3 promoter via SUV39H1, SUV39H2, G9a and PHF8. Furthermore, miR-101 suppresses the expression of LMO3 by decreasing USF and MZF1.
摘要：
Lipoprotein(a) [Lp(a)] is a highly atherogenic lipoprotein, whose metabolism is poorly understood. Efficient and secure drugs that can lower elevated plasma Lp(a) concentrations are currently lacking. Fibroblast growth factor-21 (FGF-21), a member of the FGFS super family, regulates glucose and lipid metabolism in hepatocytes and adipocytes via FGFR-ERK1/2 signaling. In this study, we investigated the molecular mechanisms that influence apolipoprotein(a) [apo(a)] biosynthesis. We also determined the effects of FGF21 on HepG2 cell apo(a) expression and secretion, as well as the mechanism of FGF21 in these effects. Results showed that FGF21 inhibited apo(a) expression at both mRNA and protein levels in a dose- and time--dependent manner and then suppressed the secretion of apo(a). These effects were attenuated by PD98059 (ERK1/2 inhibitor) and Elk-1 siRNA. PD166866 (FGFR1 inhibitor) also attenuated the FGF21-mediated inhibition of apo(a) expression and inhibited ERK1/2 and Elk-1 activation. These results demonstrate that FGF21 suppresses apo(a) expression via the FGFR1-ERK1/2-Elk-1 pathway.
作者机构：
[GUO Feng-xia; LI Xiao-hong; PENG Juan; TANG Ya-ling; YANG Qin; LIU Lu-shan; WANG Zuo; JIANG Zhi-sheng; WEI Dang-heng] Institute of Cardiovascular disease,Key Laboratory for Arteriosclerology of Hunan Province,University of South China,Hengyang 421001,China
摘要：
Melatonin is biosynthesized in the pineal gland and secreted into the bloodstream. Evidences indicate a role of melatonin in the regulation of glucose metabolism. The objective of this study was to investigate the effect of melatonin on insulin sensitivity in insulin resistant adipocytes. Following a preincubation with melatonin or vehicle for 30 min, insulin resistant cells of 3T3-L1 adipocytes were induced by palmitic acids (300 mu M, 6 h). Our results showed that palmitic acids inhibited both the basal and insulin-stimulated uptake of [H-3]-2-Deoxyglucose, down-regulated the levels of IRS-1 and GLUT-4. However, compared to the vehicle group, melatonin pre-treatment increased significantly the uptake of [H-3]-2-Deoxyglucose as well as the level of GLUT-4, and decreased phosphorylated IRS-1 (Ser307) although total IRS-1 did not change significantly. These data suggest that palmitic acids impair insulin signal via down-regulating the expressions of IRS-1 and GLUT-4; whereas melatonin can ameliorate insulin sensitivity by inhibiting Ser307 phosphorylation in IRS-1 and increasing GLUT-4 expressions in insulin resistant 3T3-L1 adipocytes. We conclude that melatonin regulates the insulin sensitivity and glucose homeostasis via inhibiting Ser-phosphorylation and improving function of IRS-1. (C) 2014 Elsevier Masson SAS. All rights reserved.
通讯机构：
[Wei, Dangheng] U;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.
作者机构：
[唐伟军; 李雪飞; 谭玉林] Dept. of Pathophysiology, Xiangnan University, Chenzhou, Hunan 423000, China;[王佐; 刘录山; 姜志胜; 任重; 唐志晗] Institute of Cardiovascular Disease, University of South China, Hengyang, Hunan 421001, China;[邓华菲] Dept. of Pathophysiology, Xiangnan University, Chenzhou, Hunan 423000, China, Institute of Cardiovascular Disease, University of South China, Hengyang, Hunan 421001, China
