期刊：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2016年472(3):410-417 ISSN：0006-291X
通讯作者：
Tang, CK
作者机构：
[Gong, Duo; Tan, Yu-Lin; Cheng, Hai-Peng; Li, Liang; Xie, Wei; Lan, Gang; Huang, Chong; Zhang, Min; Liu, Dan] Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China;[Tang, Chao-Ke] Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China. Electronic address: tangchaoke@qq.com;[Zheng, Xi-Long] Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta, T2N 4N1, Canada;[Yin, Wei-Dong] Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China. Electronic address: yysweets@126.com
通讯机构：
[Yin, Wei-Dong; Tang, Chao-Ke] Univ South China, Inst Cardiovasc Res, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
摘要：
Angiopoietin-like 4 (Angptl4), a secreted protein, is an important regulator to irreversibly inhibit lipoprotein lipase (LPL) activity. Macrophage LPL contributes to foam cell formation via a so-called"molecular bridge" between lipoproteins and receptors on cell surface. It has been reported that macrophage ANGPTL4 suppresses LPL activity, foam cell formation and inflammatory gene expression to reduce atherosclerosis development. Recently, some studies demonstrated that microRNA-134 is upregulated in atherosclerotic macrophages. Here we demonstrate that miR-134 directly binds to 3'UTR of ANGPTL4 mRNA to suppression the expression of ANGPTL4. To investigate the potential roles of macrophage miR-134, THP-1 macrophages were transfected with miR-134 mimics or inhibitors. Our results showed that LPL activity and protein were dramatically increased. We also found that miR-134 activated LPL-mediated lipid accumulation. Collectively, our findings indicate that miR-134 may regulate lipid accumulation and proinfiammatory cytokine secretion in macrophages by targeting the ANGPTL4 gene. Our results have also suggested a promising and potential therapeutic target for atherosclerosis. (C) 2016 Elsevier Inc. All rights reserved.
期刊：
Life Science Research,2003年7(2):95-103 ISSN：1007-7847
作者机构：
[Kazuhiko Tsutsumi] Research and Development,Otsuka Pharmaceutical Factory, Inc., Naruto,Tokushima;[Yin Weidong] Department of Biochem & Molecular Biology,Nanhua University School of Life Sciences and Technology;[Yuan Zhonghua] Institute of Cardiovascular Research.Nanhua University Medical School
关键词：
lipoprotein lipase;NO-1886;atherosclerosis
摘要：
Lipoprotein lipase (LPL) is a key enzyme in regulation of lipoprotein metabolism, especially in breaking down plasma triglycerides (TG) of TG-rich lipoproteins, including chylomicrons and very low density lipoproteins (VLDL) .Dysfunction of LPL contributes to hypertriglyceridemia and decreased high density lipoprotein cholesterol level, which in turn increases risk of atherosclerosis. Ppromoting LPL activity inhibit atherosclerosis was once proposed and a LPL activator to validate our hypothesis was synthesized. The completed studies have shown that NO-1886 increased LPL mRNA and LPL activity in adipose tissue, myocardium and skeletal muscle, resulting in an elevation of postheparin plasma LPL activity and LPL mass, and also decreased plasma TG concentration with a concomitant rise in plasma HDL-C,inhibited the development of atherosclerosis.
作者机构：
[Lan, Gan; He, Ping-Ping; Shi, Jin-Feng; Peng, Juan; Zhang, Min; Li, Yuan; Lv, Yun-Cheng; Xie, Wei; Tang, Yan-Yan; Zhang, Chi] Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China;[Liu, Xiang-Yu] Department of Biochemistry and Molecular Biology, School of Life Sciences and Technology, University of South, Hengyang, Hunan 421001, China;[He, Ping-Ping] School of Nursing, University of South China, Hengyang, Hunan 421001, China;[Zheng, Xi-Long] Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, The University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada;[Peng, Juan] Yongzhou Vocational and Technical College, Yongzhou, Hunan 425000, China
通讯机构：
[Yin, Wei-Dong] Univ South China, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.
摘要：
Background: Atherosclerosis is a major cause of coronary artery disease, which is characterized by cellular lipid accumulation. Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism. Studies have shown that macrophage-derived LPL exhibits proatherogenic properties, and plays a major role in lipid accumulation in macrophages. Evidence suggests that oxidative stress can effectively enhance macrophage LPL production. Betulinic acid (BA) is a pentacyclic lupane triterpene with a potent antioxidant activity. In this study, we investigated whether BA affects the expression of macrophage LPL and how it regulates cellular lipid accumulation. Methods and results: We revealed that BA downregulated H2O2-simulated macrophage LPL protein, mRNA levels and its activity in both concentration- and time-dependent manners. Furthermore, BA decreased LPL-involved total cholesterol and triglyceride levels in macrophages. In addition, cellular lipid staining by Oil Red 0 showed that BA decreased cellular lipid droplet deposition. Next, we confirmed that pretreatment with BA decreased H2O2-induced production of intracellular reactive oxygen species in a concentration-dependent manner. Further studies demonstrated that BA inhibited H2O2-induced membrane translocation of PKC, phosphorylation of ERK1/2 and c-Fos. Finally, the induction of LPL production and activity by H2O2 was abolished by BA, inhibition of PKC or ERK or depletion c-Fos, respectively. Conclusions: BA, through its role of antioxidant activity, attenuated macrophage-derived LPL expression and activity induced by oxidative stress, and effectively reduced cellular lipid accumulation, likely through inhibition of the pathways involving PKC, ERK and c-Fos. These effects of BA may contribute to its mitigation of atherosclerosis and help develop BA as a therapeutic compound in treatment of atherosclerosis. (C) 2015 Published by Elsevier B.V.
作者机构：
[Gong, Duo; OuYang, Xin-Ping; Cheng, Hai-Peng; He, Ping-Ping; Lan, Gang; Zhang, Min; Liu, Dan; Li, Yuan; Lv, Yun-Cheng; Tang, Chao-Ke; Tan, Yu-Lin; Li, Liang; Yin, Wei-Dong; Xie, Wei; Yao, Feng; Huang, Chong] Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China;[OuYang, Xin-Ping; He, Ping-Ping; Tang, Chao-Ke; Wang, Zong-Bao; Yin, Wei-Dong] Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, 28 West Changsheng Road, Hengyang 421001, Hunan, China;[OuYang, Xin-Ping] Department of Physiology, The Neuroscience Institute, Medical College, University of South China,Hengyang, Hunan, 421001, China;[He, Ping-Ping; Li, Zhao-Xia] Nursing School, University of South China, Hengyang 421001, Hunan, China;[Zheng, Xi-Long] Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta, Canada
通讯机构：
[Yin, Wei-Dong] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.
摘要：
Recent studies have suggested that miR-590 may play critical roles in cardiovascular disease. This study was designed to determine the effects of miR-590 on lipoprotein lipase (LPL) expression and development of atherosclerosis in apolipoprotein E knockout (apoE(-/-)) mice and explore the potential mechanisms. En face analysis of the whole aorta revealed that miR-590 significantly decreased aortic atherosclerotic plaque size and lipid content in apoE (-/-) mice. Double immunofluorescence staining in cross-sections of the proximal aorta showed that miR-590 agomir reduced CD68 and LPL expression in macrophages in atherosclerotic lesions. MiR-590 agomir down-regulated LPL mRNA and protein expression as analyzed by RT-qPCR and western blotting analyses, respectively. Consistently, miR-590 decreased the expression of CD36 and scavenger receptor A1 (SRA1) mRNA and protein. High-performance liquid chromatography (HPLC) analysis confirmed that treatment with miR-590 agomir reduced lipid levels either in plasma orinabdominal cavity macrophages of apoE(-/-) mice. ELISA analysis showed that miR-590 agomir decreased plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6). In contrast, treatment with miR-590 antagomir prevented or reversed these effects. Taken together, these results reveal a novel mechanism of miR-590 effects, and may provide new insights into the development of strategies for attenuating lipid accumulation and pro-inflammatory cytokine secretion.
期刊：
Clinica chimica acta; international journal of clinical chemistry,2016年453:107-113 ISSN：0009-8981
通讯作者：
Yin, Wei-Dong;Tang, Chao-Ke
作者机构：
[Tang, Chao-Ke] Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China. Electronic address: tangchaoke@qq.com;[Li, Liang; Xie, Wei] Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China;[Li, Liang] Department of Pathophysiology, University of South China, Hengyang 421001, Hunan, China;[Zheng, Xi-Long] Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada;[Yin, Wei-Dong] Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China. Electronic address: wdy20042004@126.com
通讯机构：
[Yin, Wei-Dong; Tang, Chao-Ke] Univ South China, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.
摘要：
Cardiovascular diseases, such as atherosclerosis and hypertension, are the major cause of mortality and morbidity in the world. Adropin was first discovered in 2008 by Kumar and his coworkers. Adropin, encoded by the Energy Homeostasis Associated gene, is expressed in many tissues and organs, such as pancreatic tissue, liver, brain, kidney, endocardium, myocardium, and epicardium. In this review, we have summarized recent data suggesting the roles of adropin in several major cardiovascular diseases. Increasing evidence suggests that adropin is a potential regulator of cardiovascular functions and plays a protective role in the pathogenesis and development of cardiovascular diseases. However, further studies are needed to elucidate the specific mechanisms underlying the association between adropin and cardiovascular diseases. (C) 2015 Elsevier B.V. All rights reserved.
