作者机构：
[王程] Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, China;[王程] Department of Spine Surgery, the First Affiliated Hospital, University of South China, Hengyang 421001, China;[王文军; 晏怡果; 杨威] Department of Spine Surgery, the First Affiliated Hospital, University of South China, Hengyang 421001, China;[于小华] Life Science Research Center, University of South China, Hengyang 421001, China;[张健] Department of Hand and Micro-surgery, the First Affiliated Hospital, University of South China, Hengyang 421001, China
作者：
Cui Li-Bao;Yu Xiao-Hua;Jiang Chong-Hui;Tang Ya-Ling;Ouyang Xin-Ping;...
期刊：
生物化学与生物物理进展,2015年42(9):866-876 ISSN：1000-3282
通讯作者：
Tang Chao-Ke
作者机构：
[Ouyang Xin-Ping; Yao Feng; Yu Xiao-Hua; Cui Li-Bao; He Ping-Ping; Tang Chao-Ke; Lu Yun-Cheng; Zhang Min; Tang Ya-Ling] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res,Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Jiang Chong-Hui; Cui Li-Bao] Cent Hosp Hengyang, Dept Pharm, Hengyang 421001, Peoples R China.
通讯机构：
[Tang Chao-Ke] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res,Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
ABCA1;ABCG5;ABCG8;Atherosclerosis;HDL-C;Inflammation;Probucol;SR-B I
摘要：
Probucol is a potent hypolipidemic drug that decreases plasma high-density lipoprotein cholesterol (HDL-C) levels but attenuates atherosclerosis. However, the detailed mechanisms are not fully understood. The aim of this study was to explore the molecular mechanisms of the HDL-C-lowering and antiatherogenic effects of probucol. New Zealand white rabbits were randomly divided into normal diet group, normal diet+probucol group, high fat diet (HFD) group and HFD+probucol (HFD+P) group. After 7 weeks of treatments, the extent of the atherosclerotic lesions, hepatic lipid accumulation and plasma levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol and HDL-C were significantly reduced in HFD+P group as compared to HFD group. Probucol effectively inhibited down-regulation of hepatic scavenger receptor class B type I (SR-B I) expression, and ATP-binding cassette (ABC) transporters G5 (ABCG5) and G8 (ABCG8) expression in the liver and small intestine induced by HFD but further promoted HFD-induced reduction in hepatic ABC transporter A1 (ABCA1) expression. In addition, probucol also significantly prevented HFD-induced increases of tumor necrosis factor-alpha, interleukin-1, interleukin-6 and monocyte chemotactic protein-1 levels in the aortic arch and plasma. Thus, our data provide strong evidence that probucol alleviates atherosclerosis through regulating ABCA I, SR-B I, ABCG5 and ABCG8 expression and inhibiting the secretion of proinflammatory cytokines in hypercholesterolemic rabbits.
作者机构：
[刘理静; 张平] Dept. of Respiration, First Affiliated Hospital, China;[于小华] Life Science Research Center, University of South China, Hengyang, Hunan 421001, China
作者机构：
[Yu, Xiaohua; Zhao, Guojun; Yin, Kai; Li, Xiaoxu; Tang, Chaoke; Jiang, Zhisheng; Xiao, Ji; Mo, Zhongcheng] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Yu, Xiaohua] Univ S China, Sch Nursing, Hengyang 421001, Peoples R China.;[Fu, Yuchang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.;[Zha, Xiaohui] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada.
通讯机构：
[Tang, Chaoke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
Niemann–Pick type C1;oxLDL;ERK1/2;COX-2;PPARα;cholesterol
摘要：
The Niemann–Pick type C1 (NPC1) is located mainly in the membranes of the late endosome/lysosome and controls the intracellular cholesterol trafficking from the late endosome/lysosome to the plasma membrane. It has been reported that oxidized low-density lipoprotein (oxLDL) can up-regulate NPC1 expression. However, the detailed mechanisms are not fully understood. In this study, we investigated the effect of oxLDL stimulation on NPC1 expression in THP-1 macrophages. Our results showed that oxLDL up-regulated NPC1 expression at both mRNA and protein levels in a dose-dependent and time-dependent manner. In addition, oxLDL also induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Treatment with oxLDL significantly increased cyclooxygenase-2 (COX-2) mRNA and protein expression in the macrophages, and these increases were suppressed by the ERK1/2 inhibitor PD98059 or ERK1/2 small interfering RNA (siRNA) treatment. OxLDL up-regulated the expression of peroxisome proliferator-activated receptor α (PPARα) at the mRNA and protein levels, which could be abolished by COX-2 siRNA or COX-2 inhibitor NS398 treatment in these macrophages. OxLDL dramatically elevated cellular cholesterol efflux, which was abrogated by inhibiting ERK1/2 and/or COX-2. In addition, oxLDL-induced NPC1 expression and cellular cholesterol efflux were reversed by PPARα siRNA or GW6471, an antagonist of PPARα. Taken together, these results provide the evidence that oxLDL can up-regulate the expression of the NPC1 through ERK1/2/COX-2/PPARα-signaling pathway in macrophages.
摘要：
Background Macrophage migration inhibitory factor (MIF) is an upstream regulator in immune and inflammatory responses. However, its role in viral myocarditis remains unknown. In this study, we investigated the role of the MIF in coxsackievirus B3 (CVB3)-induced myocarditis. Methods Mice were randomized into two groups receiving either Eagle’s minimal essential medium (EMEM, control group) or virus solution (infected group). Subsets of mice in the infected group were sacrificed on days 3, 7, 14 and 28 after inoculation. Expression of MIF was detected using an enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction and immunohistochemistry. A neutralizing antibody (Ab) to MIF was injected intraperitoneally from day 0 to 7 after inoculation. Disease severity was estimated by histopathology of the heart and by the heart weight to body weight ratio, and the interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in the myocardium were measured by ELISA on day 14. Results The serum MIF concentration and expression levels of myocardial MIF mRNA and protein were significantly elevated in mice on days 7 and 14 post-infection. The survival rate was markedly higher and disease severity was obviously less in mice treated with anti-MIF Ab. Furthermore, MIF blockade significantly decreased the IL-1β and TNF-α in the myocarditic heart. Conclusion These results demonstrate that MIF is an important naturally occurring inflammatory cytokine in CVB3-induced myocarditis, and anti-MIF Ab may lessen the inflammatory response.
摘要：
Cholesterol efflux from lipid-loaded cells is a key athero-protective event that counteracts cholesterol uptake. The imbalance between cholesterol efflux and uptake determines the prevention or development of atherosclerosis. Many proteins and factors participate in the cholesterol efflux event. However, there are currently no systematic models of reverse cholesterol transport (RCT) that include most RCT-related factors and events. On the basis of recent research findings from other and our laboratories, we propose a novel model of one center and four systems with coupling transportation and networking regulation. This model represents a common way of cholesterol efflux; however, the systems in the model consist of different proteins/factors in different cells. In this review, we evaluate the novel model in vascular smooth muscle cells (VSMCs) and macrophages, which are the most important original cells of foam cells. This novel model consists of 1) a caveolae transport center, 2) an intracellular trafficking system of the caveolin-1 complex, 3) a transmembrane transport system of the ABC-A1 complex, 4) a transmembrane transport system of the SR-B1 complex, and 5) an extracelluar trafficking system of HDL/Apo-A1. In brief, the caveolin-1 system transports cholesterol from intracellular compartments to caveolae. Subsequently, both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to extracellular HDL/Apo-A1. The four systems are linked by a regulatory network. This model provides a simple and concise way to understand the dynamic process of atherosclerosis.
作者机构：
[He Ji-Shan; Xiong Ping; Guo Ping] Cent S Univ, Sch Infophys & Geomat Engn, Changsha 410083, Peoples R China.;[Li Xin-Xia; Guo Ping] Univ S China, Dept Nucl Phys, Hengyang 421001, Peoples R China.
通讯机构：
[Guo Ping] C;Cent S Univ, Sch Infophys & Geomat Engn, Changsha 410083, Peoples R China.
关键词：
field emission;molybdenum dioxide;enhancement factor
摘要：
The transport and capture of therapeutic magnetic nanoparticles in human microvasculature is studied numerically. The nanoparticles are injected into a vascular system upstream from malignant tissue, and are captured at the tumour site with the aid of a local applied magnetic field positioned outside the body. Taking into account the dominant magnetic and fluidic forces on the particles, our study shows that the nanoparticles can be directed to and concentrated at the desired zone that is within a few centimetres from the surface of the body. In addition, influence of the particles size, average blood flow velocity and the diameter of the blood vessel on the captured efficiency are parametrically analysed.
