摘要:
Reverse cholesterol transport (RCT) has been characterized as a crucial step for antiatherosclerosis, which is initiated by ATP-binding cassette A1 (ABCA1) to mediate the efflux of cellular phospholipids and cholesterol to lipid-free apolipoprotein A-I (apoA-I). However, the mechanisms underlying apoA-I/ABCA1 interaction to lead to the lipidation of apoA-I are poorly understood. There are several models proposed for the interaction of apoA-I with ABCA1 as well as the lipidation of apoA-I mediated by ABCA1. ApoA-I increases the levels of ABCA1 protein markedly. In turn, ABCA1 can stabilize apoA-I. The interaction of apoA-I with ABCA1 could activate signaling molecules that modulate posttranslational ABCA1 activity or lipid transport activity. The key signaling molecules in these processes include protein kinase A (PKA), protein kinase C (PKC), Janus kinase 2 (JAK2), Rho GTPases and Ca2+, and many factors also could influence the interaction of apoA-I with ABCA1. This review will summarize these mechanisms for the apoA-I interaction with ABCA1 as well as the signal transduction pathways involved in these processes.
摘要:
Atherosclerosis (As) is now widely appreciated to represent a chronic inflammatory reaction of the vascular wall in response to dyslipidemia and endothelial distress involving the inflammatory recruitment of leukocytes and the activation of resident vascular cells. MicroRNAs (miRNAs) are a group of endogenous, small (similar to 22 nucleotides in length) non-coding RNA molecules, which function specifically by base pairing with mRNA of genes, thereby induce translation repressions of the genes within metazoan cells. Recently, the function of miR-27, one of the miRNAs, in the initiation and progression of atherosclerosis has been identified. In vivo and in vitro studies suggest that miR-27 may serve as a diagnostic and prognostic marker for atherosclerosis. More recently, studies have identified important roles for miR-27 in angiogenesis, adipogenesis, inflammation, lipid metabolism, oxidative stress, insulin resistance and type 2 diabetes, etc. In this review, we focus on the role of miR-27 in the development of vulnerable atherosclerotic plaques, potential as a disease biomarker and novel therapeutic target in atherosclerosis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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.
作者机构:
Institute of Cardiovascular Research,Key Laboratory for Atherosclerology of Hunan Province,Life Science Research Center,University of South China
期刊:
International Journal of Molecular Medicine,2012年29(5):946-956 ISSN:1107-3756
通讯作者:
Tang, Chao-Ke
作者机构:
[Zhao, Guo-Jun; Lv, Yun-Cheng; Jiang, Zhi-Sheng; Tang, Chao-Ke; Yin, Kai; Ouyang, Xin-Ping; Jiang, Jin; Mo, Zhong-Cheng] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.;[Fu, Yuchang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
通讯机构:
[Tang, Chao-Ke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.
关键词:
atherosclerosis;epigallocatechi n-3-gallate;ATP-binding membrane cassette transporter A1;Nrf2/Keap1 pathway;nuclear factor-kappa B
摘要:
The ATP-binding membrane cassette transporter A1 (ABCA1) plays a protective role in the development of atherosclerosis for the reverse cholesterol transport process. Epigallocatechin-3-gallate (EGCG), which exists abundantly in green tea, exerts an anti-atherosclerotic effect via anti-inflammatory and metabolic regulation activities. Many genes and proteins related to lipid metabolism are involved in the lowering cholesterol effects of EGCG. However, effects of EGCG on ABCA1 have rarely been described. In the study presented here, we found that exposure of macrophage foam cells to TNF-α results in a downregulation of ABCA1 and a decrease in cholesterol efflux to apoA1, which is attenuated by pretreatment with EGCG. Moreover, rather than activating the Liver X receptor (LXR) pathway, inhibition of the TNF-α-induced nuclear factor-κB (NF-κB) activity is detected with EGCG treatment in cells. In order to inhibit the NF-κB activity, EGCG can promote the dissociation of the nuclear factor E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) complex; when the released Nrf2 translocates to the nucleus and activates the transcription of genes containing an ARE element inhibition of NF-κB occurs and Keap1 is separated from the complex to directly interact with IKKβ and thus represses NF-κB function. These results provide novel insight into the anti-inflammatory effects of EGCG, as well as the identification of a novel potential therapeutic role for the prevention of atherosclerosis.
作者:
Kai Yin;Zhi-Sheng Jiang;Chao-Ke Tang;Guang-hui Tu;Jing-Feng Li;...
作者机构:
[Kai Yin; Guang-hui Tu; Jing-Feng Li; Wu-Jun Chen; Guo-Jun Zhao; Xin-Ping YangOu; Yun-Cheng LV; Qian Lu; Yuchang Fu; Zhi-Sheng Jiang; Chao-Ke Tang] From Institute of Cardiovascular Research,Key Laboratory for Atherosclerology of Hunan Province,Life Science Research Center,University of South China;[Kai Yin; Guang-hui Tu; Jing-Feng Li; Wu-Jun Chen; Guo-Jun Zhao; Xin-Ping YangOu; Yun-Cheng LV; Qian Lu; Yuchang Fu; Zhi-Sheng Jiang; Chao-Ke Tang] Department of Diagnostics,The Medical College,University of South China;[Kai Yin; Guang-hui Tu; Jing-Feng Li; Wu-Jun Chen; Guo-Jun Zhao; Xin-Ping YangOu; Yun-Cheng LV; Qian Lu; Yuchang Fu; Zhi-Sheng Jiang; Chao-Ke Tang] Department of pathology,Nan Xian Peoples Hospital;[Kai Yin; Guang-hui Tu; Jing-Feng Li; Wu-Jun Chen; Guo-Jun Zhao; Xin-Ping YangOu; Yun-Cheng LV; Qian Lu; Yuchang Fu; Zhi-Sheng Jiang; Chao-Ke Tang] Department of Nutrition Sciences,University of Alabama at Birmingham,Birmingham,AL 35294-0012,USA
会议名称:
第11届全国脂质与脂蛋白学术会议
会议时间:
2012-09-21
会议地点:
太原
会议论文集名称:
第11届全国脂质与脂蛋白学术会议论文集
摘要:
<正>Aims:Apolipoprotein A-I(apoA-I),the major component of high-density lipoprotein(HDL),can suppress the lipopolysaccharide(LPS)-induced inflammatory response in macrophages.The role of apoA-1 in LPS-
作者机构:
[Shi-Lin Tang; Wu-Jun Chen; Kai Yin; Guo-Jun Zhao; Zhong-Cheng Mo; Yun-Cheng Lv; Xin-Ping Ouyang; Chao-Ke Tang] Institute of Cardiovascular Research,Key Laboratory for Atherosclerology of Hunan Province,Life Science Research Center,University of South China
会议名称:
第11届全国脂质与脂蛋白学术会议
会议时间:
2012-09-21
会议地点:
中国山西太原
会议论文集名称:
第11届全国脂质与脂蛋白学术会议论文汇编
摘要:
<正>Pregnancy-associated plasma protein-A(PAPP-A) has been involved in the atherosclerotic process through regulation of local expression of IGF-1 that mediates the activation of the phosphatidylinositol-3(PI3-K ) and Akt kinase(Akt ) signaling cascades which lead to constitutive nitric oxide formation,with its attending vasodilator,antiplatelet and insulin-sensitizing actions.In addition,IGF-1 may decreased cholesterol efflux through reductions of expression in ABCA1 and SR-B1 by the PI3-K/Akt signaling pathway.In the current study,we examined whether
摘要:
Pregnancy-associated plasma protein-A (PAPP-A) has been involved in the atherosclerotic process through regulation of local expression of IGF-1 that mediates the activation of the phosphatidylinositol-3 (PI3-K) and Akt kinase (Akt) signaling cascades which lead to constitutive nitric oxide formation, with its attending vasodilator, antiplatelet and insulin-sensitizing actions. In addition, IGF-1 may decreased cholesterol efflux through reductions of expression in ABCA1 and SR-B1 by the PI3-K/Akt signaling pathway. In the current study, we examined whether PAPP-A was involved in LXRα regulation and in expression of ABCA1, ABCG1 or SR-B1 through the IGF-I-mediated signaling pathway (IGF/PI3-K/Akt). Results showed that PAPP-A significantly decreased expression of ABCA1, ABCG1 and SR-BI at both transcriptional and translational levels in a dose-dependent and time-dependent manner. Cellular cholesterol content was increased while cholesterol efflux was decreased by PAPP-A treatment. Moreover, LXRα which can regulate the expression of ABCA1, ABCG1 and SR-B1, was also down-regulated by PAPP-A treatment. LXRα-specific activation by LXRα agonist almost rescued the down-regulation of ABCA1, ABCG1 and SR-B1 expression by PAPP-A. In addition, PAPP-A can induce the IGF-1/PI3-K/Akt pathway in macrophages. Furthermore, our results indicate that the decreased levels observed in LXRα, ABCA1, ABCG1 and SR-B1 mRNA and protein levels upon treating cells with PAPP-A were strongly impaired with the PI3-K inhibitors or IGF-1R siRNA while the MAPK cascade inhibitor did not execute this effect, indicating that the process of ABCA1, ABCG1 and SR-BI degradation by PAPP-A involves the IGF-1/PI3-K/Akt pathway. In conclusion, PAPP-A may first down-regulate expression of LXRα through the IGF-1/PI3-K/Akt signaling pathway and then decrease expression of ABCA1, ABCG1, SR-B1 and cholesterol efflux in THP-1 macrophage-derived foam cells. Therefore, our study provided one of the mechanisms for understanding the critical effect of PAPP-A in pathogenesis of atherosclerosis.
作者机构:
[Kai; ChaoKe] Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, China
通讯机构:
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, China
关键词:
动脉粥样硬化;心血管疾病;高血压;功能障碍;脂质代谢;中国;炎症;分子机制
摘要:
Atherosclerosis-related cardiovascular disease is one of the leading causes of death in China [1]. With advances in our understanding of the molecular mechanisms of atherosclerosis vascular inflammation, lipid metabolism dysfunction, and hypertension are regarded as the main pathogenetic pathways of both early atherogenesis and advanced plaque rupture [2,3]. Currently, much attention is being paid to the control of these pathways, which offers the potential for development of novel therapeutic approaches in the treatment of cardiovascular disease in China.
期刊:
Journal of Applied Analysis,2011年17(2):155-163 ISSN:1425-6908
通讯作者:
Zhong, J.
作者机构:
Center of Nuclear Energy Economy and Management, University of South China, Hengyang 421001, China;School of Mathematics and Physics, University of South China, Hengyang 421001, China
通讯机构:
Center of Nuclear Energy Economy and Management, University of South China, China
关键词:
Eventually positive solution;Neutral differential equation;Nonlinear;Oscillation;Third-order
期刊:
Journal of Atherosclerosis and Thrombosis,2011年18(9):796-807 ISSN:1340-3478
通讯作者:
Tang, Chao-Ke
作者机构:
[Tang, Chao-Ke; Li, Xiao-Xu; Hu, Yan-Wei; Liu, Xie-Hong; Tang, Ya-Ling; Mo, Zhong-Cheng; Yi, Guang-Hui; Wang, Zuo; Xiao, Ji] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha, Hunan, Peoples R China.
通讯机构:
[Tang, Chao-Ke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词:
Advanced oxidation protein products;ATP-binding cassette transporter A1;JAK/STAT;Cholesterol efflux
摘要:
AIMS: Advanced oxidation protein products (AOPPs) are new independent risk factor for coronary artery disease. This study was to determine the effects and potential mechanisms of AOPPs on cholesterol efflux from human macrophage foam cells. METHODS: Human THP-1 monocytes were preincubated with Phorbol-12-myristate- 13-acetate (PMA) and oxidized low density lipoprotein (ox-LDL) to form foam cells. The protein and mRNA expression were examined by western immunoblotting assays and real-time quantitative PCR, respectively. Cellular cholesterol content was measured by HPLC. The cholesterol efflux was assessed by liquid scintillation counting. RESULTS: AOPPs significantly decreased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1) and liver X receptor alpha (LXRalpha) and reduced cholesterol efflux from THP-1 macrophage- derived foam cells. AOPPs substantially activated NADPH oxidase and activated Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal pathway in THP-1-derived foam-like cells. Inhibiting NADPH oxidase by diphenyliodonium (DPI) effectively abolished the AOPPs-induced decrease in cholesterol efflux and the expression of ABCA1. Inhibiting JAK/STAT activation by its specific inhibitor AG-490 or by siRNA could also block AOPPs action on THP-1 cells. CONCLUSIONS: AOPPs may first down-regulate the expression of LXRalpha and ABCA1 through JAK/STAT signal pathway activation and then inhibit cholesterol efflux in THP-1-derived foam-like cells; therefore, our study may be useful for understanding the critical effects of AOPPs on the pathogenesis of atherosclerosis.
作者机构:
[Zhou, Shouhong; Tian, Shaowen; Ouyang, Xinping; Qiao, Ge; Wang, Ling] Univ S China, Coll Med, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.;[Li, Peng] Univ S China, Coll Life Sci & Technol, Dept Biol, Hengyang 421001, Hunan, Peoples R China.;[Tang, Chaoke; Ouyang, Xinping] Univ S China, Life Sci Res Ctr, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Tian, Shaowen] U;Univ S China, Coll Med, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.
关键词:
Behavioral sensitization;Memory;Morphine;Rapid eye movement sleep deprivation;Sleep
摘要:
Previous studies have shown that behavioral sensitization is modulated by drug-associated context, in which memory processes may be critically involved. Sleep has been suggested to play an important role in memory processes. However, the relationship between sleep and context-modulated effects on behavioral sensitization remains to be elucidated. In the present study, we designed three experiments to explore the effects of rapid eye movement sleep deprivation (RSD) on context-modulated effects on morphine locomotor sensitization in mice. Mice were subjected to 6 h RSD starting either immediately after morphine pairing training or 6 h later. The control mice were returned to their home cages immediately after pairing training and left undisturbed. In experiment 1, RSD from 0 to 6h but not from 7 to 12 h disrupted paired context-modulated enhancement of locomotor activity. In experiment 2, RSD from 0 to 6 h but not from 7 to 12 h disrupted unpaired context-modulated suppression of locomotor activity. In experiment 3, RSD from either 0 to 6h or 7 to 12 h had no effect on conditioned locomotor activity. Our findings suggest that sleep plays a critical role in memory processes underlying context-modulated effects on morphine locomotor sensitization. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
摘要:
The aryl hydrocarbon receptor (AhR) is a period-aryl hydrocarbon receptor nuclear transporter-simple minded domain transcription factor that shares structural similarity with circadian clock genes and readily interacts with components of the molecular clock. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters behavioral circadian rhythms and represses the Period1 (Per1) gene in murine hematopoietic stem and progenitor cells. Per1 expression is driven by circadian locomotor activity cycles kaput-brain muscle ARNT-like (CLOCK-BMAL1)–dependent activation of Eboxes in the Per1 promoter. We hypothesized that the effects of AhR activation on the circadian clock are mediated by disruption of CLOCK-BMAL1 function and subsequent Per1 gene suppression. Effects of AhR activation on rhythmic Per1 transcripts were examined in livers of mice after treatment with the AhR agonist, TCDD; the molecular mechanisms of Per1 repression by AhR were determined in hepatoma cells using TCDD and β-napthoflavone as AhR activators. This study reports, for the first time, that AhR activation by TCDD alters the Per1 rhythm in the mouse liver and that Per1 gene suppression depends upon the presence of AhR. Furthermore, AhR interaction with BMAL1 attenuates CLOCK-BMAL1 activity and decreases CLOCK binding at Ebox1 and Ebox3 in the Per1 promoter. Taken together, these data suggest that AhR activation represses Per1 through disrupting CLOCK-BMAL1 activity, producing dysregulation of rhythmic Per1 gene expression. These data define alteration of the Per1 rhythm as novel signaling events downstream of AhR activation. Downregulation of Per1 could contribute to metabolic disease, cancer, and other detrimental effects resulting from exposure to certain environmental pollutants.