Activation of peroxisome proliferator-activated receptor α in human endothelial cells increases plasminogen activator inhibitor type-1 expression

Objective To investigate the effect of peroxisome proliferator-activated receptors(PPARs) activators on plasminogen activator inhibitor 1(PAI-1) expression in human umbilical vein endothelial cells and elucidate a possible mechanism.Methods Human umbilical vein endothelial cells(HUVECs) were obtained from normal fetus,and cultured conventionally.Then the HUVEC were exposed to fatty acids and prostaglandin J2 in varying concentrations with fresh media.RT-PCR and ELISA were used to determine the expression of PPAR and PAI-1 in HUVECs.Transient co-transfection of PAI-1 promoter and PPARα gene or PPARγ gene to ECV304 was performed.Results PPARα,PPARγ and PPARγ mNRA in HUVECs were detected by RT-PCR.Treatment of HUVECs with PPARα and PPARγ activators-linolenic acid,linoleic acid,oleic acid and prostaglandin J2,but not with stearic acid could augment PAI-1 mRNA expression and protein secretion in a concentrationdependent manner.Proportional induction of PAI-1 promoter activity was observed through increasing amounts of PPARαDNA in HUVECs throgh a transient gene transfection assay,although the mRNA expression of the 3 subtypes of PPAR with their activators were not changes compared with controls.Conclusions HUVECs express PPARs,PPARs activators may increase PAI-1 expression in endothelial cells(EC).Although PPARs expresslon was not enhanced after being stimulated by their activators in EC,the functionally active PPARαis probably involved in regulating PAI-1 expression in EC.     

PPARγ与肿瘤血管生成

过氧化物酶体增殖物活化受体 (peroxisomeproliferators ac tivatedreceptors ,PPARs)是属于核激素受体 (nuclearhormonere ceptor)超家族的成员。在 1990年由英国科学家Issemann和Green首先发现[1] 。目前已知两栖类、啮齿类动物及人类PPAR均存在三种亚型 ,即PPARα、PPARγ及PPARδ(亦称PPARβ) ,其中PPARγ是人们研究最广泛的一种 ,特别是近年来 ,通过使用PPARγ激动剂来抑制新生血管的生成显示了良好的应用前景。本文拟对此综述如下。1　PPARγ的概述1.1　PPARγ结构及组织分布　PPARγ在PPARs中是最具脂肪组织特异…     

PPARγ与肺纤维化

过氧化物酶体增殖物激活受体(peroxisome proliferators-activated receptor,PPAR)是一类由配体激活的核转录因子超家族成员,属Ⅱ型核受体超家族成员.PPARs有3种表型,即PPARα、VPARβ(亦称PPARδ)和PPARγ.     

Blockage of PPARδ increases the expression of inflammatory factors in 3T3-L1 cells stimulated with TNFα

Objective: To investigate the role of peroxisome proliferator-activated receptors δ (PPARδ) in inflammatory reaction and its possible mechanism in adipocyte. Methods :Lentivirus-mediated RNA interference (RNAi) was used to block the expression of PPARS in 3T3-L1 cells. In order to induce inflammation in 3T3-L1, cells were stimulated with tumor necrosis factor-α(TNFα, 20 ng/ml) for 4 h. The expression of PPAR8, nuclear factor κB (NFκB) and C reactive protein (CRP) were determined by Western blot analysis. Results:The expression of PPARδ was reduced by 80% after RNAi. Blockage of PPARδ promoted the expression of CRP and NFκB in cells stimulated with TNFα, but had no effect on normal cells. Conclusion: PPARδ is involved in inflammatory reaction in adipocyte. Blockage of PPARδ can promote the inflammation mediated by inflammatory factors and increase the expression of NFκB and CRP in 3T3-L1 cells stimulated with TNFα.     

Blockage of PPAR8 increases the expression of-inflammatory factors in 3T3-L1 cells stimulated with TNFα

Objective： To investigate the role of peroxisome proliferator-activated receptors δ （PPARδ） in inflammatory reaction and its possible mechanism in adipocyte. Methods：Lentivirus-mediated RNA interference （RNAi） was used to block the expression of PPARδ in 3T3-L1 cells. In order to induce inflammation in 3T3-L1, cells were stimulated with tumor necrosis factor-α（TNFα, 20 ng/ml） for 4 h. The expression of PPARδ, nuclear factor κB （NFκB） and C reactive protein （CRP） were determined by Western blot analysis. Results：The expression of PPARδ was reduced by 80% after RNAi. Blockage of PPARδ promoted the expression of CRP and NFκB in cells stimulated with TNFα but had no effect on normal cells. Conclusion： PPARδ is involved in inflammatory reaction in adipocyte. Blockage of PPARδ can promote the inflammation mediated by inflammatory factors and increase the expression of NFκB and CRP in 3T3-L1 cells stimulated with TNFα.     

糖尿病心肌病患者过氧化物酶增殖物激活受体水平变化的研究

目的 观察糖尿病心肌病（DCM）患者过氧化物酶增殖物激活受体（PPARs）水平变化,并探讨其影响DCM的可能机制。方法 选取2016年10月—2017年10月郑州大学附属南阳市中心医院住院治疗的DCM患者（DCM组）74例、单纯糖尿病患者（T2DM组）71例和同期健康体检者（NC组）70例,收集各组一般资料,采用ELISA检测PPARs水平并比较。结果 DCM组空腹血糖（FPG）、糖化血红蛋白（HbA1c）、甘油三酯（TG）及高敏感C反应蛋白（hs-CRP）高于T2DM组和NC组（P?<0.05）,T2DM组FPG、HbA1c及TG高于NC组（P?<0.05）;DCM组PPARα和PPARγ高于T2DM组和NC组（P?<0.05）,PPARβ/δ低于T2DM组和NC组,且T2DM组PPARα和PPARγ高于NC组,PPARβ/δ低于NC组（P?<0.05）。结论 DCM患者PPARα和PPARγ水平升高,PPARβ/δ水平降低,PPARs可能在DCM的发生、发展中起到重要作用。     

Inflammatory reaction versus endogenous peroxisome proliferator- activated receptors expression, re-exploring secondary organ complications of spontaneously hypertensive rats

Background The chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors （PPARs） have been identified： PPARa, PPARβ/δ, and PPARγ, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats （SHR） and to understand the modulation of endogenous PPAR isoforms under inflammatory condition. Methods l]ssues （kidney, liver, heart, and brain） were dissected from SHR and age-matched control Wistar-Kyoto rats （WKY） to investigate the abundance of PPAR isoforms and PPAR-responsive genes （acyI-CoA oxidase and CD36）. The expression of CCAAT/enhancer-binding protein 6 （C/EBP6）, which can trans-activate PPARγ expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase （iNOS）, intercellular adhesion molecule-1 （ICAM-1）, vascular cell adhesion molecule-1 （VCAM-1）, E-selectin, interleukin-1 beta （IL-1β）, and tumor necrosis factor alpha （TNFα）, and formation of carbonyl and nitrated proteins. Results The expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARa protein in the kidney, liver, heart and brain increased by 130.76 %, 91.48%, 306.24%, and 90.70%; PPARβ/δ upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARγ increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARy, the expression of C/EBPδ was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of     

PPARs和NFкB在高脂血症大鼠内皮细胞中表达的研究

目的:探讨核转录因子PPARα、PPARγ和NFκB在正常及高脂血症大鼠主动脉内皮细胞中表达的变化以及fibrate干预后炎性因子IL-6的变化.方法:取正常及高脂血症大鼠模型主动脉冰冻切片行免疫组化分析PPARα、PPARγ、NFκB和IL-6的表达,PPARs的人工合成配体Gemfibrate和Bzafibrate干预后的变化及其关系.结果:正常大鼠主动脉上有PPARα、PPARγ、NFκB和IL-6的弱表达.高脂血症时,主动脉内皮细胞层PPARα、PPARγ、NFκB、IL-6的表达增强,其OD值较正常大鼠显著增加(P＜0.05),NFκB的活化明显.Fibrates药物干预后,血脂下降(除HDL),PPARα、PPARγ进一步活化,IL-6的表达减弱,对NFκB的表达无明显影响.结论:核转录因子PPARs和NFκB在高脂血症人鼠内皮细胞中均显著增加.Fi-brates类药物可通过活化相应受体PPARs部分抑制炎性因子的分泌.     

过氧化物酶体增殖物激活受体与糖脂代谢

1　分类、结构、基因和基因表达1.1　分类　过氧化物酶体增殖物激活受体 (PPARs)是一组由四种异构体组成的配体激活的核受体 ,即α、β(δ或hNUC1)、γ1、γ2 ,属于Ⅱ型核受体超家族成员 ,由各自不同的基因编码[1 ] 。1.2　结构　PPARs在结构上由 3个结构域组成 ,即DNA结合区域、基因活化区域和配体结合区域。PPAR为 4 4 1个氨基酸的蛋白质 ,与过氧化物酶体增殖物反应元件 (PPRE)结合区含有 2个锌指结构 ,故属于核受体家族的转录因子[2 ] 。1.3　基因　编码PPARα的基因定位于染色体 2 2q ,编码鼠PPARβ的基因由含有 30kb以上的…     

EFFECT OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ACTIVATORS ON TUMOR NECROSIS FACTOR-α EXPRESSION IN NEONATAL RAT CARDIAC MYOCYTES

Objective To investigate the effect ofperoxisome proliferator-activated receptor-α (PPARα) and PPARγ activators on tumor necrosis factor-α (TNFα) expression in neonatal rat cardiac myocytes.Methods Primary cultures of cardiac myocytes from 1- to 3-day-old Wistar rats were prepared, and myocytes were exposed to lipopolysaccharide (LPS) and varying concentrations of PPARα or PPARγ activator (fenofibrate or pioglitazone).RT-PCR and ELISA were used to measure TNFα, PPARα, and PPARγexpression in cultured cardiac myocytes. Transient transfection of TNFα promoter with or without nuclear factor-kappaB (NF-κB) binding site to cardiac myocytes was performed.Results Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNFα mRNA and protein expression in a dose-dependent manner. However, no significant changes were observed on PPARα or PPARγ mRNA expression when cardiac myocytes were pretreated with fenofibrate or pioglitazone. Proportional suppression of TNFαpromoter activity was observed when myocytes was transiently transfected with whole length of TNFα promoter (-721/ 17) after being stimulated with LPS and fenofibrate or pioglitazone, whereas no change of promoter activity was observed with transfection of TNFα reporter construct in deletion of NF-κB binding site (-182/ 17).Conclusions PPARα and PPARγ activators may inhibit cardiac TNFα expression but not accompanied by change of PPARα or PPARγmRNA expression. Therefore PPARα and PPARγ activators appear to play a role in anti-inflammation.The mechanism may partly be involved in suppression of the NF-κB pathway.     

新型过氧化物酶体增殖物激活受体激动剂阿格列扎

本文阐述了过氧化物酶体增殖物激活受体(Peroxisome proliferator activated receptors,PPARs)概念、PPARs激动剂种类及新型PPARα/γ双激动剂阿格列扎的最新研究进展.     

PPARs和NFκB在高脂血症大鼠内皮细胞中表达的研究

目的 :探讨核转录因子PPARα、PPARγ和NFκB在正常及高脂血症大鼠主动脉内皮细胞中表达的变化以及fibrate干预后炎性因子IL - 6的变化。方法 :取正常及高脂血症大鼠模型主动脉冰冻切片行免疫组化分析PPARα、PPARγ、NFκB和IL - 6的表达 ,PPARs的人工合成配体Gemfibrate和Bezafibrate干预后的变化及其关系。结果 :正常大鼠主动脉上有PPARα、PPARγ、NFκB和IL - 6的弱表达。高脂血症时 ,主动脉内皮细胞层PPARα、PPARγ、NFκB、IL - 6的表达增强 ,其OD值较正常大鼠显著增加 (P <0 .0 5 ) ,NFκB的活化明显。Fibrates药物干预后 ,血脂下降 (除HDL) ,PPARα、PPARγ进一步活化 ,IL - 6的表达减弱 ,对NFκB的表达无明显影响。结论 :核转录因子PPARs和NFκB在高脂血症人鼠内皮细胞中均显著增加。Fi brates类药物可通过活化相应受体PPARs部分抑制炎性因子的分泌。     

过氧化物酶体增殖物激活受体β在中枢神经系统疾病中的作用

过氧化物酶体增殖物激活受体（peroxisome proliferator activated receptors,PPARs）是一类核受体超家族,其成员有PPARα、PPARβ（也称为PPARδ）和PPARγ 3种亚型。PPARs自被发现以来受到广泛关注并在各个领域展开研究,其中主要集中在PPARα和PPARγ的研究上,对其在体内的病理生理作用都有了比较深刻的了解,其部分配体也已广泛用于临床治疗,而对PPARβ的研究相对较少。近来有学者认为PPARβ是PPARα和PPARγ激活的连接枢纽,使得其地位更加重要,PPARβ在中枢神经系统疾病中的作用及其调控机制越来越引起人们的关注。但关于PPARβ在中枢神经系统疾病中的作用及机制的研究却远落后于其他2种亚型。本文就PPARβ在中枢神经系统疾病中的作用进行综述。     

过氧化物酶体增殖物激活受体与动脉粥样硬化的相关研究进展

过氧化物酶体增殖物激活受体(Peroxisome proliferator activated receptors,PPARs)是一类由配体激活的核转录因子超家族成员.PPARs有三种亚型:PPARα、PPARβ、PPARγ.PPARs主要参与代谢的调节,如调节脂质代谢、平滑肌的迁移与增殖、血管内皮功能、炎症反应、高血压等,在血管、心脏、肌肉、肾脏等的组织均有表达.下面就PPARs与动脉粥样硬化(Atherosclerosis,AS)的相关性研究进展作一综述.     

PPARγ及其激动剂与消化系统肿瘤

过氧化物酶体增殖物激活受体（peroxisome proliferator actived receptors，PPARs），是由英国科学家Issemann和Green于1990年首先发现的。该受体是由配体激动，有3种亚型：PPARα、PPARγ和PPARβ/δ。PPARγ生物学功能复杂，最具有脂肪组织特异性，参与脂肪和糖的代谢、抑制炎症反应、抗肝纤维化作用、抗动脉粥样硬化等。近来研究发现PPARγ在多种肿瘤组织中表达，其与配体结合活化后，可抑制多种恶性肿瘤细胞的生长。     

过氧化物酶体增殖物激活受体γ激动剂与终末期肾脏病

过氧化物酶体增殖物激活受体（Peroxisome Proliferator—Activated Receptors，PPARs）是一种细胞核受体，已知其包括PPARα、PPARδ、PPARγ三种类型，其中PPAR-γ除了主要在脂肪组织表达外，在肝脏、肾脏、血管内皮细胞及巨噬细胞中也有表达。PPAR-γ激动剂主要通过增加胰岛素敏感性而调节机体血糖代谢，同时在抗炎、抗纤维化、降低蛋白尿、抗动脉粥样硬化等方面也发挥着重要作用。