我们的网站为什么显示成这样?

可能因为您的浏览器不支持样式,您可以更新您的浏览器到最新版本,以获取对此功能的支持,访问下面的网站,获取关于浏览器的信息:

|本期目录/Table of Contents|

GDF11逆转巨噬细胞胆固醇堆积的分子机制研究

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2016年第5期
页码:
503-507
栏目:
基础研究
出版日期:
2016-04-25

文章信息/Info

Title:
Effect of GDF11 on cholesterol accumulation in macrophages
作者:
王贺林12张 玲1张富洋1汪 雄1刘朝中3陶 凌1
(1.第四军医大学西京医院心血管内科,陕西 西安 710032;
2.解放军95806部队门诊部,北京 100076;
3.空军总医院介入诊疗中心,北京 100142)
Author(s):
WANG He-lin12 ZHANG Ling1 ZHANG Fu-yang1 WANG Xiong1 LIU Chao-zhong3 TAO Ling1
(1.Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China;
2.Outpatient Department of Unit 95806, Beijing 100076, China;
3.Interventional Center, General Hospital, Air Force, Beijing 100142, China)
关键词:
GDF11动脉粥样硬化心血管疾病
Keywords:
GDF11 atherosclerosis cardiovascular disease
分类号:
Q51
DOI:
-
文献标识码:
A
摘要:
目的 观察生长转化因子(GDF)11在巨噬细胞泡沫化中的作用并探讨其可能的分子机制。方法 以不同浓度氧化型低密度脂蛋白(oxLDL)处理RAW264.7细胞,将75 μg/ml oxLDL与不同浓度GDF11共处理过夜,采用荧光染色观察巨噬细胞脂质堆积情况。提取总蛋白或是总RNA,采用Western blot方法检测oxLDL对巨噬细胞GDF11表达的作用,采用实时荧光定量PCR检测GDF11、ABCA1、ABCG1、CD36、IL-1、IL-6及MMP9 mRNA的表达。结果 oxLDL可以显著诱导巨噬细胞胆固醇堆积并抑制巨噬细胞GDF11表达(P<0.05),外源给予GDF11可以抑制oxLDL引起的巨噬细胞胆固醇堆积(P<0.05);oxLDL孵育能够有效诱导CD36、IL-1、IL-6和MMP9 mRNA表达并抑制ABCA1、ABCG1 mRNA表达(P<0.05),外源给予GDF11刺激可以有效逆转oxLDL对于CD36、IL-1、IL-6和MMP9 mRNA的诱导和对于ABCA1、ABCG1 mRNA的抑制(P<0.05)。结论 GDF11可以有效抑制巨噬细胞泡沫化进程,与其有效逆转oxLDL对于CD36、IL-1、IL-6和MMP9 mRNA的诱导和对于ABCA1、ABCG1 mRNA的抑制相关。
Abstract:
AIM To investigate the effect of GDF11 on the progression of foam cell formation and to explore the underlying mechanism. METHODSRAW264.7 cells were treated with oxLDL at indicated concentrations or with 75 μg/ml oxLDL and GDF11 at indicated concentrations overnight. Lipid-laden macrophages were detected by immunofluorescent method. Cellular total protein and RNA were extracted. The effect of oxLDL on GDF11 expression was detected by Western blot and the expressions of GDF11, ABCA1, ABCG1, CD36, IL-1, IL-6 and MMP9 mRNA were examined by real-time PCR. RESULTSOxLDL promoted the formation of foam cells and inhibited the expression of GDF11 (P<0.05). However, the exogenous supply of GDF11 inhibited the inducing effect of oxLDL on foam cell formation (P<0.05). oxLDL induced the expression of CD36, IL-1, IL-6 and MMP9 mRNA expressions and inhibited ABCA1 and ABCG1 mRNA expressions (P<0.05). The exogenous supply of GDF11 could reverse the inducing effect of oxLDL on CD36, IL-1, IL-6 and MMP9 mRNA expressions and the inhibitory effect on ABCA1 and ABCG1 mRNA expressions (P<0.05). CONCLUSIONGDF11 can inhibit the progression of foam cell formation induced by oxLDL possibly through its reverse effect on oxLDL-induced CD36, IL-1, IL-6 and MMP9 mRNA expressions and reduction of ABCA1 and ABCG1 mRNA expressions.

参考文献/References

[1]Ilhan F,Kalkanli ST.Atherosclerosis and the role of immune cells[J].World J Clin Cases,2015,3(4):345-352.
[2]McPherron AC,Lawler AM,Lee SJ.Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11[J].Nat Genet,1999,22(3):260-264.
[3]Wu HH,Ivkovic S,Murray RC,et al.Autoregulation of neurogenesis by GDF11[J].Neuron,2003,37(2):197-207.
[4]Weiss MJ,dos Santos CO.Chaperoning erythropoiesis[J].Blood,2009,113(10):2136-2144.
[5]Nakashima M.The induction of reparative dentine in the amputated dental pulp of the dog by bone morphogenetic protein[J].Arch Oral Biol,1990,35(7):493-497.
[6]Loffredo FS,Steinhauser ML,Jay SM,et al.Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy[J].Cell,2013,153(4):828-839.
[7] Rungoe C,Nyboe Andersen N,Jess T.Inflammatory bowel disease and risk of coronary heart disease[J].Trends Cardiovasc Med,2015,25(8):699-704.
[8]Bessueille L,Magne D.Inflammation:a culprit for vascular calcification in atherosclerosis and diabetes[J].Cell Mol Life Sci,2015,72(13):2475-2489.
[9]B?ck M,Hansson GK.Anti-inflammatory therapies for atherosclerosis[J].Nat Rev Cardiol,2015,12(4):199-211.
[10]Abilleira S,Bevan S,Markus HS.The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis[J].J Med Genet,2006,43(12):897-901.
[11]Park YM. CD36, a scavenger receptor implicated in atherosclerosis [J]. Exp Mol Med, 2014, 46:e99.
[12]Westerterp M,Bochem AE,Yvan-Charvet L,et al.ATP-binding cassette transporters,atherosclerosis, and inflammation[J].Circ Res,2014,114(1):157-170.

备注/Memo

备注/Memo:
收稿日期:2015-10-20.
基金项目:国家杰出青年科学基金项目资助(81225001);国家自然科学基金项目资助(81503064)
通讯作者:陶凌,教授,主要从事糖尿病与心血管保护研究 Email:lingtao@fmmu.edu.cn 共同
通讯作者:刘朝中,教授,主要从事冠心病的介入治疗和病理研究 Email:liu_chaozhong@sohu.com
作者简介:王贺林,硕士生 Email:921441502@qq.com
更新日期/Last Update: 2016-04-13