期刊文献+

前蛋白转化酶枯草溶菌素9小分子干扰RNA对血管平滑肌细胞增殖的影响 被引量:4

Effect of PCSK9 siRNA on proliferation of vascular smooth muscle cells
下载PDF
导出
摘要 目的研究前蛋白转化酶枯草溶菌素9(PCSK9)基因沉默后对血管平滑肌细胞(VSMC)增殖的影响,初步探讨低密度脂蛋白受体相关蛋白1(LRP-1)蛋白表达在其中的作用。方法建立PCSK9小分子干扰RNA(siRNA)模型,培养VSMC,分为空白对照组、阴性转染组和阳性转染组,选取转染效率最高的PCSK9siRNA对VSMC进行干预,分别于12、24、36、48、60h用MTT法测定吸光度(A)值,绘制增殖曲线,观察其对VSMC增殖的影响,转染48h后用Western blot印迹法检测细胞内LRP-1蛋白表达情况。结果与阴性转染组比较,阳性转染组24、36、48和60h的A值明显下降(P<0.05),PCSK9siRNA抑制VSMC的增殖(P<0.05)。与空白对照组和阴性转染组比较,阳性转染组LRP-1蛋白表达明显上调(P<0.05)。结论 PCSK9siRNA能有效抑制VSMC的增殖作用,且这种作用可能与LRP-1蛋白表达上调有一定的关系。 Objective To study the effect of PCSK9 siRNA on proliferation of vascular smooth muscle cells(VSMC)and the role of LRP-1expression in proliferation of VSMC.Methods After a PCSK9 siRNA model was established,the cultured VSMC were divided into blank control group,negative transfection group and positive transfection group.The absorbance value(A)of VSMC was detected by MTT assay.Curves of proliferative VSMC were plotted.Effect of PCSK9 siRNA on proliferation of VSMC was detected at hours 12,24,36,48,60 respectively.LRP-1expression in VSMC was detected by Western blot at 48 hafter transfection.Results The Avalue was significantly lower in positive transfection group than in negative transfection group at hours24,36,48 and 60(P〈0.05).The LRP-1expression level was significantly higher in positive transfection group than in blank control group and negative transfection group(P〈0.05).Conclusion PCSK9 siRNA can effectively inhibit the proliferation of VSMC by up-regulating the LRP-1 expression.
出处 《中华老年心脑血管病杂志》 CAS 2016年第7期734-738,共5页 Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金 湖南省2014年科技创新项目(2014658) 2012年仁术科研发展基金(201219)
关键词 前蛋白转化酶类 RNA 小分子干扰 基因沉默 肌细胞 平滑肌 平滑 血管 LDL受体相关蛋白质1 proprotein convertases RNA small interfering gene silencing myocytes smooth muscle muscle smooth vascular LDL-receptor related protein 1
  • 相关文献

参考文献20

  • 1Duff CJ,Hooper NM.PCSK9:an emerging target for treatment of hypercholesterolemia[J].Expert Opin Ther Targets,2011,15:157-168.
  • 2Mousavi SA,Berge KE,Leren TP.The unique role of proprotein convertase subtilisin/kexin 9in cholesterol homeostasis.J Intern Med,2009,266:507-519.
  • 3Brown MS,Goldstein JL.Biomedicine.Lowering LDL--not only how low,but how long?Science,2006,311:1721-1723.
  • 4张浩,王志维,吴红兵,胡小平,任宗力,李罗成,周桢,胡志鹏,李柏军.大鼠血管平滑肌细胞的培养和鉴定[J].武汉大学学报(医学版),2014,35(3):378-380. 被引量:6
  • 5Hu X,Wang Z,Wu H,et al.Ras ssDNA aptamer inhibits vascular smooth muscle cell proliferation and migration through MAPK and PI3K pathways.Int J Mol Med,2015,35:1355-1361.
  • 6Katz G,Harchandani B,Shah B.Drug-eluting stents:the past,present,and future.Curr Atheroscler Rep,2015,17:485.
  • 7Abifadel M,Varret M,Rabès JP,et al.Mutations in PCSK9cause autosomal dominant hypercholesterolemia.Nat Genet,2003,34:154-156.
  • 8Denis M,Marcinkiewica J,Zaid A,et al.Gene inactivation of proprotein convertase subtilisin/kexin type 9reduces atherosclerosis in mice.Circulation,2012,125:894-901.
  • 9Cannon CP,Cariou B,Blom D,et al.Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins:the ODYSSEY COMBOⅡrandomized controlled trial.Eur Heart J,2015,36:1186-1194.
  • 10Raal FJ,Stein EA,Dufour R,et al.PCSK9inhibition with evolocumab(AMG 145)in heterozygous familial hypercholesterolaemia(RUTHERFORD-2):a randomised,double-blind,placebo-controlled trial.Lancet,2015,385:331-340.

二级参考文献66

  • 1王云雅,汪静,邓敬兰,李国权,林国成,顾春虎.放射性PDGFR-β反义寡核苷酸对血管平滑肌细胞增殖和凋亡的影响[J].心脏杂志,2006,18(4):388-391. 被引量:4
  • 2程艳丽,谢闵,刘录山,王贵学.pcsk9基因突变与胆固醇血症[J].中国生物化学与分子生物学报,2007,23(3):172-176. 被引量:6
  • 3李英,段惠军.Raf/MEK/ERK信号转导通路在糖尿病肾病发生发展中的作用[J].国际内分泌代谢杂志,2007,27(4):269-272. 被引量:7
  • 4Elagoz A, Benjannel S, Mammarbassi A, et al. Biosynthesis and cellular trafficking of the convertase SKI-1/SIP: eetodomain shedding requires SKI-1activity. J Biol Chem, 2002, 277 (13): 11265- 11275
  • 5Seidah N G, Benjannet S, Wickham L, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation.Proc Natl Acad Sci USA, 2003, 100(3): 928-933
  • 6Maxwell K N, Fisher E A, Breslow J L, et al. Over expression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc Natl Acad Sci USA, 2005, 102(6): 2069-2074
  • 7Poirier S, Prat A, Marcinkiewicz E, et al. Implication of the proprotein convertase PCSK9/NARC-1 in the development of the nervous system. J Neurochem, 2006, 98(3): 838-850
  • 8Peterson A S, Fong L G, Young S G. PCSK9 function and physiology. J Lipid Res, 2008, 49(6): 1152- 1156
  • 9Bingham B, Shen R, Kotnis S, et al. Proapoptotic effects ofNARC 1 (= PCSKg), the gene encoding a novel serine proteinase. Cytometry A, 2006, 69(11): 1123-1131
  • 10Brown M S, Goldstein J L. Lowing LDL-not only how low, but how long?. Science, 2006, 311(5768): 1721 - 1723

共引文献30

同被引文献31

引证文献4

二级引证文献12

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部