Advances in the role of miRNAs in myocardial infarction and its mechanisms

doi:10.3877/cma.j.issn.2095-1221.2019.06.008

Abstract

Abstract:

Acute myocardial infarction (AMI) is the most common cardiovascular event with high morbidity and mortality, which is a serious threat to human health. MicroRNAs (miRNAs) act as an important role by regulating cardiomyocyte inflammatory and fibrosis, regulation of autophagy and neovascularization. Here, we review the molecular mechanisms of up-regulation and down-regulation of miRNA after myocardial infarction and the early diagnostic value of miRNA for myocardial infarction

Key words: MicroRNA, Biomarkers for diagnosis, Myocardial infarction, Molecular mechanism, Exosomes

Runfeng Cao, Li Shen. Advances in the role of miRNAs in myocardial infarction and its mechanisms[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2019, 09(06): 363-368.

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URL: https://zhxbygxbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-1221.2019.06.008

https://zhxbygxbzz.cma-cmc.com.cn/EN/Y2019/V09/I06/363

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References 81

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miRNA	临床研究样本分析		引文
miRNA	AMI样本数	对照组样本数	引文
miR-22-5p，miR-132-5p，miR-150-3p	35	55	[9]
miR-26a-1，miR-146a和miR-199a-1	31	27	[10]
miR-17-5p，miR-126-5p，miR-145-3p	29	21	[11]
miR-150	59	59	[12]
miRNA-4478	80	80	[13]
miRNA-302b	76	30	[14]
miRNA-133a	102	110	[15]
miR-208b	100	80	[16]
miR-221-3p	27	16	[17]

miRNA	临床研究样本分析		引文
miRNA	AMI样本数	对照组样本数	引文
miR-22-5p，miR-132-5p，miR-150-3p	35	55	[9]
miR-26a-1，miR-146a和miR-199a-1	31	27	[10]
miR-17-5p，miR-126-5p，miR-145-3p	29	21	[11]
miR-150	59	59	[12]
miRNA-4478	80	80	[13]
miRNA-302b	76	30	[14]
miRNA-133a	102	110	[15]
miR-208b	100	80	[16]
miR-221-3p	27	16	[17]

miRNA	研究对象	信号通路及靶点	作用细胞	效应机制	引文
miR-21	小鼠	TGF-β/ Smad7信号通路	心脏成纤维细胞	抑制心脏纤维化	[20]
miR-23a	小鼠	锰超氧化物歧化酶（MnSOD）	心肌细胞	抑制心肌凋亡	[21]
miR-92a	小鼠	自噬及代谢相关基因	内皮细胞心肌细胞	抑制自噬，调节代谢	[22]
miR-125b miR-125b-5p	小鼠	抑制促凋亡基因p53和BAK1及调节p53-Bnip3信号传导，抑制bak1和klf13基因	心肌细胞	抑制心肌细胞凋亡	[23,24] [25]
miR-132	小鼠	调节Akt / eNOS / Bcl-2信号传导途径，抑制Ras-GTP酶活化蛋白和甲基-CpG结合蛋白2	内皮细胞	促进血管形成	[26]
miR-146b	小鼠	靶向Notch1	心肌细胞	抗凋亡及抑制炎症反应	[27]
miR-199a	小鼠	靶向GSK3β / mTOR信号传导及抑制Atg5	心肌细胞	抑制自噬及心肌肥大	[28]
miR-499	大鼠H9c2细胞	靶向SOX6,上调Bcl-2水平及下调Bax和caspase-3的表达水平	心肌细胞	抑制凋亡	[29]
miR-133a	大鼠	调节TGF-β1，Caspase9和Caspase3	心肌细胞成纤维细胞	抑制凋亡抑制心肌纤维化	[30]
miR-144 miR-451	小鼠	靶向调节CUGBP2-COX-2	心肌细胞	抑制心肌凋亡	[31]
miR-138	先心病心肌样本+ H9C2细胞	靶向MLK3/JNK /c-jun通路	心肌细胞	抑制心肌凋亡	[32]
miR-874	小鼠	靶向STAT3-JAK2 / STAT3信号传导途径	心肌细胞	抑制心肌凋亡	[33]
miR-26a	大鼠	调节Wnt信号通路，抑制GSK3β表达和促进Cx43表达	心肌细胞	降低心肌细胞的损伤	[34]
miR-210	小鼠	增加中性鞘磷脂酶2（nSMase2）的表达	心肌细胞心脏内皮细胞、成纤维细胞	抑制凋亡，增加新生血管密度，抑制心脏纤维化	[35]
miR-19a	大鼠	靶向PTEN的表达，激活Akt / ERK信号传导途径	心肌细胞	减少心肌细胞凋亡和维持线粒体膜电位	[36]
miR-126	缺血性心肌病裸鼠	促进HGF，TIMP-1/TIMP-2的表达	内皮细胞	促进新生血管形成，降低炎症反应	[37]
miR-21	小鼠	靶向抑制PDCD4	心肌细胞	抑制心肌细胞自噬	[38]
miR-126	小鼠	抑制Spred-1的表达来增强VEGF和FGF的促血管生成	内皮细胞	诱导内皮细胞的微血管形成和迁移	[39]
miR-214	心梗患者血清	抑制PUMA，PTEN，Bax和caspase 7基因的表达	心肌细胞	抑制心肌细胞的凋亡	[40]
miR-208b	大鼠	抑制GATA4	心脏成纤维细胞	抑制心肌纤维化	[41]
miR-211	大鼠	STAT3 / miR-211 / STAT5A信号传导	间充质干细胞	降低MI后不良重建	[42]
miR-206	大鼠	靶向Pim-1激酶	间充质干细胞	刺激细胞循环并增强体内心脏再生	[43]
miR-532	小鼠	调节miR-532-prss23轴	内皮-间质转化（EndMT）	减少EndMT，增加内皮细胞增值及新生血管的密度	[44]

miRNA	研究对象	信号通路及靶点	作用细胞	效应机制	引文
miR-21	小鼠	TGF-β/ Smad7信号通路	心脏成纤维细胞	抑制心脏纤维化	[20]
miR-23a	小鼠	锰超氧化物歧化酶（MnSOD）	心肌细胞	抑制心肌凋亡	[21]
miR-92a	小鼠	自噬及代谢相关基因	内皮细胞心肌细胞	抑制自噬，调节代谢	[22]
miR-125b miR-125b-5p	小鼠	抑制促凋亡基因p53和BAK1及调节p53-Bnip3信号传导，抑制bak1和klf13基因	心肌细胞	抑制心肌细胞凋亡	[23,24] [25]
miR-132	小鼠	调节Akt / eNOS / Bcl-2信号传导途径，抑制Ras-GTP酶活化蛋白和甲基-CpG结合蛋白2	内皮细胞	促进血管形成	[26]
miR-146b	小鼠	靶向Notch1	心肌细胞	抗凋亡及抑制炎症反应	[27]
miR-199a	小鼠	靶向GSK3β / mTOR信号传导及抑制Atg5	心肌细胞	抑制自噬及心肌肥大	[28]
miR-499	大鼠H9c2细胞	靶向SOX6,上调Bcl-2水平及下调Bax和caspase-3的表达水平	心肌细胞	抑制凋亡	[29]
miR-133a	大鼠	调节TGF-β1，Caspase9和Caspase3	心肌细胞成纤维细胞	抑制凋亡抑制心肌纤维化	[30]
miR-144 miR-451	小鼠	靶向调节CUGBP2-COX-2	心肌细胞	抑制心肌凋亡	[31]
miR-138	先心病心肌样本+ H9C2细胞	靶向MLK3/JNK /c-jun通路	心肌细胞	抑制心肌凋亡	[32]
miR-874	小鼠	靶向STAT3-JAK2 / STAT3信号传导途径	心肌细胞	抑制心肌凋亡	[33]
miR-26a	大鼠	调节Wnt信号通路，抑制GSK3β表达和促进Cx43表达	心肌细胞	降低心肌细胞的损伤	[34]
miR-210	小鼠	增加中性鞘磷脂酶2（nSMase2）的表达	心肌细胞心脏内皮细胞、成纤维细胞	抑制凋亡，增加新生血管密度，抑制心脏纤维化	[35]
miR-19a	大鼠	靶向PTEN的表达，激活Akt / ERK信号传导途径	心肌细胞	减少心肌细胞凋亡和维持线粒体膜电位	[36]
miR-126	缺血性心肌病裸鼠	促进HGF，TIMP-1/TIMP-2的表达	内皮细胞	促进新生血管形成，降低炎症反应	[37]
miR-21	小鼠	靶向抑制PDCD4	心肌细胞	抑制心肌细胞自噬	[38]
miR-126	小鼠	抑制Spred-1的表达来增强VEGF和FGF的促血管生成	内皮细胞	诱导内皮细胞的微血管形成和迁移	[39]
miR-214	心梗患者血清	抑制PUMA，PTEN，Bax和caspase 7基因的表达	心肌细胞	抑制心肌细胞的凋亡	[40]
miR-208b	大鼠	抑制GATA4	心脏成纤维细胞	抑制心肌纤维化	[41]
miR-211	大鼠	STAT3 / miR-211 / STAT5A信号传导	间充质干细胞	降低MI后不良重建	[42]
miR-206	大鼠	靶向Pim-1激酶	间充质干细胞	刺激细胞循环并增强体内心脏再生	[43]
miR-532	小鼠	调节miR-532-prss23轴	内皮-间质转化（EndMT）	减少EndMT，增加内皮细胞增值及新生血管的密度	[44]

miRNA	研究对象	信号通路及靶点	作用细胞	效应机制	引文
miR-320	大鼠	靶向ASK1-JNK / p38通路，抑制IGF-1	心肌细胞	抑制凋亡	[45]
miR-181b	大鼠	靶向AKT3和PI3KR3	心肌细胞	抑制凋亡	[46]
miR-22	大鼠H9c2细胞	调节PI3K / AKT和JAK1 / STAT3途径。	心肌细胞	抗凋亡及抑制心肌纤维化	[47]
miR-20a	大鼠	靶向调节促凋亡因子Egln3/PHD3	心肌细胞	抑制心肌细胞凋亡	[48]
miR-320	小鼠	靶向热休克蛋白20	心肌细胞	抑制心肌细胞凋亡	[49]
miR-140	小鼠	靶向线粒体蛋白1 （Mfn1）	心肌细胞	抑制心肌细胞凋亡	[50]
miR-92a	心梗患者血清	抑制PUMA，PTEN，Bax及caspase 7表达	心肌细胞内皮细胞	促血管生成作用及抗炎症反应	[51]
miR-181a	HEK293细胞，成肌L6细胞和H9c2细胞	靶向谷胱甘肽过氧化物酶-1 （GPx1）	心肌细胞内线粒体	抑制线粒体凋亡	[52]
miR-122	Pax-8基因敲除小鼠	调节CCK-8的表达和Caspase-3的活性	心肌细胞	抑制心肌细胞凋亡	[53]
miR-150	大鼠	靶向c-myb基因	心肌细胞	抑制心肌细胞凋亡	[54]
miR-375	小鼠	调节3-磷酸肌醇依赖性蛋白激酶-1（PDK-1）的表达及激活PDK-1介导的PI3/ AKT信号传导的	骨髓衍生祖细胞	增强BMPAC增殖和形成并抑制细胞凋亡	[55]

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