Modulation of apoptosis-related microRNAs following myocardial infarction in fat-1 transgenic mice vs wild-type mice
Modulation of apoptosis-related microRNAs following myocardial infarction in fat-1 transgenic mice vs wild-type mice
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DOI：
10.1111/jcmm.13846
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发表时间：
2018-11-01
影响因子：
5.3
通讯作者：
Wang, Lei
中科院分区：
文献类型：
--
作者：
Ma, Huan;Chen, Peipei;Wang, Lei
micrornas （miRNAs）转录后调控心肌梗死（MI）后的心脏修复。Omega-3多不饱和脂肪酸（-3 PUFAs）可能支持心肌梗死后的心脏愈合，但其机制尚不清楚。方法结果fat-1转基因小鼠体内表达-3脂肪酸去饱和酶，可将-6 PUFAs转化为-3 PUFAs。采用永久结扎法对fat-1转基因小鼠（n=30）和野生型小鼠（n=30）进行心肌梗死诱导。其他转基因小鼠和WT小鼠分别进行假手术（n=30和n=30）。闭塞后一周，通过超声心动图测量心功能，并使用组织学和miRNA微阵列分析评估梗死面积。所选miRNA的表达用实时荧光定量PCR进行验证。心肌梗死1周后，fat-1转基因心肌的心功能较WT心肌更好，纤维化面积更小，心肌细胞凋亡较少。心肌梗死后分析显示，与WT组相比，脂肪-1组有33个mirna显著上调，35个mirna显著下调（分别为n=3和n=2只小鼠）。在选定的凋亡相关mirna中，与WT小鼠相比，脂肪-1转基因小鼠中有9个mirna上调（miR-101a-3p、miR-128-3p、miR-133a-5p、miR-149-5p、miR-192-5p、miR-1a-3p、miR-208a-3p、miR-29c-5p、miR-30c-2-3p）， 3个mirna下调（miR-210-3p、miR-21a-3p、miR-214-3p）。京都基因和基因组百科全书（KEGG）途径分析表明，这些mirna可能在心肌梗死中发挥作用。此外，与WT心脏相比，在梗死的脂肪-1转基因小鼠心脏中，Bcl-2表达增加，caspase-3表达降低。结论-3 PUFAs可能通过调控心肌细胞凋亡相关mirna和靶基因，对心肌梗死后心肌细胞具有保护作用。
BackgroundmicroRNAs (miRNAs) post-transcriptionally regulate cardiac repair following myocardial infarction (MI). Omega-3 polyunsaturated fatty acid (-3 PUFAs) may support cardiac healing after MI, but the mechanism is unclear.MethodsResultsThe fat-1 transgenic mouse expresses a -3 fatty acid desaturase which converts -6 PUFAs to -3 PUFAs invivo. MI was induced in fat-1 transgenic (n=30) and wild-type (WT) mice (n=30) using permanent ligation. Other transgenic and WT mice underwent sham procedure (n=30 and n=30, respectively). One week after occlusion, cardiac function was measured by echocardiography and the infarct size was assessed using histology and miRNA microarray profiling. Expression of selected miRNA was confirmed using quantitative real-time PCR.One week following MI, the fat-1 transgenic myocardium had better cardiac function, a smaller fibrotic area, and fewer apoptotic cardiomyocytes than WT myocardium. Post-MI profiling showed 33 miRNAs that were significantly up-regulated, and 35 were down-regulated, in fat-1 group compared to the WT group (n=3 and n=2 mice, respectively). Among selected apoptosis-associated miRNAs, 9 miRNAs were up-regulated (miR-101a-3p, miR-128-3p,miR-133a-5p,miR-149-5p,miR-192-5p,miR-1a-3p,miR-208a-3p,miR-29c-5p,miR-30c-2-3p), and 3 were down-regulated (miR-210-3p,miR-21a-3p,miR-214-3p) in fat-1 transgenic mice compared with WT mice. Kyoto encyclopaedia of genes and genomes (KEGG) pathway analysis indicated likely roles for these miRNAs in MI. Furthermore, Bcl-2 expression was increased, and caspase-3 decreased, in infarcted fat-1 transgenic mouse hearts compared to WT hearts.Conclusions-3 PUFAs may have a protective effect on cardiomyocytes following MI through their modulation of apoptosis-related miRNAs and target genes.