Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction
Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction
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miR-19a/19b 在心脏再生和心肌梗死保护中的治疗作用
DOI：
10.1038/s41467-019-09530-1
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发表时间：
2019-04-17
影响因子：
16.6
通讯作者：
Wang, Da-Zhi
中科院分区：
文献类型：
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作者：
Gao, Feng;Kataoka, Masaharu;Wang, Da-Zhi
心力衰竭的主要原因是在患病的成人心脏心肌细胞的损失。之前，我们报道了miR-17-92簇在心肌细胞增殖中起关键作用。在这里，我们报道miR-17-92簇成员miR-19a/19b的表达在心力衰竭患者中被诱导。研究表明，在心肌梗死（MI）损伤后，心脏内注射miR-19a/19b模拟物可增强心肌细胞增殖并刺激心脏再生。miR-19a/19b在两个不同的阶段保护成人心脏：心肌梗死后立即的早期阶段和长期保护。全基因组转录组分析表明，与免疫应答相关的基因被miR-19a/19b抑制。使用腺相关病毒方法，我们验证了miR-19a/19b减少mi诱导的心脏损伤并保护心功能。最后，我们通过将miR-19a/19b系统递送至心肌梗死后小鼠体内，证实了miR-19a/19b在保护心功能方面的治疗潜力。我们的研究确立了miR-19a/19b作为治疗心力衰竭的潜在治疗靶点。
The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart failure patients. We show that intra-cardiac injection of miR-19a/19b mimics enhances cardiomyocyte proliferation and stimulates cardiac regeneration in response to myocardial infarction (MI) injury. miR-19a/19b protected the adult heart in two distinctive phases: an early phase immediately after MI and long-term protection. Genome-wide transcriptome analysis demonstrates that genes related to the immune response are repressed by miR-19a/19b. Using an adeno-associated virus approach, we validate that miR-19a/19b reduces MI-induced cardiac damage and protects cardiac function. Finally, we confirm the therapeutic potential of miR-19a/19b in protecting cardiac function by systemically delivering miR-19a/19b into mice post-MI. Our study establishes miR-19a/19b as potential therapeutic targets to treat heart failure.