Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction.
Feng GaoMasaharu KataokaNing LiuTian LiangZhan-Peng HuangFei GuJian DingJianming LiuFeng ZhangQing MaYingchao WangMingming ZhangXiaoyun HuJan KyselovicXinyang HuWilliam T PuJian'an WangJinghai ChenDa-Zhi WangPublished in: Nature communications (2019)
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.
Keyphrases
- cell proliferation
- long non coding rna
- heart failure
- long noncoding rna
- left ventricular
- poor prognosis
- immune response
- genome wide
- stem cells
- high glucose
- signaling pathway
- type diabetes
- dna methylation
- oxidative stress
- angiotensin ii
- transcription factor
- skeletal muscle
- endothelial cells
- ultrasound guided
- wound healing