MicroRNA profiling unveils hyperglycaemic memory in the diabetic heart
MicroRNA profiling unveils hyperglycaemic memory in the diabetic heart
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DOI：
10.1093/eurheartj/ehv599
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发表时间：
2016-02-07
影响因子：
39.3
通讯作者：
Cosentino, Francesco
中科院分区：
文献类型：
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作者：
Costantino, Sarah;Paneni, Francesco;Cosentino, Francesco
最近的随机试验表明，强化血糖控制不能减少糖尿病患者的心力衰竭相关事件。尽管恢复了正常血流量，但持续性心肌损伤的分子线索仍然难以捉摸。MicroRNA（miRNAs）是一类小的非编码RNA，参与心脏重构的转录调控。本研究调查是否参与高血压记忆在diabetic heart.Methods和结果miRNA景观进行了评估小鼠miRNome miRNA PCR阵列在左心室标本收集4个月大的链脲佐菌素诱导的糖尿病小鼠，或没有密集的血糖控制缓释胰岛素植入物。与对照组相比，在糖尿病心脏中观察到1008个总miRNAs中的316个失调。其中，209个上调，107个下调>2.0倍。有趣的是，即使在随后的正常血糖后，这些miRNAs中的268种表达在糖尿病小鼠中仍然显著改变。免疫途径分析显示，失调的miRNAs参与了心肌细胞凋亡的信号网络（miR-320 b、miR-378、miR-34 a）、纤维化（miR-125 b、miR-150、miR-199 a、miR-29 b、miR 30 a），肥大性生长（miR-1，miR-150，miR-199a，miR-133a，miR-214，miR-29a，miR-125b，miR-221，miR-212），自噬（miR-133 a，miR-221，miR-212，miR 30 a），氧化应激（miR-221、miR-146 a、miR-34 a、miR-210、miR-19 b、miR-125 b、miR-27 a、miR-155）与心力衰竭结论血糖控制不能挽救糖尿病心脏中高血糖诱导的miRNA景观改变。这些发现可能提供新的见解，以了解为什么糖尿病心肌病的进展，尽管血糖水平正常化。
Aims Recent randomized trials suggest that intensive glycaemic control fails to reduce heart failure-related events in patients with diabetes. The molecular cues underlying persistent myocardial damage despite normoglycaemia restoration remain elusive. MicroRNAs (miRNAs), a class of small non-coding RNAs, orchestrate transcriptional programs implicated in adverse cardiac remodelling. The present study investigates whether miRNAs participate to hyperglycaemic memory in the diabetic heart.Methods and results miRNA landscape was assessed by Mouse miRNome miRNA PCR Arrays in left ventricular specimens collected from 4-month-old streptozotocin-induced diabetic mice, with or without intensive glycaemic control by slow-release insulin implants. A dysregulation of 316 out of 1008 total miRNAs was observed in the diabetic hearts when compared with controls. Of these, 209 were up-regulated and 107 were down-regulated by >2.0-fold. Interestingly enough, the expression of 268 of those miRNAs remained significantly altered in diabetic mice even after subsequent normoglycaemia. Ingenuity pathway analysis revealed that dysregulated miRNAs were implicated in myocardial signalling networks triggering apoptosis (miR-320b, miR-378, miR-34a), fibrosis (miR-125b, miR-150, miR-199a, miR-29b, miR30a), hypertrophic growth (miR-1, miR-150, miR-199a, miR-133a, miR-214, miR-29a, miR-125b, miR-221, miR-212), autophagy (miR-133a, miR-221, miR-212, miR30a), oxidative stress (miR-221, miR-146a, miR-34a, miR-210, miR-19b, miR125b, miR27a, miR-155), and heart failure (miR-423, miR-499, miR-199a), respectively.Conclusions Glycaemic control is not able to rescue hyperglycaemia-induced alterations of miRNA landscape in the diabetic heart. These findings may provide novel insights to understand why diabetic cardiomyopathy progresses despite normalization of blood glucose levels.