Abstract
Aims: Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs). For example, miR-150 is down-regulated in patients with acute myocardial infarction, atrial fibrillation, dilated and ischaemic cardiomyopathy as well as in various mouse heart failure (HF) models. Circulating miR-150 has been recently proposed as a better biomarker of HF than traditional clinical markers such as brain natriuretic peptide. We recently showed using the β-arrestin-biased β-blocker, carvedilol that β-arrestin1-biased β1-adrenergic receptor cardioprotective signalling stimulates the processing of miR-150 in the heart. However, the potential role of miR-150 in ischaemic injury and HF is unknown. Methods and results: Here, we show that genetic deletion of miR-150 in mice causes abnormalities in cardiac structural and functional remodelling after MI. The cardioprotective roles of miR-150 during ischaemic injury were in part attributed to direct repression of the pro-apoptotic genes egr2 (zinc-binding transcription factor induced by ischaemia) and p2x7r (pro-inflammatory ATP receptor) in cardiomyocytes. Conclusion: These findings reveal a pivotal role for miR-150 as a regulator of cardiomyocyte survival during cardiac injury.
Original language | English (US) |
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Pages (from-to) | 387-397 |
Number of pages | 11 |
Journal | Cardiovascular Research |
Volume | 106 |
Issue number | 3 |
DOIs | |
State | Published - Jun 1 2015 |
Keywords
- Apoptotic genes
- Biased G protein-coupled receptor signalling
- Cardioprotection
- β-arrestin
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)