Table 2.
Role of miR-1 and miR-21 in cardioprotection.
| Type of Intervention | miR | Findings | Reference |
|---|---|---|---|
| Ischemic conditioning | miR-1 | ↑miR-1 in heart tissue after IPostC in rats | [158] |
| ↓miR-1 in plasma after IPostC in pigs | [159] | ||
| ↓miR-1 in right atria after IPostC in human patients undergoing cardiac surgery | [160] | ||
| ↓miR-1 in heart tissue after RIPC in rats | [157] | ||
| ↓miR-1 by RIPC in in vivo cardiac I/R model in rats | [163] | ||
| RIPC prevented up-regulation of miR-1 in right atria and preserved mitochondrial respiration during heart surgery in humans | [162] | ||
| ↓miR-1 by RIPerC during heart surgery in humans | [164] | ||
| miR-21 | ↑miR-21 in heart tissue after IPC and IPostC in animal models and humans | [83,160,161] | |
| knockdown of miR-21 abolished cardioprotective effects of IPost in mice | [161] | ||
| knockdown of cardiac miR-21 abolished IPC-mediated cardioprotection against I/R in rats | [83] | ||
| Pharmacological | miR-1 | insulin protected against miR-1-mediated H2O2-induced injury in H9c2 cells | [175] |
| miR-21 | isoflurane-induced up-regulation of miR-21 associated with ↓PDCD4 protected cardiomyocytes against H2O2 injury | [166] | |
| isoflurane protected mouse hearts exposed to I/R via miR-21 and Akt/NOS/mPTP | [167] | ||
| trimetazidine-induced ↑miR-21 accompanied by cardioprotection against I/R, ↑p-Akt and ↑Bcl-2/Bax in rats. Cardioprotection reversed by anti-miR-21 | [169] | ||
| miR-21 enhanced protective effect of loperamide against H/R injury in rat cardiomyocytes associated with ↓ROS and ↓apoptosis | [170] | ||
| Non-pharmacological | miR-1 | down-regulation of miR-1 by traditional Chinese medicine Tanshinone IIA led to cardioprotection via inhibition of I/R-induced p-38 MAPK in rats | [173] |
| phenolic compound paeonol exerts cardioprotection against epirubicin-induced heart injury via regulation of miR-1, PI3K/AKT/mTOR and NF-κB | [176] | ||
| miR-21 | resveratrol-induced up-regulation of miR-21 associated with protection against I/R in rats | [168] | |
| miR transfection and delivery | miR-21 | adenovirus miR-21 transfection decreased IS via targeting PDCD4/AP-1 | [62] |
| adenovirus miR-21 transfection improved LV remodeling & ↓apoptosis in cardiac I/R in rats | [67] | ||
| lentivirus miR-21 transfection induced cardioprotection against I/R in mice manifested by ↓IS, ↓fibrosis and ↓apoptosis | [64] | ||
| miR-21 transfection to human cardiomyocytes ↓apoptosis via JNK/p38-MAPK/caspase-3 | [68] | ||
| chemically synthesized exogenous miR-21 reduced IS in mice, miR-21-induced protection was abolished with miR-21 inhibitor co-treatment | [165] | ||
| nanoparticle delivery of miR-21 to cardiac macrophages post-MI promoted angiogenesis, reduced hypertrophy, fibrosis, and apoptosis in the remote myocardium | [75] | ||
| miR-21 pretreatment exerted cardioprotection against CVB3 infection via targeting MAP2K3/p38-MAPK in mice | [172] | ||
| Exosomal miR | miR-21 | depletion of exosomal miR-21 reduced protective effect of conditioned medium in H2O2-induced oxidative stress in cardiomyocytes, and in rat hearts exposed to AMI | [69] |
| ↑miR-21 in CPC-derived exosomes prevented apoptosis in H9c2 cells via ↓PDCD4 | [70] |
Abbreviations: I/R: ischemia/reperfusion; H/R: hypoxia/reoxygenation; AMI/MI: (acute) myocardial infarction; PDCD4: programmed cell death protein 4; AP-1: activator protein 1 (downstream molecule of PDCD4); ROS: reactive oxygen species; IS: infarct size; LV: left ventricle; CPC: cardiac progenitor cell; AF: atrial fibrillation; IPC: ischemic preconditioning; IPostC: ischemic postconditioning; RIPC: remote ischemic preconditioning; RIPerC: remote ischemic preconditioning; CVB3: coxsackievirus B3.