Table 1. Select cell type–specific miRNA therapies in the treatment of MI.
Complete list of miRNAs reviewed in table S1. IRI, ischemia-reperfusion injury; AngII, angiotensin II; TAC, transverse aortic constriction; IV, intravenous; IM, intramyocardial; IP, intraperitoneal; I. Ventr, intraventricular; EV, extracellular vesicle; Transf, transfection; Lenti, lentiviral; EndMT, endothelial-to-mesenchymal transition; Mito, mitochondrial; ROS, reactive oxygen species.
| miRNA | Effect | Injury model | Delivery method | Target process | Target pathway | Target molecule | Clinical application | Reference |
|---|---|---|---|---|---|---|---|---|
| Cardiomyocytes | ||||||||
|
| ||||||||
| miR-1 | Harmful | In vivo IRI | IV | Apoptosis | PKC apoptosis | PKCε | ** | (43) |
|
| ||||||||
| miR-9 | Harmful | In vivo ischemia | IM | Proliferation | FSTL | FSTL | *** | (73) |
|
| ||||||||
| miR-22 | Harmful | In vivo ischemia | IP | Autophagy | Autophagy | PPARα | *** | (59) |
|
| ||||||||
| miR-302/367 | Beneficial | In vivo ischemia | IV | Proliferation | Hippo-YAP | MST1 | *** | (69) |
|
| ||||||||
| miR-762 | Harmful | In vivo IRI | IV | Apoptosis | ROS production | ND2 | *** | (49) |
|
| ||||||||
| miR-873 | Beneficial | In vivo IRI | IV | Necrosis | Necroptosis | RIPK1/RIPK3 | *** | (53) |
|
| ||||||||
| Let-7a | Beneficial | In vivo AngII | I. Ventr. | Hypertrophy | Undefined | CaM | *** | (80) |
| Cardiac fibroblasts | ||||||||
|
| ||||||||
| miR-21 | Harmful | In vivo ischemia | IM | Fibrosis | ERK/MAPK | SPRY1 | *** | (112) |
|
| ||||||||
| miR-21 | Harmful | In vivo TAC | IV | Apoptosis | ERK/MAPK | SPRY1 | *** | (111) |
|
| ||||||||
| miR-92a | Harmful | In vitro TGF-β | EV | Fibrosis | TGF-β | SMAD7 | * | (106) |
|
| ||||||||
| miR-101 | Beneficial | In vivo ischemia | I. Ventr. | Fibrosis | TGF-β | cFOS | *** | (96) |
|
| ||||||||
| miR-155 | Beneficial | In vivo genetic | NA | Proliferation | RAS | SOS1 | ** | (178) |
| Endothelial cells | ||||||||
|
| ||||||||
| miR-32 | Harmful | In vitro | Transf. | Proliferation | Undefined | KLF2 | * | (228) |
|
| ||||||||
| miR-155 | Harmful | In vivo ischemia | IM | Angiogenesis | AMPK | RAC1 | *** | (142) |
|
| ||||||||
| miR-324 | Beneficial | In vitro H2O2 | Transf. | Apoptosis | Mitofission | MtFR1 (indirect) | * | (135) |
|
| ||||||||
| miR-532 | Beneficial | In vivo ischemia | IM | Angiogenesis | EndMT | PRSS23 | *** | (151) |
| Inflammatory cells | ||||||||
|
| ||||||||
| miR-24 | Beneficial | In vivo ischemia | EV | Inflammatory infiltration | Intrinsic pathway | BIM | *** | (161) |
|
| ||||||||
| miR-155 | Harmful | In vivo ischemia | IV | Inflammatory activation | NF-κB | SOCS1 | *** | (175) |
|
| ||||||||
| miR-182 | Beneficial | In vivo IRI | EV | Inflammatory resolution | PI3k/AKT/mTOR | TLR4 | ** | (162) |
|
| ||||||||
| miR-224 | Beneficial | In vivo ischemia | Lenti. | Inflammatory activation | TGF-β | Undefined | * | (157) |
*
Indicates therapeutic efficacy in in vitro cell-based models.
**
Indicates therapeutic efficacy in in vitro and in vivo models with target pathway identification and characterization.
***
Indicates therapeutic efficacy in multiple model systems and well-defined mechanisms of action including comprehensively validated direct targets.