TABLE 1.
Summarizes a selection of miRNAs that have been identified with either a harmful or cardioprotective property in cardiovascular disease.
| miRNA | Disease model | Releasing cell type | Experimental approach | Experimental model | Effect | Identified targets | Recipient cell | Off-target effects | PMID |
| miR-665 | I/R | CM | Suppression of miR-665 via dexmedetomidine | Rat heart Langendorff preparation | Improved LVDP during reperfusion | AK1, Cbr2 | Cardiac cells | Not investigated | 31026731 |
| HF | – | I.m. injection with anti-sense miRNA plasmids | Rat model of HF | Improved LVEF, reduced CM apoptosis, improved Mc ultrastructure | GLP1R | Cardiac cells | Not investigated | 30666648 | |
| HF | Global | I.v. injection of rAAV miR-665 inhb. | Murine model of LV pressure overload | Improved LVEF, reduced fibrosis, improved vascularization | CD34 | Global | Not investigated | 30243022 | |
| – | Human CM | In vitro gain and loss of function in human CM | Mechanistic model | – | Cbr1 and Cbr2 | Human CM | – | 25111814 | |
| miR-132 | I/R | – | Loss of function in vivo, gain of function in vitro | Murine hind limb ischemia | Slower perfusion recovery, less collateralization, modulation of RAS-MAPK signaling | Rasa1 and Spred1 | – | Not investigated | 25016614 |
| Afib | – | In vitro loss and gain of function in CF | Mechanistic model | In human and dog with Afib decreased expr. miR-132 in atrium | CTGF | CF | – | 28731126 | |
| DCM | – | In vitro analysis of cardiac cell isolates from DCM rats, overexpression of miR-132 | DCM rat model | Activation of PI3K/Akt pathway, CM apoptosis down | PTEN | – | – | 30271437 | |
| AMI | BM-MSCex electroporated with miR-132 | I.m. injections with MSCex | Murine model of AMI | Increased LVEF, enhanced neovascularization in BZ | Rasa1 | HUVECS | Not investigated | 30216493 | |
| miR-132 + miR-126 | DMap | – | Transfection of aortic rings with miR-132, miR-126 | Endothelial sprouting in aortic rings under high glucose | Decreased EC apoptosis, improved endothelial sprouting | Spred1 | HUVECS, Ecs | – | 31179325 |
| miR-210 + miR-132 + miR-146a-3p | AMI | CPCs | I.v. injection with CPCex rich in miR-210, miR-132, miR-146a-3p vs. Fibex | Murine model of AMI | Less CM apoptosis, enhanced angiogenesis in BZ, improved LVEF | EFNA3, PTP1b | – | Not investigated | 28731126 |
| miR-126 | AMI | AT-MSCs overexpressing miR-126 | I.m. injection of AT-MSCex | Murine model of AMI | Increased neoangiogenesis | Not investigated | – | Not investigated | 29241208 |
| miR-126-5p | Endothelial injury | – | KO of EC Dicer and rescue experiment with miR-126-5p transfection | CA injury | Endothelial Dicer processes pre-mir-126 into mir-126-3p (guide strand) and the passenger strand-5p. 5p is involved in dendothelial repair and proliferation by targeting the Notch1 inhibitor Delta-like homolog 1 (Dlk1) | Dlk1 | ECs | Not investigated | 30213595 |
| mir-210 | AMI | – | Observational study | AMI in rats | Increased levels of miR-210 | – | – | – | 31596148 |
| AMI | BM-MSCs | BM-MSCs rich in miR-210 vs. BM-MSCs with miR-210 silencing | Murine model of myocardial infarction | Increase LVEF, increased neoangiogenesis | EFNA3 | – | Not investigated | 28249798 | |
| I/R | BM-EPCs | BM-EPCs gain and loss of miR-210 | Murine hind limb ischemia | With miR-210 improved perfusion recovery and collateralization | EFNA3 | ECs | Not investigated | 29908843 | |
| I/R | – | Loss and gain of function | In vitro in H9c2 cells, mechanistic model | CXCR4 | H9c2 | – | 29710553 | ||
| mir-206 | Afib | Lentiviral overexpression of miR-206 in PVFP | Canine model of Afib | Overexpression of miR-206 increased incidence of Afib | GCH1 | – | Not investigated | 29436714 | |
| Afib | – | Overexpression of miR-206 in murine hearts | Transgenic mouse model | Overexpression led to decreased lifespan and arrhythmias | Cx43 | – | Not investigated | 30322759 | |
| AMI | – | Cardiac specific expression of miR-206 | Murine model of AMI | CM hypertrophy and increases survival under AMI | FBPP1 | – | Not investigated | 26333362 | |
| HF | – | Increased expression of miR-206 via HMGB1 | Murine model of AMI | Increased collagenolytic activity, decreases myocardial fibrosis | TIMP3 | CF | Not investigated | 21731608 | |
| AMI | – | In vitro loss and gain of function, with in vivo confirmation | Murine model of AMI | Reduced CM apoptosis, improved LVEF | ATG3 | H9c2 | Not investigated | 30551524 | |
| miR-206 + miR-216b | AMI | – | Via HDC gain and loss influence expression of miR-206, miR-216b | Murine model of AMI | Targets Atg13 and reduces autophagy upon hypoxia. miR-206 is induced via histamine | ATG3 | – | Not investigated | 29880830 |
| miR-206 + miR-1 | DMap | – | In vitro loss and gain of function | In vitro in H9c2 cells, mechanistic model | Increased CM apoptosis | Hsp60 | H9c2 | – | 20655308 |
| miR-146a | DCM | CF, CM | AAV9 mediated overexpression of miR146a in vivo and in vitro | Murine model of LV pressure overload | Decreased myocardial contractility | SUMO1 | CM | Not investigated | 30355233 |
| AMI | EPCs | EPC injection in BZ | AMI in rats | Downregulation of miR-146a and reduced CM apoptosis and increased VEGF expression | – | – | Not investigated | 30344699 | |
| – | – | Lentiviral overexpression of miR-146a in H92c | In vitro in H9c2 cells, mechanistic model | Increases MMP9, may reduce fibrosis in injured heart | FOS, AP1 | CM | – | 26112171 | |
| Sepsis induced cardiac dysfunction | – | Transfection of mice with miR-146a, in vitro H9c2 and macrophages | Murine sepsis model | Attenuation of sepsis induced myocardial dysfunction | IRAK, TRAF6 | H9c2, J774 macrophages | 26048146 | ||
| DoxDCM | CM | In vitro overexpression and suppression of miR-146a | In vitro in H9c2 cells, mechanistic model | Induction of cell death upon Dox treatment | ErbB4 | H9c2 | – | 20495188 | |
| AMI | AT-MSCs overexpressing miR-146a | I.m. injections of AT-MSCex native and overexpressing miR-146a | AMI in rats | Decreased CM apoptosis, decreased inflammation, decreased fibrosis | EGR1 | H9c2 | Not investigated | 30362610 | |
| miR-146a-5p | DoxDCM | CPCs | CPCex rich in miR-146a-5p vs. Fibex | DoxDCM model in rats | Decreased CM apoptosis | Traf6, Smad4, Nox4, Mpo | – | Not investigated | 31098627 |
| miR-146a + miR-155 | – | DC | Injection of endotoxin exposed mice with Dcex rich in miR-155 and miR-146a | Murine model of endotoxin inflammation | miR-146a attenuates inflammation, miR-155 increases inflammation | – | – | Not investigated | 26084661 |
| miR-22 | AMI | – | AAV9 overexpression of miR-22 | AMI in rats | Decreased CM apoptosis, decreases infarct size | CBP | – | Not investigated | 24338162 |
| – | – | Overexpression of miR-22 in murine lungs, zebrafish and ECs in vitro | – | VEC | EC | Not investigated | 28112401 | ||
| AMI, HF | – | Gain and loss study on miR-22 | In vitro in CF, mechanistic model | Overexpression limits expression of Col1α1, Col3α1 | TGFβR | CF | – | 27997889 | |
| AMI | – | Gain and loss study on miR-22 | In vitro in rat CMs | Overexpression prevented autophagy and apoptosis in CMs | p38α | CM | – | ||
| AMI | – | I.m. injection of miR-22 inhib., loss and gain function in vitro | AMI in rats | Inhibition decreases infarct size, reduces CM apoptosis | Sirt1, PGC1α | H9c2 | Not investigated | 27174562 | |
| DCM | – | miR-22 deficient mice and gain and loss function in H9c2 | Murine model of left ventricular pressure over load | miR-22 suppression led to left ventricular dilation | PReBPb | H9c2 | Not investigated | 22570371 | |
| DCM | – | Gain and loss of miR-22 in mice | Murine model of left ventricular pressure overload | Overexpression of miR-22 protected from DCM | Sirt1, Hdac4 | – | Not investigated | 23524588 | |
| – | – | Gain and loss study in H9c2 | In vitro in H9c2 cells, mechanistic model | Prevents the activation of NFkB/Caspase3 mediated apoptosis upon stress | p65 | H9c2 | – | 30504734 | |
| AMI | – | In vitro gain and loss study, in vivo miR-22 KO mice | Murine model of AMI | In miR-21 KO mice decreased survival, decreased LVEF, increased scar size | KBTBD7 | Macrophages | 29991775 | ||
| miR-21 | AMI | – | AAV9 overexpression of miR-21 | AMI in rats | Promotes cardiac fibroblast activation and CF to myofibroblast transformation (CMT) | Jagged1 | – | Not investigated | 29808534 |
| – | Targets PDCD4 to reduce apoptosis after HIF-1alpha activated expression of mir21 | 29170412 | |||||||
| AMI | – | In vitro in CF, in vivo induction of miR-21 via TGF-β1 | Murine model of AMI | Increased fibrosis in the heart upon AMI | Smad7 | CF | Not investigated | 28817807 | |
| – | – | Gain and loss study in H9c2 cells | In vitro in H9c2 cells, mechanistic model | Inhibits autophagy and apoptosis upon I/R partially via the Akt/mTOR pathway | – | H9c2 | – | 27680680 | |
| – | – | Exposure of H9c2 cells with CPC derived EVs rich in miR-21 | In vitro in H9c2 cells, mechanistic model | Targets PDCD4 when CDC derived exosomes are added to CMs | – | H9c2 | – | 27336721 | |
| – | – | Gain and loss study in PBMCs | In vitro in human PBMCs, mechanistic model | Via targeting SMAD7, mir-21 can reduce the number of circulating Tregs | Smad7 | Human Tregs | – | 26383248 | |
| – | – | Gain and loss study in H9c2 cells | In vitro in H9c2 cells, mechanistic model | Proof for a positive feedback loop between mir-21 and HIF-1alpha which reduces apoptosis upon hypoxia and stress | PTEN | H9c2 | – | 24983504 | |
| miR-21-5p | – | – | Gain and loss study in H9c2 | In vitro in H9c2 cells, mechanistic model | Modulation of reliance on glycolytic or fatty acid oxidation in mitochondria | – | H9c2 | – | 30657727 |
| – | BM-MSCs | Exposure of H9c2 cells with BM-MSCex rich in miR-21a-5p | In vitro in H9c2 cells, mechanistic model | Reduction of CM apoptosis upon stress. This was identified in EVs from MSCs (miR-21a-5p). | PDCD4, PTEN, Peli1 an dFasL | H9c2 | – | 29698635 |
AAV, adeno-associated-virus; Afib, atrial fibrillation; AMI, acute myocardial infarction; AT-MSCex, AT-MSC exosomes; AT-MSCs, adipose tissue derived mesenchymal stem cells; BM-EPCs, bone marrow derived endothelial progenitor cells; BM-MSCex, BM-MSC exosomes; BM-MSCs, bone marrow derived mesenchymal stem cells; CF, cardiac fibroblast; CPCs, cardiac progenitor cells; DCex, dendritic cell exosomes; DCM, dilated cardiomyopathy; DCs, dendritic cells; DMap, diabetic myocardial microangiopathy; DoxDCM, doxorubicin induced dilated cardiomyopathy; ECs, endothelial cells; EPCs, endothelial progenitor cells; HF, heart failure; HUVECs, human umbilical vein endothelial cells; I/R, ischemia reperfusion.