Table 1.
Main findings of the systematic review. The results are divided into columns: author, type of study, miRNAs involved, target (genetic, pathway, cellular), type of regulation (up/down), and clinical consequences. HCM—Hypertrophic cardiomyopathy, MI/R—myocardial ischemic reperfusion, ACS—acute coronary syndrome, MVD—multivessel disease, HF—Heart failure, AF—Atrial fibrillation, CAD—coronary artery disease, DCM—idiopathic dilated cardiomyopathy, CVE—Cardiovascular event, CVD—Cardiovascular disease, ACAS—Asymptomatic carotid artery stenosis, ARVC—Arrhythmogenic right ventricular cardiomyopathy, SCD—Sudden cardiac death, MI—Myocardial infarction, CTEPH—Chronic thromboembolic pulmonary hypertension, FGFR1—Fibroblast growth factor receptor 1.
| First Author, Year, and Country | Study Model | miRNAs Investigated | Biological Sample/Target | Dysregulation (Up/Down) | Effect of Dysregulation |
|---|---|---|---|---|---|
| Bayés-Genis et al., 2018, Spain [23] | Observational prospective study | miR-22-3p, miR-133a-3p, miR-133b, miR-208a-3p, miR-320a, miR-345-5p, MiR-378a-3p, miR-423-5p, miR-499a-5p, MiR-622, miR-1254, MiR-1306-5p | Serum/CCAR1 (cell division and apoptosis regulator protein 1) | up (miR-1254, miR-1306-5p) | Significantly associated with increased in-hospital heart failure (HF) death. |
| Guo et al., 2018, China [24] | Case-control | miR-133a, miR-221 | Plasma/Heart Failure with Reduced Ejection Fraction (HFrEF) gene | down | HF diagnostic biomarkers in elderly patients |
| Masson et al., 2018, Italy [25] | Randomized clinical trial | miR-132 | Plasma/anti-hypertrophic transcription factor FoxO3 | down | Prediction of HF severity |
| Li et al., 2019, China [26] | Case-control | miR-208, miR-494, miR-499, miR-1303 | Plasma/PTEN, ROCK1 | down | miR-208, miR-494, miR-499 and miR-1303 can be used as markers of myocardial infarction (MI), however, they do not have a higher value than traditional troponins |
| Liu et al., 2019, China [27] | Cohort | miR-150-3p, miR-197-5p, miR-320a, miR-494-3p, miR-939-5p, miR-1268a, miR-1275, | Plasma/Cardiomyocytes | up | Increase in HF adverse events |
| Mayer et al., 2019, Czech Republic [28] | Observational prospective study | miR-1, miR-19a, miR-21, miR-34a, miR-126, miR-133a, miR-197, miR-208b, miR-214, miR-223, miR-499 | Serum/Inflammatory cells (increased fibrosis and apoptosis) | down (miR-19a) | In patients with carotid artery stenosis (CAS), a low level of miR-19a is an independent risk factor for mortality |
| Pinchi et al., 2019, Italy [29] | Case-control | miR-1-3p, miR-133a-3p, miR-208a-3p, miR-499a-5p, | Heart tissue/Ion channels | down (miR-1, miR-208) up (all in SCD) | Biomarkers of sudden cardiac death (SCD) due to early acute MI |
| Zhang et al., 2019, China [30] | Case-control | miR-155 | Serum/Genes involved in pulmonary fibrosis and CAD (coronary artery disease). | down | Patients with HF after MI have elevated levels of these miRNAs |
| Zhu et al., 2019, China [31] | Retrospective cohort | miR-182-5p miR-5187-5p | Plasma/VEGF (vascular endothelial growth factor). | up | Diagnostic biomarkers for CAD |
| Asulin et al., 2020, Israel [32] | Case-control | miR-145-5p, miR-199a-5p, miR-5701 | Human genes of development, cell growth, differentiation, proliferation, apoptosis, metabolism, and tissue remodeling | up (rheumatic valvulopathy) down (idiopathic valvulopathy) | Useful for differentiating the etiology of rheumatic from idiopathic valvulopathies |
| Barbalata et al., 2020, Romania [33] | Original article | miR-92a-3p miR-142-3p, miR-155-5p, miR-223-3p, | Plasma/TGF-beta2 | (miR-92a) Down (miR-142, miR-155, miR-223) up |
Prediction of CVD in patients with peripheral arterial disease |
| Ben-Zvi et al., 2020, Israel [34] | Case-control | miR-21-5p, miR-92b-3p, miR-125b-5p, miR- 133a-3p | Serum/cardiomyocytes | up (miR-125b-5p, miR-133-3p), down (miR-21-5p, miR-92b-3p) | Increased incidence of HF |
| Elbaz et al., 2020, France [35] | Case-control | miR-16, miR-92a, miR-122, miR-150, miR-186, miR-195, miR-223-5p, | Serum/Inflammatory cells (increased fibrosis and apoptosis) | up | Biomarker risk of ACS (acute coronary syndrome). |
| Ling et al., 2020, China [36] | Case-control | miR-21, miR-126 | Serum/PTEN | (miR-21) down (miR-126) up |
Biomarker of ACS |
| Liu et al., 2020, China [37] | Case-control | miR-1-3p, miR-20b-5p, miR-30b-5p, miR-142-3p, miR-1273g-3p, miR-6515-3p, miR-6793-5p, miR-7109-3p, | Serum/MAPK signaling pathway | up | Involvement in the pathogenesis of angina (stable and unstable) |
| Nie et al., 2020, China [38] | Case-control | miR-4281 miR-4763-3p | Plasma/KEGG related to apoptosis (TGF-β, mTOR, insulin, MAPK, p53) | up | Potential biomarker of fulminant myocarditis |
| Santos et al., 2020, Denmark [39] | Case-control | miR-130b-3p, miR-208a-3p, miR-338-5p | Heart biopsy/ion channel genes, extracellular matrix genes | down (ion channel genes) up (extracellular matrix genes) | Involvement in the development of AF |
| Silverman et al., 2020, USA [40] | Case-control | miR-29a-3p, miR-30a-5p, miR-150-5p | Plasma/Inflammatory cells (increased fibrosis and apoptosis) | up | Risk of increased SCD in patients with CAD |
| Su et al., 2020, China [41] | Case-control | miR-1 | Serum/Endothelial function, angiogenesis and cell apoptosis | up | miR-1 within 3 h of acute chest pain is an independent risk factor for mortality in patients with MI |
| Turky et al., 2020, Egypt [42] | Observational prospective study | miR-133a | Plasma/FGFR1 | up | Biomarker for early identification of stable CAD |
| Wakabayashi, 2020, Japan [43] | Case-control | miR-16-5p, miR-17-5p, miR-92a-3p miR-106a-5p, miR-135a-3p, miR-150-3p, miR-191-5p, mR-320b, miR-451a, miR-486-5p, miR-663b, | Serum/pro-inflammatory cytokines in foam cells and collagen synthesis in vascular smooth muscle cells | up | Increased incidence of ischemic heart disease |
| Wang et al., 2020, China [44] | Case-control | miR-22, miR-499 | Serum/Cardiac myosin heavy chain gene | up | Sensitive and specific biomarkers for the diagnosis of MI |
| Weldy et al., 2020, USA [45] | Observational prospective study | miR-28- 3p, miR-371b-3p, miR-433-3p | Plasma/SMAD3 and 4, TGF-β1 and 2, E2F family transcription factors | up | Increasing right ventricular (RV) size and decreasing RV systolic function |
| Brundin et al., 2021, Sweden [46] | Case-control | miR-16-5p, miR-21-5p, miR-29-5p, miR-133a-3p, miR-191-5p, miR-320a, miR-423-5p | Serum/extracellular matrix proteins | up | Seven miRNAs were upregulated both in subjects suffering from idiopathic dilated cardiomyopathy (DCM) and ischemic heart disease (IHD) |
| Chen et al., 2021, China [47] | Case-control | miR-4329, miR-6718-5p | Plasma/MAPK, PI3K-Akt, Ras, Rap1 signaling pathway | down | Biomarkers for acute MI |
| Coban et al., 2021, Turkey [48] | Original article | miR-18a-3p, miR-130b-5p | Serum/SPP1 and TNFRSF11B genes | up | Biomarkers of CAD development |
| Elgebaly et al., 2021, USA [49] | Case-control | miR-106b miR-137, | Serum/Genes of Nourin | up | Biomarkers for early diagnosis of myocardial ischemia in patients suspected of CAD |
| Garcia-Elias et al., 2021, Spain [50] | Case-control | miR-22-5p, miR-199a-5p | Plasma/L-type Ca2+ channel, NCX and connexin-40 | up | Decreased cardiac ejection fraction and increased incidence of AF |
| Gevaert et al., 2021, Belgium [51] | Observational prospective study | miR-181c | MAPK1, DNM2, and CDH1 (HFpEF pathophysiology) | up | Predicts response to exercise training in patients with HF |
| He et al., 2021, China [52] | Observational prospective study | miR-29b | Plasma/Inflammatory cells (increased fibrosis and apoptosis) | down | Independent risk factor for coronary artery calcification in patients with renal disease |
| Hromadka et al., 2021, Czech Republic [53] | Randomized clinical trial | miR-126-3p, miR-223-3p | VEGF, VCAM-1, SPRED1, PIK3R2/p85- beta, P2Y12, RPS6KB1/HIF1a | up | Independent risk stratification biomarkers for thrombotic events after MI |
| Lu et al., 2021, China [54] | Observational prospective study | miR-27b | Serum/Vascular smooth muscle cells |
up | Prediction of the occurrence of ACS |
| Mihaleva et al., 2021, Bulgaria [55] | Case-control | miR-16-5p, miR-155-3p, miR-155-5p, miR-210, miR-221-3p, miR-424-5p | Serum/HIF1A (transcriptional regulator of the adaptive response to hypoxia) | up | Biomarker of cardiovascular complications in diabetic patients |
| Moric-Janiszewska et al., 2021, Poland [56] | Case-control | miR-1, miR-133a, miR-133b | Genes involved in the regulation of ion channels | up | Diagnostic biomarkers of arrhythmia in pediatric patient |
| Neiburga et al., 2021, China [57] | Original article | miR-10-5p, miR-10b-3p, miR-17-3p, miR-21-5p, miR-151a-5p, miR-181a-5p, miR-185-5p, miR-194-5p, miR-199a-3p, miR-199b-3p, miR-212-3p, miR-363-3p, miR-548d-5p, miR-744-5p, miR-3117-3p, miR-5683, miR-5701 | Serum/AKT, PTEN and IRS1 | down | Biomarkers of CVD |
| Sacchetto et al., 2021, Italy [58] | Case-control | miR-185-5p | Plasma/Inflammatory cells | up | Diagnostic biomarkers for ARVC (arrhythmogenic right ventricular cardiomyopathy) |
| Shen et al., 2021, China [59] | Case-control | Let-7b-3p, miR-21-3p, miR-28-3p, miR-99b-5p, miR-181c-3p, miR-133b, miR-320a, miR-500a-3p, miR-574-5p, miR-940, miR-1268b, miR-1307-3p, miR-4286, miR-4485-3p, | Serum/PI3K/AKT pathway | up (miR-4286) | Biomarker for increased risk of ACS |
| Suzuki, 2021, Japan [60] | Case-control | miR-126, miR-221, miR-222 | Serum/NF-κB pathway | down | Increased incidence of hypertension |
| Szelenberger et al., 2021, Poland [61] | Case-control | miR-130b-3p, miR-142-3p, miR-146a-3p, miR-197-5p, miR-301a-3p, miR-338-3p, miR-3162-5p, miR-3656, miR-4299, miR-8069 | Platelet/ARHGEF12, (regulation of actin cytoskeleton), AKT3 (focal adhesion), ARHGEF12 (vascular smooth muscle contraction) | 5 miRNAs were upregulated (miR-301a-3p, miR-142-3p, miR-146a-3p, miR-130b-3p, miR-338-3p) and 5 miRNAs were downregulated (miR-8069, miR-4299, miR-3656, miR-197-5p, miR-3162-5p) | Potential platelet biomarker of ACS |
| Thottakara, 2021, Germany [62] | Case-control | miR-1, miR-495-3p, miR-499a-5p, miR-627-3p, miR-3144, miR-4454, | Plasma/Sarcomeric genes | up | Increased incidence of hypertrophic cardiomyopathy (HCM) |
| Tong et al., 2021, China [63] | Observational prospective study | miR-222 | Serum/PI3K/AKT pathway | down | Increased incidence of MI/R |
| Xiao et al., 2021, China [64] | Case-control | miR-146a | Serum/S100A12 | up | Biomarker for adverse prognosis of ST-Segment Elevation MI |
| Yamada et al., 2021, Japan [65] | Retrospective cohort | miR-21, miR-29a, miR-126 | Serum/Inflammatory cells | up (miR-21 and miR-19a) down (miR-126) |
Risk of premature death from cancer and CVD |
| Yan et al., 2021, China [66] | Case-control | miR-133a-3p, miR-223-3p, miR-499a-5p, miR-3113-5p, | Heart tissue/Inflammatory cells (increased fibrosis and apoptosis) | up | Sensitive biomarkers of SCD |
| Zhelankin et al., 2021, Russia [67] | Case-control | miR-21-5p, miR-17-5p, miR-146a-5p, | Plasma/cardiomyocytes | up (miR-21-5p, miR-146a-5p) down (miR-17-5p) | An increase in miR-146a-5p and miR-21-5p is an indicator of ACS, a decrease in miR-17-5p could be considered a general biomarker of CAD. |
| Eikelis et al., 2022, Australia [68] | Original article | miR-132 | Serum/PTEN, SIRT1 | down | Biomarker of hypertension in obese patients |
| Eyyupkoca et al., 2022, Turkey [69] | Case-control | miR-23b-3p, miR-26b-5p, miR-199a-5p, miR-301a-3p, miR-374a-5p, miR-423-5p, miR-483-5p, miR-652-3p | Plasma/Gene expression and remodeling of extracellular matrix | down (miR-301a-3p, miR-374a-5p) up (miR-423-5p) | Biomarker of adverse left ventricular remodeling after MI |
| Gager, 2022, Austria [70] | Observational prospective study | miR-125a (miR-125b, miR-223) |
Plasma/Cardiomyocytes | up | Reduction of survival for ACS |
| James et al., 2022, Sweden [71] | Case-control | miR-224-5p | Extracellular Vesicles (EVs)/SMAD unit (TGF-beta pathway) | up | Biomarker of endothelial dysfunction in patients with low coronary flow reserve |
| J. Li et al., 2022, China [72] | Case-control | miR-203 | Serum/Inflammatory cells (increased fibrosis and apoptosis) | up | Biomarker for early prediction of ST-Segment Elevation MI |
| Miao et al., 2022, China [73] | Retrospective study | miR-17-5p, miR-20a-5p, miR-93-5p, miR-665, miR-3202 | Serum/Pulmonary artery smooth muscle cells and pulmonary artery endothelial cells (proliferation and apoptosis) | miR-20a-5p, miR-93-5p, miR-17-5p downregulated | Useful parameter in the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) |
| Mompeón et al., 2022, Spain [74] | Observational prospective study | let-7g-5p, let-7e-5p, miR-26a-5p | Plasma/Involvement in the production of cytokines and chemokines | down | Potential biomarker of MI prognosis |
| Moscoso et al., 2022, Spain [75] | Observational prospective study | miR-125b, miR-499a, | Serum/KEGG related to apoptosis (TGF-β, mTOR, insulin, MAPK, p53) | up | Improvement of left ventricular ejection fraction after cardiac resynchronization therapy |
| de los Reyes-García et al., 2022, Spain [76] | Original article | miR-146a | Serum/TLR/NF-kB pathway | down | Contribution to thrombo-inflammation and MI recurrence in young patients |
| Wang et al., 2022, China [77] | Observational prospective study | miR-29 | Serum/PI3K/mTOR/HIF1α/VEGF pathway | down | Development of MI |
| Yang et al., 2022, China [78] | Case-control | miR-29b (miR-let-7b) |
Serum/Osteogenic transcription factors | down | Increased incidence of coronary artery calcification |
| Yu et al., 2022, China [79] | Case-control | miR-221, miR-222 | Plasma/c-Raf/MEK/ERK pathway | up | Severity of ACS |
| Zhang et al., 2022, China [80] | Case-control | miR-21, miR-208b | Plasma/TGF-β1/Smad-3 Signaling Pathway | up | Cardiac fibrosis progression through activation of the TGF-β1/Smad-3 signaling pathway |
| Zhou et al., 2022, China [81] | Observational prospective study | miR-133a | Serum/FGFR1 | up | Biomarker for early identification of stable CAD |