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. 2024 Aug 20;15:1399850. doi: 10.3389/fphar.2024.1399850

TABLE 1.

Regulatory role of miRNAs from cardiac cells-derived exosomes in various cell crosstalk.

Donor cells Recipient cells Enriched miRNA Regulatory role References
CMs after MI Normal CMs miR-328-3p miR-328-3p regulates the Caspase signaling pathway and promotes the apoptosis of normal CMs. Huang et al. (2021)
CMs treated with epigallocatechin gallate I/R-induced CMs miR-30a miR-30a inhibits CMs apoptosis and autophagy induced by I/R by increasing the average diameter and concentration of CMs exosomes as well as the expression level of miR-30a mRNA and specific protein in exosomes. Zhang et al. (2020)
Fibrotic CMs Normal FBs miR-208a miR-208a inhibits the expression of DYRK2 in FBs, promotes the dephosphorylation of activated T nuclear factor in the cytoplasm, and then promotes the proliferation of FBs and the transformation into myoblasts. Yang et al. (2018)
Hypoxic CMs FBs miR-208a/b miR-208a/b inhibits the apoptosis of FBs, promotes survival and migration, enhances the accumulation of α-SMA, type I collagen, type III collagen, reactive oxygen species, malonaldehyde, and Fe2+, and inhibits the expression of GPX4, a key regulator of iron death. Guo et al. (2023)
Hypertrophic CMs stimulated by mechanical overstretch for 24 h FBs miR-494-3p miR-494-3p regulates FBs activation by inhibiting PTEN expression and activating the AKT/Smad2/3/ERK signaling pathway and is closely related to the occurrence and development of myocardial fibrosis caused by stress overloading. Tang (2020)
H9c2 transfected with miR-217 mimics FBs miR-217 miR-217 targets PTEN to enhance the proliferation of FBs and participate in cardiac hypertrophy and fibrosis. Nie et al. (2018)
CMs after MI FBs after MI miR-195 miR-195 is significantly upregulated in CMs-derived exosomes and can be transferred to FBs to participate in MFBs activation. Morelli et al. (2019)
CMs treated with H2O2 for 3 h ECs treated with H2O2 for 3 h miR-19a-3p miR-19a-3p inhibits ECs proliferation and tubular formation by down-regulating HIF-1α protein levels, and induces, cell death. Gou et al. (2020)
CMs from Goto-Kakizaki rats ECs miR-320 miR-320 inhibits ECs proliferation, migration, and tubular formation. Wang et al. (2014)
CMs stimulated by phenylephrine and isoproterenol ECs miR-200c-3p miR-200c-3p inhibits ECs proliferation, migration and tubule formation. Ottaviani et al. (2019)
Hypoxic CMs Gli1+ cells miR-223 miR-223 significantly up-regulates the levels of Gli1+ fibrosis-associated protein α-SMA, collagen receptor-discoid domain receptor 2, and type I collagen. Lin et al. (2019)
Angiotensin II-induced CMs Macrophages miR-155 miR-155 induces ERK, JNK, and p38 through the enrichment of miR-155, thereby stimulating the inflammatory response of macrophages. Yu et al. (2021)
Atrial muscle cells treated with angiotensin II Macrophages miR-130 miR-130 promotes M1-type polarization of macrophages. Huang et al. (2022)
Oxidative stress-induced CMs Macrophages miR-106b-5p miR-106b-5p promotes M1-type polarization of macrophages. Li et al. (2023)
CMs induced by oxidative stress Hypoxic H9c2 miR-423-3p miR-423-3p promotes M1-type polarization of macrophages. Luo et al. (2019)
cCFU-FBs overexpressed by GATA4 gene H9c2 miR-221 miR-221 inhibits the expression of PTEN and activates the PTEN/PI3K/AKT signaling pathway, thereby alleviating the apoptosis of CMs. Hao et al. (2020)
I/R injury-induced FBs CMs miR-133a miR-133a targets ELAVL1 to inhibit the pyrodeath of CMs, thereby protecting CMs. Liu et al. (2022)
Fibroblasts subjected to mechanical stretch for 48 h CMs miR-143 miR-143 promotes apoptosis of CMs. Zhang (2018)
FBs CMs miR-21-3p miR-21-3p inhibits CMs targets SORBS2 and PDLIM5 and induce CMs hypertrophy. Bang et al. (2014)
FBs treated with TGF-β1 CMs miR-200a-3p miR-200a-3p inhibits the expression of VEGFA, HIF-1α, CD31, and angiopoietin 1 gene, inhibits proliferation, migration, and tubular formation, and promotes apoptosis. Ranjan et al. (2021)
Atrial MFBs induced by angiotensin II CMs miR-21-3p miR-21-3p down-regulates the expression of L-type calcium channel Cav1.2, a marker of ionic remodeling associated with atrial fibrillation in CMs, which may be a key substance in increasing the susceptibility to atrial fibrillation in the process of atrial fibrosis. Li et al. (2020)
Sca-1+ CPCs after MI CPCs induced by H2O2 miR-133a miR-133a promotes CPCs survival under oxidative stress by decreasing Caspase-3 activity and targeting the expression of pro-apoptotic genes Bim and Bmf. Izarra et al. (2014)
CPCs induced by oxidative stress H9c2 miR-21 miR-21 down-regulates PDCD4 and inhibits oxidative stress-induced apoptosis of H9c2 cells. Xiao et al. (2016)
CPCs CMs and ECs miR-210 and miR-132 miR-210 inhibited CMs apoptosis by down-regulating its target ephrin A3 and PTP1b; miR-132 enhanced tubular formation in ECs by down-regulating its target RasGAP-p120. Barile et al. (2014)
Sca-1+ CPCs HL-1 cells pre-miR-323-5p, pre-miR-181a, and pre-miR-132 Enhance cell tolerance to H/R damage. Cervio et al. (2014)
Endogenous GATA4 positive CPCs H9c2 miR-222 miR-222 protects H9c2 cells from apoptosis by mediating the PTEN-PI3K/AKT signalling pathway and improves their survival rate. Yu et al. (2015)
CPCs H9c2 treated with H2O2 for 4 h miR-451 miR-451 protects H9c2 cells from oxidative stress by inhibiting the activation of Caspase-3/Caspase-7. Chen et al. (2013)
CPCs iPSCs-derived CMs or CMs from newborn rats miR-528-3p and miR-7641 miR-528-3p and miR-7641 induced the proliferation of stationary CMs. Sharma et al. (2018)
CPCs treated with doxorubicin CMs induced by doxorubicin or trastuzumab miR-146a-5p miR-146a-5p attenuates oxidative stress damage induced by adriamycin/trastuzumab by inhibiting the expression of Traf6 and Mpo. Milano et al. (2020)
CPCs CMs and ECs miR-210, miR-146a and miR-132 miR-210 and miR-146a inhibited apoptosis of CMs by down-regulating ephrinA3/PTP1b signaling pathway and Nox4 target protein. miR-132 plays a pro-angiogenic role by down-regulating the target protein RasGAP-p120. Barile et al. (2015)
Bioengineered CPCs transfected by pro-angiogenic miR-322 ECs miR-322 miR-322 promotes angiogenesis. Youn et al. (2019)
Hypoxic induced CMECs H/R-induced H9c2 miR-27b-3p miR-27b-3p down-regulates the expression of GSDMD, NLRP3 and Caspase-1 in H9c2 cells by regulating Foxo1/GSDMD axis, thereby inhibiting pyroptosis. At the same time, the serum creatine kinase isozyme, lactate dehydrogenase, interleukin-1β, and interleukin-18 levels were significantly reduced. Zhang (2023)
CDCs H2O2-induced CMs miR-146a, miR-22, miR-24, miR-210, etc. miR-146a, miR-22, miR-24, miR-210, etc. inhibited CMs apoptosis and promoted cell proliferation. Ibrahim et al. (2013)
Hypoxic CDCs HUVECs miR-126, miR-130a, miR-210, and other pro-angiogenic miRNAs miR-126, miR-130a, miR-210, and other pro-angiogenic miRNAs promote tubular formation of HUVECs. Namazi et al. (2018)
CDCs Macrophages after ischemic preconditioning miR-181b miR-181b is an important candidate mediator for CDCs-induced macrophage polarization and plays a cardioprotective role by reducing PKCδ transcription levels. de Couto et al. (2017)
CMs after MI Tumor cells miR-22-3p miR-22-3p directly targets the ACSL4 gene of tumor cells, thereby inhibiting cell iron death induced by the eradicator of Ras and ST and accelerating tumor progression. Yuan et al. (2023)
CMs after MI Bone marrow progenitor cells miR-1, miR-208, and miR-499 miR-1, miR-208, and miR-499 inhibited CXCR4 expression and increased the number of CPCs. Cheng et al. (2019)

α-SMA, α smooth muscle actin; ACSL4, acyl-CoA synthetase long chain family member 4; AMI, acute myocardial infarction; cCFU-FBs, cardiac colony-forming unit fibroblasts; CMECs, cardiac microvascular endothelial cells; CMs, cardiomyocytes; CPCs, cardiac progenitor cells; CXCR4, C-X-C motif chemokine receptor 4; DYRK2, dual specificity tyrosine phosphorylation regulated kinase 2; ECs, endothelial cells; ELAVL1, ELAV-like RNA binding protein 1; ERK, extracellular regulated kinase; FBs, fibroblasts; GPX4: glutathione peroxidase 4; H/R, hypoxia/reoxygenation; HIF-1α, hypoxic inducible factor-1 α; UVECs, human umbilical vein endothelial cells; I/R; ischemia-reperfusion; iPSCs, induced pluripotent stem cells; JNK, c-Jun N-terminal kinase; MFBs, myofibroblasts; MI, myocardial infarction; miRNA, microRNA; PDCD4: programmed cell death 4; PTEN, tensin homolog deleted on chromosome ten; TGF-β1, transforming growth factor-β1; VEGFA, vascular endothelial growth factor A.