Extracorporeal Cardiac Shock Wave-Induced Exosome Derived From Endothelial Colony-Forming Cells Carrying miR-140-3p Alleviate Cardiomyocyte Hypoxia/Reoxygenation Injury via the PTEN/PI3K/AKT Pathway

Dan Yang, Mingqiang Wang, Zhao Hu, Yiming Ma, Yunke Shi, Xingyu Cao, Tao Guo, Hongbo Cai, Hongyan Cai, Dan Yang, Mingqiang Wang, Zhao Hu, Yiming Ma, Yunke Shi, Xingyu Cao, Tao Guo, Hongbo Cai, Hongyan Cai

Abstract

Background: Stem cell-derived exosomes have great potential in the treatment of myocardial ischemia-reperfusion injury (IRI). Extracorporeal cardiac shock waves (ECSW) as effective therapy, in part, could activate the function of exosomes. In this study, we explored the effect of ECSW-induced exosome derived from endothelial colony-forming cells on cardiomyocyte hypoxia/reoxygenation (H/R) injury and its underlying mechanisms. Methods: The exosomes were extracted and purified from the supernatant of endothelial colony-forming cells (ECFCs-exo). ECFCs-exo treated with shock wave (SW-exo) or without shock wave (CON-exo) were performed with high-throughput sequencing of the miRNA. H9c2 cells were incubated with SW-exo or CON-exo after H/R injury. The cell viability, cell apoptosis, oxidative stress level, and inflammatory factor were assessed. qRT-PCR was used to detect the expression levels of miRNA and mRNA in cells and exosomes. The PTEN/PI3K/AKT pathway-related proteins were detected by Western blotting, respectively. Results: Exosomes secreted by ECFCs could be taken up by H9c2 cells. Administration of SW-exo to H9c2 cells after H/R injury could significantly improve cell viability, inhibit cell apoptosis, and downregulate oxidative stress level (p < 0.01), with an increase in Bcl-2 protein and a decrease in Bax, cleaved caspase-3, and NF-κB protein (p < 0.05). Notably, miR-140-3p was found to be highly enriched both in ECFCs and ECFCs-exo treated with ECSW (p < 0.05) and served as a critical mediator. SW-exo increased miR-140-3p expression but decreased PTEN expression in H9c2 cells with enhanced phosphorylation of the PI3K/AKT signaling pathway. These cardioprotective effects of SW-exo on H/R injury were blunted by the miR-140-3p inhibitor. Dual-luciferase assay verified that miR-140-3p could directly target the 3'UTR of PTEN mRNA and exert a negative regulatory effect. Conclusion: This study has shown the potential of ECSW as an effective stimulation for the exosomes derived from ECFCs in vitro. SW-exo exerted a stronger therapeutic effect on H/R injury in H9c2 cells possibly via delivering exosomal miR-140-3p, which might be a novel promising strategy for the myocardial IRI.

Keywords: cardiomyocyte hypoxia/reoxygenation injury; endothelial colony-forming cells; exosomes; extracorporeal cardiac shock waves; miR-140-3p.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Yang, Wang, Hu, Ma, Shi, Cao, Guo, Cai and Cai.

Figures

FIGURE 1
FIGURE 1
Characterization of rat bone-derived endothelial colony-forming cells (ECFCs). (A) On day 3, day 7, day14, and day 21 of cellular morphology under an inverted microscope, scale bar = 100 μm. (B) Double staining of ECFCs positive for Dil-AcLDL and FITC-UEA-1 under fluorescent microscope, scale bar = 20 μm. (C) Cell surface markers (CD31, CD34, CD133, VEGFR-2, CD14, and CD45) of ECFCs were identified by flow cytometry. (D) Tube formation assay of ECFCs was evaluated under an inverted microscope, left: scale bar = 100 μm; right: scale bar = 50 μm.
FIGURE 2
FIGURE 2
Characterization of exosomes derived from ECFCs. (A-B). exosome morphology was evaluated via transmission electron microscopy, scale bar = 100–200 nm. (C-D) The size distribution of exosomes was analyzed by nanoparticle tracking analysis. The diameter of exosomes ranges mainly from 30 to 150 nm. (E) Western blot analysis of protein levels of CD9, CD63, CD81, and calnexin in cell lysis and ECFCs-exo. (F) H9c2 cells were incubated with PKH26 (positive control), PKH26-labeled exosomes, and unlabeled exosomes, nuclei were counterstained with DAPI, and the red fluorescence of PKH-26 in cells was traced by fluorescence microscope, scale bar = 20 μm.
FIGURE 3
FIGURE 3
Extracorporeal cardiac shock wave (ECSW)-induced ECFCs-exo protected cardiomyocytes against hypoxia/reoxygenation injury. (A) The cell viability of H9c2 cells after hypoxia/reoxygenation (H/R) injury treated with CON-exo and SW-exo at different concentrations from 0 to 40 µg/ml. *p < 0.05, **p < 0.01, within group; ##p < 0.01, between groups. (B–E) Quantitative analysis of the cell viability (B) by cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) activity (C) by reagent kit, cell apoptosis rate (D) by flow cytometry, and the production of reactive oxygen species (ROS) (E) by dichlorodihydrofluorescein diacetate (DCFH-DA) staining were shown for each group, including NC, H/R, and H9c2 cells after H/R injury treated with PBS, CON-exo, and SW-exo. Data are presented as mean ± SD, n = 3. *p < 0.05, **p < 0.01, E: scale bar = 50 μm.
FIGURE 4
FIGURE 4
ECSW-induced ECFCs-exo promoted the expression of Bcl-2 and inhibited the expressions of Bax, cleaved caspase-3, and NF-κB p65 in H9c2 cells. (A) Western blotting was used to detect the expression of Bcl-2, Bax, cleaved caspase-3, and NF-κB p65 in cardiomyocytes, normalized to the GAPDH protein. (B–E) Protein bands were analyzed using ImageJ software. Data are presented as mean ± SD, n = 3. *p < 0.05, **p < 0.01.
FIGURE 5
FIGURE 5
Characterization of miRNA sequences in SW-exo and CON-exo, and functional enrichment analysis. (A) Relative amounts of expression for 18 miRNAs enriched in SW-exo and CON-exo are displayed in a heat-map (p < 0.05, n = 4). (B) Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of differential target genes was displayed in a scatter plot. (C) Venn diagrams of detected miRNAs (SW-exo vs. CON-exo) shows a large overlap between the two groups. (D) Mapping of miR-140-3p and target gene network in the PI3K/AKT signaling pathway was drawn by Cytoscape software. (E) The relative expression of miR-140-3p in ECFCs and ECFCs-exo were detected by qRT-PCR normalized to U6 (n = 3). *p < 0.05, **p < 0.01.
FIGURE 6
FIGURE 6
SW-exo mainly delivered pivotal miR-140-3p to protect cardiomyocytes against hypoxia/reoxygenation injury. (A–D) Quantitative analysis of the cell viability (A) by CCK-8 assay, LDH activity (B) by reagent kit, cell apoptosis rate (C) by flow cytometry, and the production of ROS (D) by DCFH-DA staining are shown for each group, including H9c2 cells after H/R injury treated with miR-140-3p mimic, mimic NC, miR-140-3p inhibitor, inhibitor NC, and SW-exo. Data are presented as mean ± SD, n = 3. *p < 0.05, **p < 0.01, E: scale bar = 50 μm.
FIGURE 7
FIGURE 7
SW-exo delivered pivotal miR-140-3p to H9c2 cells for promoting the expression of Bcl-2 and inhibiting the expressions of Bax, cleaved caspase-3, and NF-κB p65. (A) Western blotting was used to detect the expression of Bcl-2, Bax, cleaved caspase-3, and NF-κB p65 in cardiomyocytes, normalized to the GAPDH protein. (B–E) Protein bands were analyzed using ImageJ software. Data are presented as mean ± SD, n = 3. *p < 0.05, **p < 0.01.
FIGURE 8
FIGURE 8
SW-exo containing miR-140-3p inhibited the expression of PTEN. (A) Profile of reporter vectors expressing luciferase fused with the 3′UTR of the PTEN wild type (WT) or mutant (MUT). (B) Potential binding sites (red) for miR-140-3p on PTEN 3′UTR are predicted, and mutated sequences are presented. (C) The relative luciferase activity was measured by dual-luciferase reporter gene assay (n = 3). (D) The relative expression of miR-140-3p and PTEN mRNA in H9c2 cells after transfected with miR-140-3p mimic or mimic NC, miR-140-3p inhibitor, or inhibitor NC were detected by qRT-PCR normalized to U6 and GAPDH (n = 3). *p < 0.05, **p < 0.01.
FIGURE 9
FIGURE 9
SW-exo exerted regulatory effect on the PTEN/PI3K/AKT signaling pathway via miR-140-3p in H9c2 cells. (A–D) Western blot was used to detect the expression of PTEN, p-PI3K, PI3K, p-AKT, and AKT, normalized to the GAPDH protein. (E, F) The relative expression of miR-140-3p and PTEN mRNA in H9c2 cells were detected by qRT-PCR, normalized to U6 and GAPDH. Data are presented as mean ± SD, n = 3. *p < 0.05, **p < 0.01.
FIGURE 10
FIGURE 10
miR-140-3p inhibitor reversed the effect of SW-exo by blunting the PTEN/PI3K/AKT signaling pathway in H9c2 cells. (A–D) Western blot was used to detect the expression of PTEN, p-PI3K, PI3K, p-AKT, and AKT, normalized to the GAPDH protein. (E, F) The relative expression of miR-140-3p and PTEN mRNA in cardiomyocytes were detected by qRT-PCR, normalized to U6 and GAPDH. Data are presented as mean ± SD, n = 3. *p < 0.05, **p < 0.01.

References

    1. Arslan F., Lai R. C., Smeets M. B., Akeroyd L., Choo A., Aguor E. N. E., et al. (2013). Mesenchymal Stem Cell-Derived Exosomes Increase ATP Levels, Decrease Oxidative Stress and Activate PI3K/Akt Pathway to Enhance Myocardial Viability and Prevent Adverse Remodeling after Myocardial Ischemia/reperfusion Injury. Stem Cel Res. 10, 301–312. 10.1016/j.scr.2013.01.002
    1. Bai S., Yin Q., Dong T., Dai F., Qin Y., Ye L., et al. (2020). Endothelial Progenitor Cell-Derived Exosomes Ameliorate Endothelial Dysfunction in a Mouse Model of Diabetes. Biomed. Pharmacother. 131, 110756. 10.1016/j.biopha.2020.110756
    1. Bartolucci J., Verdugo F. J., González P. L., Larrea R. E., Abarzua E., Goset C., et al. (2017). Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients with Heart Failure. Circ. Res. 121, 1192–1204. 10.1161/circresaha.117.310712
    1. Betel D., Koppal A., Agius P., Sander C., Leslie C. (2010). Comprehensive Modeling of microRNA Targets Predicts Functional Non-conserved and Non-canonical Sites. Genome Biol. 11, R90. 10.1186/gb-2010-11-8-r90
    1. Bugger H., Pfeil K. (2020). Mitochondrial ROS in Myocardial Ischemia Reperfusion and Remodeling. Biochim. Biophys. Acta (Bba) - Mol. Basis Dis. 1866, 165768. 10.1016/j.bbadis.2020.165768
    1. Bulluck H., Yellon D. M., Hausenloy D. J. (2016). Reducing Myocardial Infarct Size: Challenges and Future Opportunities. Heart 102, 341–348. 10.1136/heartjnl-2015-307855
    1. Burger D., Viñas J. L., Akbari S., Dehak H., Knoll W., Gutsol A., et al. (2015). Human Endothelial Colony-Forming Cells Protect against Acute Kidney Injury. Am. J. Pathol. 185, 2309–2323. 10.1016/j.ajpath.2015.04.010
    1. Cai H.-Y., Li L., Guo T., Wang Y., Ma T.-K., Xiao J.-M., et al. (2015). Cardiac Shockwave Therapy Improves Myocardial Function in Patients with Refractory Coronary Artery Disease by Promoting VEGF and IL-8 Secretion to Mediate the Proliferation of Endothelial Progenitor Cells. Exp. Ther. Med. 10, 2410–2416. 10.3892/etm.2015.2820
    1. Ceccon C. L., Duque A. S., Gowdak L. H., Mathias W., Jr., Chiang H. P., Sbano J. C. N., et al. (2019). Shock-Wave Therapy Improves Myocardial Blood Flow Reserve in Patients with Refractory Angina: Evaluation by Real-Time Myocardial Perfusion Echocardiography. J. Am. Soc. Echocardiography 32, 1075–1085. 10.1016/j.echo.2019.04.420
    1. Cselenyák A., Pankotai E., Horváth E. M., Kiss L., Lacza Z. (2010). Mesenchymal Stem Cells rescue Cardiomyoblasts from Cell Death in an In Vitro Ischemia Model via Direct Cell-To-Cell Connections. BMC Cel Biol 11, 29. 10.1186/1471-2121-11-29
    1. Davidson S. M., Ferdinandy P., Andreadou I., Bøtker H. E., Heusch G., Ibáñez B., et al. (2019). Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury. J. Am. Coll. Cardiol. 73, 89–99. 10.1016/j.jacc.2018.09.086
    1. Der Sarkissian S., Lévesque T., Noiseux N. (2017). Optimizing Stem Cells for Cardiac Repair: Current Status and New Frontiers in Regenerative Cardiology. Wjsc 9, 9–25. 10.4252/wjsc.v9.i1.9
    1. Eltzschig H. K., Eckle T. (2011). Ischemia and Reperfusion-From Mechanism to Translation. Nat. Med. 17, 1391–1401. 10.1038/nm.2507
    1. Feng Q., Li X., Qin X., Yu C., Jin Y., Qian X. (2020). PTEN Inhibitor Improves Vascular Remodeling and Cardiac Function after Myocardial Infarction through PI3k/Akt/VEGF Signaling Pathway. Mol. Med. 26, 111. 10.1186/s10020-020-00241-8
    1. Feng Y., Huang W., Wani M., Yu X., Ashraf M. (2014). Ischemic Preconditioning Potentiates the Protective Effect of Stem Cells through Secretion of Exosomes by Targeting Mecp2 via miR-22. PLoS One 9, e88685. 10.1371/journal.pone.0088685
    1. Ghosh A., Dasgupta D., Ghosh A., Roychoudhury S., Kumar D., Gorain M., et al. (2017). MiRNA199a-3p Suppresses Tumor Growth, Migration, Invasion and Angiogenesis in Hepatocellular Carcinoma by Targeting VEGFA, VEGFR1, VEGFR2, HGF and MMP2. Cell Death Dis 8, e2706. 10.1038/cddis.2017.123
    1. Gollmann‐Tepeköylü C., Lobenwein D., Theurl M., Primessnig U., Lener D., Kirchmair E., et al. (2018). Shock Wave Therapy Improves Cardiac Function in a Model of Chronic Ischemic Heart Failure: Evidence for a Mechanism Involving VEGF Signaling and the Extracellular Matrix. J. Am. Heart Assoc. 7, e010025. 10.1161/jaha.118.010025
    1. Gollmann-Tepeköylü C., Pölzl L., Graber M., Hirsch J., Nägele F., Lobenwein D., et al. (2020). miR-19a-3p Containing Exosomes Improve Function of Ischaemic Myocardium upon Shock Wave Therapy. Cardiovasc. Res. 116, 1226–1236. 10.1093/cvr/cvz209
    1. Gong M., Li Z., Zhang X., Liu B., Luo J., Qin X., et al. (2021). PTEN Mediates Serum Deprivation-Induced Cytotoxicity in H9c2 Cells via the PI3K/AKT Signaling Pathway. Toxicol. Vitro 73, 105131. 10.1016/j.tiv.2021.105131
    1. Goradel N. H., Hour F. G., Negahdari B., Malekshahi Z. V., Hashemzehi M., Masoudifar A., et al. (2018). Stem Cell Therapy: A New Therapeutic Option for Cardiovascular Diseases. J. Cel. Biochem. 119, 95–104. 10.1002/jcb.26169
    1. Hao L. Y., Lu Y., Ma Y. C., Wei R. P., Jia Y. P. (2020). MiR-140 Protects against Myocardial Ischemia-Reperfusion Injury by Regulating NF-Κb Pathway. Eur. Rev. Med. Pharmacol. Sci. 24, 11266–11272. 10.26355/eurrev_202011_23616
    1. Hausenloy D. J., Botker H. E., Engstrom T., Erlinge D., Heusch G., Ibanez B., et al. (2017). Targeting Reperfusion Injury in Patients with ST-Segment Elevation Myocardial Infarction: Trials and Tribulations. Eur. Heart J. 38, ehw145–941. 10.1093/eurheartj/ehw145
    1. Hausenloy D. J., Yellon D. M. (2013). Myocardial Ischemia-Reperfusion Injury: a Neglected Therapeutic Target. J. Clin. Invest. 123, 92–100. 10.1172/jci62874
    1. Hu H., Wang B., Jiang C., Li R., Zhao J. (2019). Endothelial Progenitor Cell-Derived Exosomes Facilitate Vascular Endothelial Cell Repair through Shuttling miR-21-5p to Modulate Thrombospondin-1 Expression. Clin. Sci. (Lond). 133, 1629–1644. 10.1042/cs20190188
    1. Hu Y., Rao S.-S., Wang Z.-X., Cao J., Tan Y.-J., Luo J., et al. (2018a). Exosomes from Human Umbilical Cord Blood Accelerate Cutaneous Wound Healing through miR-21-3p-Mediated Promotion of Angiogenesis and Fibroblast Function. Theranostics 8, 169–184. 10.7150/thno.21234
    1. Hu Z., Cai H.-Y., Luo Y.-Y., Xiao J.-M., Li L., Guo T. (2018b). Effect of Varying Hypoxia Reoxygenation Times on Autophagy of Cardiomyocytes. Acta Cir. Bras. 33, 223–230. 10.1590/s0102-865020180030000004
    1. Huang H., Wang Y., Li Q., Fei X., Ma H., Hu R. (2019). miR-140-3p Functions as a Tumor Suppressor in Squamous Cell Lung Cancer by Regulating BRD9. Cancer Lett. 446, 81–89. 10.1016/j.canlet.2019.01.007
    1. Huang Y., Chen L., Feng Z., Chen W., Yan S., Yang R., et al. (2021). EPC-derived Exosomal miR-1246 and miR-1290 Regulate Phenotypic Changes of Fibroblasts to Endothelial Cells to Exert Protective Effects on Myocardial Infarction by Targeting ELF5 and SP1. Front. Cel Dev. Biol. 9, 647763. 10.3389/fcell.2021.647763
    1. Jude J. A., Dileepan M., Subramanian S., Solway J., Panettieri R. A., Jr., Walseth T. F., et al. (2012). miR-140-3p Regulation of TNF-α-Induced CD38 Expression in Human Airway Smooth Muscle Cells. Am. J. Physiology-Lung Cell Mol. Physiol. 303, L460–L468. 10.1152/ajplung.00041.2012
    1. Kagaya Y., Ito K., Takahashi J., Matsumoto Y., Shiroto T., Tsuburaya R., et al. (2018). Low-energy Cardiac Shockwave Therapy to Suppress Left Ventricular Remodeling in Patients with Acute Myocardial Infarction. Coron. Artery Dis. 29, 294–300. 10.1097/MCA.0000000000000577
    1. Karakas M., Schulte C., Appelbaum S., Ojeda F., Lackner K. J., Münzel T., et al. (2017). Circulating microRNAs Strongly Predict Cardiovascular Death in Patients with Coronary Artery Disease-Results from the Large AtheroGene Study. Eur. Heart J. 38, ehw250–523. 10.1093/eurheartj/ehw250
    1. Ke X., Yang R., Wu F., Wang X., Liang J., Hu X., et al. (2021). Exosomal miR-218-5p/miR-363-3p from Endothelial Progenitor Cells Ameliorate Myocardial Infarction by Targeting the P53/JMY Signaling Pathway. Oxidative Med. Cell Longevity 2021, 1–23. 10.1155/2021/5529430
    1. Kikuchi Y., Ito K., Shindo T., Hao K., Shiroto T., Matsumoto Y., et al. (2018). A Multicenter Trial of Extracorporeal Cardiac Shock Wave Therapy for Refractory Angina Pectoris: Report of the Highly Advanced Medical Treatment in Japan. Heart Vessels 34, 104–113. 10.1007/s00380-018-1215-4
    1. Li X.-D., Yang Y.-J., Wang L.-Y., Qiao S.-B., Lu X.-F., Wu Y.-J., et al. (2017). Elevated Plasma miRNA-122, -140-3p, -720, -2861, and -3149 during Early Period of Acute Coronary Syndrome Are Derived from Peripheral Blood Mononuclear Cells. PLoS One 12, e0184256. 10.1371/journal.pone.0184256
    1. Liang S., Ren K., Li B., Li F., Liang Z., Hu J., et al. (2020). LncRNA SNHG1 Alleviates Hypoxia-Reoxygenation-Induced Vascular Endothelial Cell Injury as a Competing Endogenous RNA through the HIF-1α/VEGF Signal Pathway. Mol. Cel Biochem 465, 1–11. 10.1007/s11010-019-03662-0
    1. Lin J., Ma X. (2019). Detection of Serum MiR-140-3p and MiR-142-5p Levels and Relationship Among Them and Cardiovascular Outcomes and Mortality in Patients with Coronary Heart Disease. Chin. J. Evid. Based Cardiovasc. Med. 11, 312–315. 10.3969/j.issn.1674-4055.2019.03.11
    1. Ling H., Guo Z., Shi Y., Zhang L., Song C. (2020). Serum Exosomal MicroRNA-21, MicroRNA-126, and PTEN Are Novel Biomarkers for Diagnosis of Acute Coronary Syndrome. Front. Physiol. 11, 654. 10.3389/fphys.2020.00654
    1. Ma C., Wang J., Liu H., Chen Y., Ma X., Chen S., et al. (2018). Moderate Exercise Enhances Endothelial Progenitor Cell Exosomes Release and Function. Med. Sci. Sports Exerc. 50, 2024–2032. 10.1249/MSS.0000000000001672
    1. Ma Y., Hu Z., Yang D., Li L., Wang L., Xiao J., et al. (2020). Extracorporeal Cardiac Shock Waves Therapy Promotes Function of Endothelial Progenitor Cells through PI3K/AKT and MEK/ERK Signaling Pathways. Am. J. Transl Res. 12, 3895–3905.
    1. Medina R. J., Barber C. L., Sabatier F., Dignat-George F., Melero-Martin J. M., Khosrotehrani K., et al. (2017). Endothelial Progenitors: A Consensus Statement on Nomenclature. STEM CELLS Translational Med. 6, 1316–1320. 10.1002/sctm.16-0360
    1. Menasché P., Vanneaux V., Hagège A., Bel A., Cholley B., Cacciapuoti I., et al. (2015). Human Embryonic Stem Cell-Derived Cardiac Progenitors for Severe Heart Failure Treatment: First Clinical Case Report: Figure 1. Eur. Heart J. 36, 2011–2017. 10.1093/eurheartj/ehv189
    1. Musunuru K., Sheikh F., Gupta R. M., Houser S. R., Maher K. O., Milan D. J., et al. (2018). Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling and Precision Medicine: A Scientific Statement from the American Heart Association. Circ. Genomic Precision Med. 11, e000043. 10.1161/hcg.0000000000000043
    1. Nam J.-W., Rissland O. S., Koppstein D., Abreu-Goodger C., Jan C. H., Agarwal V., et al. (2014). Global Analyses of the Effect of Different Cellular Contexts on microRNA Targeting. Mol. Cel 53, 1031–1043. 10.1016/j.molcel.2014.02.013
    1. Neri M., Riezzo I., Pascale N., Pomara C., Turillazzi E. (2017). Ischemia/Reperfusion Injury Following Acute Myocardial Infarction: A Critical Issue for Clinicians and Forensic Pathologists. Mediators Inflamm. 2017, 1–14. 10.1155/2017/7018393
    1. Nishida T., Shimokawa H., Oi K., Tatewaki H., Uwatoku T., Abe K., et al. (2004). Extracorporeal Cardiac Shock Wave Therapy Markedly Ameliorates Ischemia-Induced Myocardial Dysfunction in Pigs In Vivo . Circulation 110, 3055–3061. 10.1161/01.cir.0000148849.51177.97
    1. Ntoumou E., Tzetis M., Braoudaki M., Lambrou G., Poulou M., Malizos K., et al. (2017). Serum microRNA Array Analysis Identifies miR-140-3p, miR-33b-3p and miR-671-3p as Potential Osteoarthritis Biomarkers Involved in Metabolic Processes. Clin. Epigenet 9, 127. 10.1186/s13148-017-0428-1
    1. Parajuli N., Yuan Y., Zheng X., Bedja D., Cai Z. P. (2012). Phosphatase PTEN Is Critically Involved in post-myocardial Infarction Remodeling through the Akt/interleukin-10 Signaling Pathway. Basic Res. Cardiol. 107, 248. 10.1007/s00395-012-0248-6
    1. Reed G. W., Rossi J. E., Cannon C. P. (2017). Acute Myocardial Infarction. The Lancet 389, 197–210. 10.1016/s0140-6736(16)30677-8
    1. Ribeiro-Rodrigues T. M., Laundos T. L., Pereira-CarvalhoTiago R., Batista-AlmeidaBatista-Almeida D., Pereira R., Silva V. A. P., et al. (2017). Exosomes Secreted by Cardiomyocytes Subjected to Ischaemia Promote Cardiac Angiogenesis. Cardiovasc. Res. 113, 1338–1350. 10.1093/cvr/cvx118
    1. Sahoo S., Klychko E., Thorne T., Misener S., Schultz K. M., Millay M., et al. (2011). Exosomes from Human CD34 + Stem Cells Mediate Their Proangiogenic Paracrine Activity. Circ. Res. 109, 724–728. 10.1161/circresaha.111.253286
    1. Schiffelers R., Kooijmans S., Vader S. M., van Dommelen W. W., Van Solinge R. M. (2012). Exosome Mimetics: a Novel Class of Drug Delivery Systems. Int. J. Nano. 7, 1525–1541. 10.2147/ijn.s29661
    1. Sousa B., Melo T., Campos A., Moreira A. S. P., Maciel E., Domingues P., et al. (2016). Alteration in Phospholipidome Profile of Myoblast H9c2 Cell Line in a Model of Myocardium Starvation and Ischemia. J. Cel. Physiol. 231, 2266–2274. 10.1002/jcp.25344
    1. Stone G. W., Selker H. P., Thiele H., Patel M. R., Udelson J. E., Ohman E. M., et al. (2016). Relationship between Infarct Size and Outcomes Following Primary PCI. J. Am. Coll. Cardiol. 67, 1674–1683. 10.1016/j.jacc.2016.01.069
    1. Vicencio J. M., Yellon D. M., Sivaraman V., Das D., Boi-Doku C., Arjun S., et al. (2015). Plasma Exosomes Protect the Myocardium from Ischemia-Reperfusion Injury. J. Am. Coll. Cardiol. 65, 1525–1536. 10.1016/j.jacc.2015.02.026
    1. Wang J., Chen S., Zhang W., Chen Y., Bihl J. C. (2020a). Exosomes from miRNA‐126‐modified Endothelial Progenitor Cells Alleviate Brain Injury and Promote Functional Recovery after Stroke. CNS Neurosci. Ther. 26, 1255–1265. 10.1111/cns.13455
    1. Wang J., Liu H., Chen S., Zhang W., Chen Y., Yang Y. (2020b). Moderate Exercise Has Beneficial Effects on Mouse Ischemic Stroke by Enhancing the Functions of Circulating Endothelial Progenitor Cell-Derived Exosomes. Exp. Neurol. 330, 113325. 10.1016/j.expneurol.2020.113325
    1. Wang L., Tian X., Cao Y., Ma X., Shang L., Li H., et al. (2021). Cardiac Shock Wave Therapy Improves Ventricular Function by Relieving Fibrosis through PI3K/Akt Signaling Pathway: Evidence from a Rat Model of Post-infarction Heart Failure. Front. Cardiovasc. Med. 8, 693875. 10.3389/fcvm.2021.693875
    1. Wang W. W., Zhang H. M., Wang L., Bao T. H. (2017). Scutellarin Protects against Myocardial Ischemia-Reperfusion Injury by Upregulating miR-140 Expression. Nat. Prod. Res. Dev. 29, 299–303. 10.16333/j.1001-6880.2017.2.021
    1. Ward M. R., Stewart D. J., Kutryk M. J. B. (2007). Endothelial Progenitor Cell Therapy for the Treatment of Coronary Disease, Acute MI, and Pulmonary Arterial Hypertension: Current Perspectives. Cathet. Cardiovasc. Intervent. 70, 983–998. 10.1002/ccd.21302
    1. Wojakowski W., Landmesser U., Bachowski R., Jadczyk T., Tendera M. (2012). Mobilization of Stem and Progenitor Cells in Cardiovascular Diseases. Leukemia 26, 23–33. 10.1038/leu.2011.184
    1. Wu S.-M., Li T.-H., Yun H., Ai H.-W., Zhang K.-H. (2019). miR-140-3p Knockdown Suppresses Cell Proliferation and Fibrogenesis in Hepatic Stellate Cells via PTEN-Mediated AKT/mTOR Signaling. Yonsei Med. J. 60, 561–569. 10.3349/ymj.2019.60.6.561
    1. Xu J., Bai S., Cao Y., Liu L., Fang Y., Du J., et al. (2020). miRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice. Dmso Vol. 13, 1259–1270. 10.2147/dmso.s243549
    1. Yi M., Li Y., Wang D., Zhang Q., Yang L., Yang C. (2020). KCNQ1OT1 Exacerbates Ischemia-Reperfusion Injury through Targeted Inhibition of miR-140-3P. Inflammation 43, 1832–1845. 10.1007/s10753-020-01257-2
    1. Yu S., Li Z., Zhang W., Du Z., Liu K., Yang D., et al. (2018). Isolation and Characterization of Endothelial colony-forming Cells from Mononuclear Cells of Rat Bone Marrow. Exp. Cel Res. 370, 116–126. 10.1016/j.yexcr.2018.06.013
    1. Yue Y., Wang C., Benedict C., Huang G., Truongcao M., Roy R., et al. (2020). Interleukin-10 Deficiency Alters Endothelial Progenitor Cell-Derived Exosome Reparative Effect on Myocardial Repair via Integrin-Linked Kinase Enrichment. Circ. Res. 126, 315–329. 10.1161/CIRCRESAHA.119.315829
    1. Zeng C.-Y., Xu J., Liu X., Lu Y.-Q. (2021). Cardioprotective Roles of Endothelial Progenitor Cell-Derived Exosomes. Front. Cardiovasc. Med. 8, 717536. 10.3389/fcvm.2021.717536
    1. Zheng D., Huo M., Li B., Wang W., Piao H., Wang Y., et al. (2020). The Role of Exosomes and Exosomal MicroRNA in Cardiovascular Disease. Front. Cel Dev. Biol. 8, 616161. 10.3389/fcell.2020.616161
    1. Zhou Y., Li P., Goodwin A. J., Cook J. A., Halushka P. V., Chang E., et al. (2019). Exosomes from Endothelial Progenitor Cells Improve Outcomes of the Lipopolysaccharide-Induced Acute Lung Injury. Crit. Care 23, 44. 10.1186/s13054-019-2339-3

Source: PubMed

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