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M1-like macrophage-derived exosomes suppress angiogenesis and exacerbate cardiac dysfunction in a myocardial infarction microenvironment

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Abstract

The roles and the underlying mechanisms of M1-type macrophages in angiogenesis and postmyocardial infarction (MI) cardiac repair have remained unclear. In this study, we investigated the role of M1-like macrophage-derived exosomes in a MI microenvironment. We found that the proinflammatory M1-like-type macrophages released an extensive array of proinflammatory exosomes (M1-Exos) after MI. M1-Exos exerted an anti-angiogenic effect and accelerated MI injury. They also exhibited highly expressed proinflammatory miRNAs, such as miR-155. miR-155 was transferred to endothelial cells (ECs), leading to the inhibition of angiogenesis and cardiac dysfunction by downregulating its novel target genes, including Rac family small GTPase 1 (RAC1), p21 (RAC1)-activated kinase 2 (PAK2), Sirtuin 1 (Sirt1), and protein kinase AMP-activated catalytic subunit alpha 2 (AMPKα2). M1-Exos depressed Sirt1/AMPKα2–endothelial nitric oxide synthase and RAC1–PAK2 signaling pathways by simultaneously targeting the five molecule nodes (genes), reduced the angiogenic ability of ECs, aggravated myocardial injury, and restrained cardiac healing. The elucidation of this mechanism provides novel insights into the functional significance of M1 macrophages and their derived exosomes on angiogenesis and cardiac repair. This mechanism can be used as a novel potential therapeutic approach for the prevention and treatment of MI.

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References

  1. Aurora AB, Porrello ER, Tan W, Mahmoud AI, Hill JA, Bassel-Duby R, Sadek HA, Olson EN (2014) Macrophages are required for neonatal heart regeneration. J Clin Invest 124:1382–1392. https://doi.org/10.1172/JCI72181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ben-Mordechai T, Holbova R, Landa-Rouben N, Harel-Adar T, Feinberg MS, Abd Elrahman I, Blum G, Epstein FH, Silman Z, Cohen S, Leor J (2013) Macrophage subpopulations are essential for infarct repair with and without stem cell therapy. J Am Coll Cardiol 62:1890–1901. https://doi.org/10.1016/j.jacc.2013.07.057

    Article  PubMed  Google Scholar 

  3. Ben-Mordechai T, Palevski D, Glucksam-Galnoy Y, Elron-Gross I, Margalit R, Leor J (2015) Targeting macrophage subsets for infarct repair. J Cardiovasc Pharmacol Ther 20:36–51. https://doi.org/10.1177/1074248414534916

    Article  PubMed  Google Scholar 

  4. Botker HE, Hausenloy D, Andreadou I, Antonucci S, Boengler K, Davidson SM, Deshwal S, Devaux Y, Di Lisa F, Di Sante M, Efentakis P, Femmino S, Garcia-Dorado D, Giricz Z, Ibanez B, Iliodromitis E, Kaludercic N, Kleinbongard P, Neuhauser M, Ovize M, Pagliaro P, Rahbek-Schmidt M, Ruiz-Meana M, Schluter KD, Schulz R, Skyschally A, Wilder C, Yellon DM, Ferdinandy P, Heusch G (2018) Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection. Basic Res Cardiol 113:39. https://doi.org/10.1007/s00395-018-0696-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cheng Y, Rong J (2018) Macrophage polarization as a therapeutic target in myocardial infarction. Curr Drug Targets 19:651–662. https://doi.org/10.2174/1389450118666171031115025

    Article  CAS  PubMed  Google Scholar 

  6. Corliss BA, Azimi MS, Munson JM, Peirce SM, Murfee WL (2016) Macrophages: an inflammatory link between angiogenesis and lymphangiogenesis. Microcirculation 23:95–121. https://doi.org/10.1111/micc.12259

    Article  PubMed  PubMed Central  Google Scholar 

  7. Deveza L, Choi J, Yang F (2012) Therapeutic angiogenesis for treating cardiovascular diseases. Theranostics 2:801–814. https://doi.org/10.7150/thno.4419

    Article  PubMed  PubMed Central  Google Scholar 

  8. Eisenhardt SU, Weiss JB, Smolka C, Maxeiner J, Pankratz F, Bemtgen X, Kustermann M, Thiele JR, Schmidt Y, Bjoern Stark G, Moser M, Bode C, Grundmann S (2015) MicroRNA-155 aggravates ischemia-reperfusion injury by modulation of inflammatory cell recruitment and the respiratory oxidative burst. Basic Res Cardiol 110:32. https://doi.org/10.1007/s00395-015-0490-9

    Article  CAS  PubMed  Google Scholar 

  9. Frangogiannis NG (2015) Inflammation in cardiac injury, repair and regeneration. Curr Opin Cardiol 30:240–245. https://doi.org/10.1097/HCO.0000000000000158

    Article  PubMed  PubMed Central  Google Scholar 

  10. Guo J, Liu HB, Sun C, Yan XQ, Hu J, Yu J, Yuan Y, Du ZM (2019) MicroRNA-155 promotes myocardial infarction-induced apoptosis by targeting RNA-binding protein QKI. Oxid Med Cell Longev 2019:4579806. https://doi.org/10.1155/2019/4579806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Harel-Adar T, Ben Mordechai T, Amsalem Y, Feinberg MS, Leor J, Cohen S (2011) Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair. Proc Natl Acad Sci USA 108:1827–1832. https://doi.org/10.1073/pnas.1015623108

    Article  PubMed  Google Scholar 

  12. Hausenloy DJ, Chilian W, Crea F, Davidson SM, Ferdinandy P, Garcia-Dorado D, van Royen N, Schulz R, Heusch G (2019) The coronary circulation in acute myocardial ischaemia/reperfusion injury: a target for cardioprotection. Cardiovasc Res 115:1143–1155. https://doi.org/10.1093/cvr/cvy286

    Article  CAS  PubMed  Google Scholar 

  13. He W, Huang H, Xie Q, Wang Z, Fan Y, Kong B, Huang D, Xiao Y (2016) MiR-155 knockout in fibroblasts improves cardiac remodeling by targeting tumor protein p53-inducible nuclear protein 1. J Cardiovasc Pharmacol Ther 21:423–435. https://doi.org/10.1177/1074248415616188

    Article  CAS  PubMed  Google Scholar 

  14. Hesketh M, Sahin KB, West ZE, Murray RZ (2017) Macrophage phenotypes regulate scar formation and chronic wound healing. Int J Mol Sci. https://doi.org/10.3390/ijms18071545

    Article  PubMed  PubMed Central  Google Scholar 

  15. Heusch G (2016) The coronary circulation as a target of cardioprotection. Circ Res 118:1643–1658. https://doi.org/10.1161/CIRCRESAHA.116.308640

    Article  CAS  PubMed  Google Scholar 

  16. Heusch G (2019) Coronary microvascular obstruction: the new frontier in cardioprotection. Basic Res Cardiol 114:45. https://doi.org/10.1007/s00395-019-0756-8

    Article  CAS  PubMed  Google Scholar 

  17. Hu J, Huang CX, Rao PP, Cao GQ, Zhang Y, Zhou JP, Zhu LY, Liu MX, Zhang GG (2019) MicroRNA-155 inhibition attenuates endoplasmic reticulum stress-induced cardiomyocyte apoptosis following myocardial infarction via reducing macrophage inflammation. Eur J Pharmacol 857:172449. https://doi.org/10.1016/j.ejphar.2019.172449

    Article  CAS  PubMed  Google Scholar 

  18. Hu J, Huang CX, Rao PP, Zhou JP, Wang X, Tang L, Liu MX, Zhang GG (2019) Inhibition of microRNA-155 attenuates sympathetic neural remodeling following myocardial infarction via reducing M1 macrophage polarization and inflammatory responses in mice. Eur J Pharmacol 851:122–132. https://doi.org/10.1016/j.ejphar.2019.02.001

    Article  CAS  PubMed  Google Scholar 

  19. Hu M, Guo G, Huang Q, Cheng C, Xu R, Li A, Liu N, Liu S (2018) The harsh microenvironment in infarcted heart accelerates transplanted bone marrow mesenchymal stem cells injury: the role of injured cardiomyocytes-derived exosomes. Cell Death Dis 9:357. https://doi.org/10.1038/s41419-018-0392-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hu Y, Zhang H, Lu Y, Bai H, Xu Y, Zhu X, Zhou R, Ben J, Xu Y, Chen Q (2011) Class A scavenger receptor attenuates myocardial infarction-induced cardiomyocyte necrosis through suppressing M1 macrophage subset polarization. Basic Res Cardiol 106:1311–1328. https://doi.org/10.1007/s00395-011-0204-x

    Article  CAS  PubMed  Google Scholar 

  21. Ishikawa S, Noma T, Fu HY, Matsuzaki T, Ishizawa M, Ishikawa K, Murakami K, Nishimoto N, Nishiyama A, Minamino T (2017) Apoptosis inhibitor of macrophage depletion decreased M1 macrophage accumulation and the incidence of cardiac rupture after myocardial infarction in mice. PLoS ONE 12:e0187894. https://doi.org/10.1371/journal.pone.0187894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jablonski KA, Gaudet AD, Amici SA, Popovich PG, Guerau-de-Arellano M (2016) Control of the inflammatory macrophage transcriptional signature by miR-155. PLoS ONE 11:e0159724. https://doi.org/10.1371/journal.pone.0159724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q, Zimmerman LJ, Liebler DC, Ping J, Liu Q, Evans R, Fissell WH, Patton JG, Rome LH, Burnette DT, Coffey RJ (2019) Reassessment of exosome composition. Cell 177(428–445):e418. https://doi.org/10.1016/j.cell.2019.02.029

    Article  CAS  Google Scholar 

  24. Jetten N, Verbruggen S, Gijbels MJ, Post MJ, De Winther MP, Donners MM (2014) Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo. Angiogenesis 17:109–118. https://doi.org/10.1007/s10456-013-9381-6

    Article  CAS  PubMed  Google Scholar 

  25. Jung M, Dodsworth M, Thum T (2018) Inflammatory cells and their non-coding RNAs as targets for treating myocardial infarction. Basic Res Cardiol 114:4. https://doi.org/10.1007/s00395-018-0712-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Koh W, Mahan RD, Davis GE (2008) Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling. J Cell Sci 121:989–1001. https://doi.org/10.1242/jcs.020693

    Article  CAS  PubMed  Google Scholar 

  27. Kong W, He L, Richards EJ, Challa S, Xu CX, Permuth-Wey J, Lancaster JM, Coppola D, Sellers TA, Djeu JY, Cheng JQ (2014) Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer. Oncogene 33:679–689. https://doi.org/10.1038/onc.2012.636

    Article  CAS  PubMed  Google Scholar 

  28. Kroller-Schon S, Jansen T, Tran TLP, Kvandova M, Kalinovic S, Oelze M, Keaney JF Jr, Foretz M, Viollet B, Daiber A, Kossmann S, Lagrange J, Frenis K, Wenzel P, Munzel T, Schulz E (2019) Endothelial alpha1AMPK modulates angiotensin II-mediated vascular inflammation and dysfunction. Basic Res Cardiol 114:8. https://doi.org/10.1007/s00395-019-0717-2

    Article  CAS  PubMed  Google Scholar 

  29. Lambert JM, Lopez EF, Lindsey ML (2008) Macrophage roles following myocardial infarction. Int J Cardiol 130:147–158. https://doi.org/10.1016/j.ijcard.2008.04.059

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lan J, Sun L, Xu F, Liu L, Hu F, Song D, Hou Z, Wu W, Luo X, Wang J, Yuan X, Hu J, Wang G (2019) M2 macrophage-derived exosomes promote cell migration and invasion in colon cancer. Cancer Res 79:146–158. https://doi.org/10.1158/0008-5472.CAN-18-0014

    Article  CAS  PubMed  Google Scholar 

  31. Lawrence T, Natoli G (2011) Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 11:750–761. https://doi.org/10.1038/nri3088

    Article  CAS  PubMed  Google Scholar 

  32. Lee HD, Kim YH, Kim DS (2014) Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking. Eur J Immunol 44:1156–1169. https://doi.org/10.1002/eji.201343660

    Article  CAS  PubMed  Google Scholar 

  33. Leuschner F, Dutta P, Gorbatov R, Novobrantseva TI, Donahoe JS, Courties G, Lee KM, Kim JI, Markmann JF, Marinelli B, Panizzi P, Lee WW, Iwamoto Y, Milstein S, Epstein-Barash H, Cantley W, Wong J, Cortez-Retamozo V, Newton A, Love K, Libby P, Pittet MJ, Swirski FK, Koteliansky V, Langer R, Weissleder R, Anderson DG, Nahrendorf M (2011) Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat Biotechnol 29:1005–1010. https://doi.org/10.1038/nbt.1989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Li J, Li SH, Wu J, Weisel RD, Yao A, Stanford WL, Liu SM, Li RK (2018) Young bone marrow Sca-1 cells rejuvenate the aged heart by promoting epithelial-to-mesenchymal transition. Theranostics 8:1766–1781. https://doi.org/10.7150/thno.22788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lindsey ML, Bolli R, Canty JM Jr, Du XJ, Frangogiannis NG, Frantz S, Gourdie RG, Holmes JW, Jones SP, Kloner RA, Lefer DJ, Liao R, Murphy E, Ping P, Przyklenk K, Recchia FA, Schwartz Longacre L, Ripplinger CM, Van Eyk JE, Heusch G (2018) Guidelines for experimental models of myocardial ischemia and infarction. Am J Physiol Heart Circ Physiol 314:H812–H838. https://doi.org/10.1152/ajpheart.00335.2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lindsey ML, Kassiri Z, Virag JAI, de Castro Bras LE, Scherrer-Crosbie M (2018) Guidelines for measuring cardiac physiology in mice. Am J Physiol Heart Circ Physiol 314:H733–H752. https://doi.org/10.1152/ajpheart.00339.2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lindsey ML, Saucerman JJ, DeLeon-Pennell KY (2016) Knowledge gaps to understanding cardiac macrophage polarization following myocardial infarction. Biochim Biophys Acta 1862:2288–2292. https://doi.org/10.1016/j.bbadis.2016.05.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liu T, Shen D, Xing S, Chen J, Yu Z, Wang J, Wu B, Chi H, Zhao H, Liang Z, Chen C (2013) Attenuation of exogenous angiotensin II stress-induced damage and apoptosis in human vascular endothelial cells via microRNA-155 expression. Int J Mol Med 31:188–196. https://doi.org/10.3892/ijmm.2012.1182

    Article  CAS  PubMed  Google Scholar 

  39. Lu L, McCurdy S, Huang S, Zhu X, Peplowska K, Tiirikainen M, Boisvert WA, Garmire LX (2016) Time series miRNA-mRNA integrated analysis reveals critical miRNAs and targets in macrophage polarization. Sci Rep 6:37446. https://doi.org/10.1038/srep37446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ma Y, Mouton AJ, Lindsey ML (2018) Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction. Transl Res 191:15–28. https://doi.org/10.1016/j.trsl.2017.10.001

    Article  PubMed  Google Scholar 

  41. Marinkovic G, Heemskerk N, van Buul JD, de Waard V (2015) The ins and outs of small GTPase Rac1 in the vasculature. J Pharmacol Exp Ther 354:91–102. https://doi.org/10.1124/jpet.115.223610

    Article  CAS  PubMed  Google Scholar 

  42. Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6:13. https://doi.org/10.12703/P6-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mouton AJ, DeLeon-Pennell KY, Rivera Gonzalez OJ, Flynn ER, Freeman TC, Saucerman JJ, Garrett MR, Ma Y, Harmancey R, Lindsey ML (2018) Mapping macrophage polarization over the myocardial infarction time continuum. Basic Res Cardiol 113:26. https://doi.org/10.1007/s00395-018-0686-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Osada-Oka M, Shiota M, Izumi Y, Nishiyama M, Tanaka M, Yamaguchi T, Sakurai E, Miura K, Iwao H (2017) Macrophage-derived exosomes induce inflammatory factors in endothelial cells under hypertensive conditions. Hypertens Res 40:353–360. https://doi.org/10.1038/hr.2016.163

    Article  CAS  PubMed  Google Scholar 

  45. Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12:19–30. https://doi.org/10.1038/ncb2000(sup pp 11–13)

    Article  CAS  PubMed  Google Scholar 

  46. Panizzi P, Swirski FK, Figueiredo JL, Waterman P, Sosnovik DE, Aikawa E, Libby P, Pittet M, Weissleder R, Nahrendorf M (2010) Impaired infarct healing in atherosclerotic mice with Ly-6C(hi) monocytosis. J Am Coll Cardiol 55:1629–1638. https://doi.org/10.1016/j.jacc.2009.08.089

    Article  PubMed  PubMed Central  Google Scholar 

  47. Pankratz F, Bemtgen X, Zeiser R, Leonhardt F, Kreuzaler S, Hilgendorf I, Smolka C, Helbing T, Hoefer I, Esser JS, Kustermann M, Moser M, Bode C, Grundmann S (2015) MicroRNA-155 exerts cell-specific antiangiogenic but proarteriogenic effects during adaptive neovascularization. Circulation 131:1575–1589. https://doi.org/10.1161/CIRCULATIONAHA.114.014579

    Article  CAS  PubMed  Google Scholar 

  48. Podaru MN, Fields L, Kainuma S, Ichihara Y, Hussain M, Ito T, Kobayashi K, Mathur A, D'Acquisto F, Lewis-McDougall F, Suzuki K (2019) Reparative macrophage transplantation for myocardial repair: a refinement of bone marrow mononuclear cell-based therapy. Basic Res Cardiol 114:34. https://doi.org/10.1007/s00395-019-0742-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Richards J, Gabunia K, Kelemen SE, Kako F, Choi ET, Autieri MV (2015) Interleukin-19 increases angiogenesis in ischemic hind limbs by direct effects on both endothelial cells and macrophage polarization. J Mol Cell Cardiol 79:21–31. https://doi.org/10.1016/j.yjmcc.2014.11.002

    Article  CAS  PubMed  Google Scholar 

  50. Tang N, Sun B, Gupta A, Rempel H, Pulliam L (2016) Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-kappaB in endothelial cells. FASEB J 30:3097–3106. https://doi.org/10.1096/fj.201600368RR

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. ter Horst EN, Hakimzadeh N, van der Laan AM, Krijnen PA, Niessen HW, Piek JJ (2015) Modulators of macrophage polarization influence healing of the infarcted myocardium. Int J Mol Sci 16:29583–29591. https://doi.org/10.3390/ijms161226187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. van der Vorst EPC, Weber C (2019) Novel features of monocytes and macrophages in cardiovascular biology and disease. Arterioscler Thromb Vasc Biol 39:e30–e37. https://doi.org/10.1161/ATVBAHA.118.312002

    Article  CAS  PubMed  Google Scholar 

  53. Verderio C, Gabrielli M, Giussani P (2018) Role of sphingolipids in the biogenesis and biological activity of extracellular vesicles. J Lipid Res 59:1325–1340. https://doi.org/10.1194/jlr.R083915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wang C, Zhang C, Liu L, Axx X, Chen B, Li Y, Du J (2017) Macrophage-derived mir-155-containing exosomes suppress fibroblast proliferation and promote fibroblast inflammation during cardiac injury. Mol Ther 25:192–204. https://doi.org/10.1016/j.ymthe.2016.09.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Weber M, Kim S, Patterson N, Rooney K, Searles CD (2014) MiRNA-155 targets myosin light chain kinase and modulates actin cytoskeleton organization in endothelial cells. Am J Physiol Heart Circ Physiol 306:H1192–1203. https://doi.org/10.1152/ajpheart.00521.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Williams JW, Giannarelli C, Rahman A, Randolph GJ, Kovacic JC (2018) Macrophage biology, classification, and phenotype in cardiovascular disease: JACC macrophage in CVD series (Part 1). J Am Coll Cardiol 72:2166–2180. https://doi.org/10.1016/j.jacc.2018.08.2148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wu R, Gao W, Yao K, Ge J (2019) Roles of exosomes derived from immune cells in cardiovascular diseases. Front Immunol 10:648. https://doi.org/10.3389/fimmu.2019.00648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, Ofrecio JM, Wollam J, Hernandez-Carretero A, Fu W, Li P, Olefsky JM (2017) Adipose tissue macrophage-derived exosomal mirnas can modulate in vivo and in vitro insulin sensitivity. Cell 171(372–384):e312. https://doi.org/10.1016/j.cell.2017.08.035

    Article  CAS  Google Scholar 

  59. Yuan A, Hsiao YJ, Chen HY, Chen HW, Ho CC, Chen YY, Liu YC, Hong TH, Yu SL, Chen JJ, Yang PC (2015) Opposite effects of M1 and M2 macrophage subtypes on lung cancer progression. Sci Rep 5:14273. https://doi.org/10.1038/srep14273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zhang Y, Zhang M, Li X, Tang Z, Wang X, Zhong M, Suo Q, Zhang Y, Lv K (2016) Silencing microRNA-155 attenuates cardiac injury and dysfunction in viral myocarditis via promotion of M2 phenotype polarization of macrophages. Sci Rep 6:22613. https://doi.org/10.1038/srep22613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Zheng B, Yin WN, Suzuki T, Zhang XH, Zhang Y, Song LL, Jin LS, Zhan H, Zhang H, Li JS, Wen JK (2017) Exosome-mediated miR-155 transfer from smooth muscle cells to endothelial cells induces endothelial injury and promotes atherosclerosis. Mol Ther 25:1279–1294. https://doi.org/10.1016/j.ymthe.2017.03.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zheng P, Luo Q, Wang W, Li J, Wang T, Wang P, Chen L, Zhang P, Chen H, Liu Y, Dong P, Xie G, Ma Y, Jiang L, Yuan X, Shen L (2018) Tumor-associated macrophages-derived exosomes promote the migration of gastric cancer cells by transfer of functional apolipoprotein E. Cell Death Dis 9:434. https://doi.org/10.1038/s41419-018-0465-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhou J, Bai W, Liu Q, Cui J, Zhang W (2018) Intermittent hypoxia enhances THP-1 monocyte adhesion and chemotaxis and promotes M1 macrophage polarization via RAGE. Biomed Res Int 2018:1650456. https://doi.org/10.1155/2018/1650456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhu N, Zhang D, Chen S, Liu X, Lin L, Huang X, Guo Z, Liu J, Wang Y, Yuan W, Qin Y (2011) Endothelial enriched microRNAs regulate angiotensin II-induced endothelial inflammation and migration. Atherosclerosis 215:286–293. https://doi.org/10.1016/j.atherosclerosis.2010.12.024

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Letpub Inc. and Minghui Tan (Jinan University) for the help in Graphic illustration image (Fig. 9), as well as other members in the Guangzhou Institute of Cardiovascular Disease for helpful discussions and technical assistance.

Funding

This study was supported by research grants from National Natural Science Foundation of China (No. 81570259, 81873474, 81600350), Special Innovation Projects of Universities in Guangdong Province (No. 2018KTSCX189), Program of Construction of High Level Universities for Guangzhou Medical University (to Shi.L. and to Shao.L.), The Key Medical Disciplines and Specialties Program of Guangzhou (2017–2019).

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  1. Shaojun Liu, Jing Chen and Jian Shi have contributed equally to this article.

Authors and Affiliations

  1. Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People’s Republic of China

    Shaojun Liu, Jing Chen, Jian Shi, Wenyi Zhou, Li Wang, Weilun Fang, Yun Zhong, Yanfang Chen & Shiming Liu

  2. Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People’s Republic of China

    Li Wang, Yun Zhong & Shiming Liu

  3. Department of Emergency, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People’s Republic of China

    Xiaohui Chen

  4. Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH, 45435, USA

    Yanfang Chen

  5. Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, MERB 1045, 3500 N. Broad Street, Philadelphia, PA, 19140, USA

    Abdelkarim Sabri

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  1. Shaojun Liu
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Liu, S., Chen, J., Shi, J. et al. M1-like macrophage-derived exosomes suppress angiogenesis and exacerbate cardiac dysfunction in a myocardial infarction microenvironment. Basic Res Cardiol 115, 22 (2020). https://doi.org/10.1007/s00395-020-0781-7

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