M2 Macrophage‐Derived sEV Regulate Pro‐Inflammatory CCR2+ Macrophage Subpopulations to Favor Post‐AMI Cardiac Repair
Abstract Tissue‐resident cardiac macrophage subsets mediate cardiac tissue inflammation and repair after acute myocardial infarction (AMI). CC chemokine receptor 2 (CCR2)‐expressing macrophages have phenotypical similarities to M1‐polarized macrophages, are pro‐inflammatory, and recruit CCR2+ circul...
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| Format: | Article |
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Wiley
2023-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202202964 |
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| author | Lan Li Jiasong Cao Sheng Li Tianyi Cui Jingyu Ni Han Zhang Yan Zhu Jingyuan Mao Xiumei Gao Adam C. Midgley Meifeng Zhu Guanwei Fan |
| author_facet | Lan Li Jiasong Cao Sheng Li Tianyi Cui Jingyu Ni Han Zhang Yan Zhu Jingyuan Mao Xiumei Gao Adam C. Midgley Meifeng Zhu Guanwei Fan |
| author_sort | Lan Li |
| collection | DOAJ |
| description | Abstract Tissue‐resident cardiac macrophage subsets mediate cardiac tissue inflammation and repair after acute myocardial infarction (AMI). CC chemokine receptor 2 (CCR2)‐expressing macrophages have phenotypical similarities to M1‐polarized macrophages, are pro‐inflammatory, and recruit CCR2+ circulating monocytes to infarcted myocardium. Small extracellular vesicles (sEV) from CCR2̶ macrophages, which phenotypically resemble M2‐polarized macrophages, promote anti‐inflammatory activity and cardiac repair. Here, the authors harvested M2 macrophage‐derived sEV (M2EV) from M2‐polarized bone‐marrow‐derived macrophages for intramyocardial injection and recapitulation of sEV‐mediated anti‐inflammatory activity in ischemic‐reperfusion (I/R) injured hearts. Rats and pigs received sham surgery; I/R without treatment; or I/R with autologous M2EV treatment. M2EV rescued cardiac function and attenuated injury markers, infarct size, and scar size. M2EV inhibited CCR2+ macrophage numbers, reduced monocyte‐derived CCR2+ macrophage recruitment to infarct sites, induced M1‐to‐M2 macrophage switching and promoted neovascularization. Analysis of M2EV microRNA content revealed abundant miR‐181b‐5p, which regulated macrophage glucose uptake, glycolysis, and mitigated mitochondrial reactive oxygen species generation. Functional blockade of miR‐181b‐5p is detrimental to beneficial M2EV actions and resulted in failure to inhibit CCR2+ macrophage numbers and infarct size. Taken together, this investigation showed that M2EV rescued myocardial function, improved myocardial repair, and regulated CCR2+ macrophages via miR‐181b‐5p‐dependent mechanisms, indicating an option for cell‐free therapy for AMI. |
| format | Article |
| id | doaj-art-61c7a69b309949ab967fa1c75e9c0e4c |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-61c7a69b309949ab967fa1c75e9c0e4c2025-08-20T04:01:01ZengWileyAdvanced Science2198-38442023-05-011014n/an/a10.1002/advs.202202964M2 Macrophage‐Derived sEV Regulate Pro‐Inflammatory CCR2+ Macrophage Subpopulations to Favor Post‐AMI Cardiac RepairLan Li0Jiasong Cao1Sheng Li2Tianyi Cui3Jingyu Ni4Han Zhang5Yan Zhu6Jingyuan Mao7Xiumei Gao8Adam C. Midgley9Meifeng Zhu10Guanwei Fan11State Key Laboratory of Modern Chinese Medicine Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education Tianjin University of Traditional Chinese Medicine Tianjin 301617 ChinaTianjin Key Laboratory of Human Development and Reproductive Regulation Tianjin Central Hospital of Gynecology Obstetrics Tianjin 300052 ChinaState Key Laboratory of Modern Chinese Medicine Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education Tianjin University of Traditional Chinese Medicine Tianjin 301617 ChinaState Key Laboratory of Modern Chinese Medicine Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education Tianjin University of Traditional Chinese Medicine Tianjin 301617 ChinaState Key Laboratory of Modern Chinese Medicine Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education Tianjin University of Traditional Chinese Medicine Tianjin 301617 ChinaState Key Laboratory of Modern Chinese Medicine Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education Tianjin University of Traditional Chinese Medicine Tianjin 301617 ChinaState Key Laboratory of Modern Chinese Medicine Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education Tianjin University of Traditional Chinese Medicine Tianjin 301617 ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion State Key Laboratory of Component‐based Chinese Medicine First Teaching Hospital of Tianjin University of Traditional Chinese Medicine Tianjin 300193 ChinaState Key Laboratory of Modern Chinese Medicine Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education Tianjin University of Traditional Chinese Medicine Tianjin 301617 ChinaKey Laboratory of Bioactive Materials for the Ministry of Education College of Life Sciences Nankai University Tianjin 300071 ChinaKey Laboratory of Bioactive Materials for the Ministry of Education College of Life Sciences Nankai University Tianjin 300071 ChinaState Key Laboratory of Modern Chinese Medicine Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education Tianjin University of Traditional Chinese Medicine Tianjin 301617 ChinaAbstract Tissue‐resident cardiac macrophage subsets mediate cardiac tissue inflammation and repair after acute myocardial infarction (AMI). CC chemokine receptor 2 (CCR2)‐expressing macrophages have phenotypical similarities to M1‐polarized macrophages, are pro‐inflammatory, and recruit CCR2+ circulating monocytes to infarcted myocardium. Small extracellular vesicles (sEV) from CCR2̶ macrophages, which phenotypically resemble M2‐polarized macrophages, promote anti‐inflammatory activity and cardiac repair. Here, the authors harvested M2 macrophage‐derived sEV (M2EV) from M2‐polarized bone‐marrow‐derived macrophages for intramyocardial injection and recapitulation of sEV‐mediated anti‐inflammatory activity in ischemic‐reperfusion (I/R) injured hearts. Rats and pigs received sham surgery; I/R without treatment; or I/R with autologous M2EV treatment. M2EV rescued cardiac function and attenuated injury markers, infarct size, and scar size. M2EV inhibited CCR2+ macrophage numbers, reduced monocyte‐derived CCR2+ macrophage recruitment to infarct sites, induced M1‐to‐M2 macrophage switching and promoted neovascularization. Analysis of M2EV microRNA content revealed abundant miR‐181b‐5p, which regulated macrophage glucose uptake, glycolysis, and mitigated mitochondrial reactive oxygen species generation. Functional blockade of miR‐181b‐5p is detrimental to beneficial M2EV actions and resulted in failure to inhibit CCR2+ macrophage numbers and infarct size. Taken together, this investigation showed that M2EV rescued myocardial function, improved myocardial repair, and regulated CCR2+ macrophages via miR‐181b‐5p‐dependent mechanisms, indicating an option for cell‐free therapy for AMI.https://doi.org/10.1002/advs.202202964CC chemokine receptor 2extracellular vesiclesischemia‐reperfusion injurymacrophage metabolic reprogrammingmacrophages |
| spellingShingle | Lan Li Jiasong Cao Sheng Li Tianyi Cui Jingyu Ni Han Zhang Yan Zhu Jingyuan Mao Xiumei Gao Adam C. Midgley Meifeng Zhu Guanwei Fan M2 Macrophage‐Derived sEV Regulate Pro‐Inflammatory CCR2+ Macrophage Subpopulations to Favor Post‐AMI Cardiac Repair Advanced Science CC chemokine receptor 2 extracellular vesicles ischemia‐reperfusion injury macrophage metabolic reprogramming macrophages |
| title | M2 Macrophage‐Derived sEV Regulate Pro‐Inflammatory CCR2+ Macrophage Subpopulations to Favor Post‐AMI Cardiac Repair |
| title_full | M2 Macrophage‐Derived sEV Regulate Pro‐Inflammatory CCR2+ Macrophage Subpopulations to Favor Post‐AMI Cardiac Repair |
| title_fullStr | M2 Macrophage‐Derived sEV Regulate Pro‐Inflammatory CCR2+ Macrophage Subpopulations to Favor Post‐AMI Cardiac Repair |
| title_full_unstemmed | M2 Macrophage‐Derived sEV Regulate Pro‐Inflammatory CCR2+ Macrophage Subpopulations to Favor Post‐AMI Cardiac Repair |
| title_short | M2 Macrophage‐Derived sEV Regulate Pro‐Inflammatory CCR2+ Macrophage Subpopulations to Favor Post‐AMI Cardiac Repair |
| title_sort | m2 macrophage derived sev regulate pro inflammatory ccr2 macrophage subpopulations to favor post ami cardiac repair |
| topic | CC chemokine receptor 2 extracellular vesicles ischemia‐reperfusion injury macrophage metabolic reprogramming macrophages |
| url | https://doi.org/10.1002/advs.202202964 |
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