PMID- 36317904 OWN - NLM STAT- MEDLINE DCOM- 20221103 LR - 20221103 IS - 1522-6662 (Electronic) IS - 1098-3511 (Linking) VI - 25 IP - 5 DP - 2022 Sep 28 TI - M2 Macrophage-Derived Exosomes Regulate Myocardial Ischemia-Reperfusion And Pyroptosis Via ROS/NLRP3 Pathway. PG - E698-E708 LID - 10.1532/hsf.4919 [doi] AB - OBJECTIVE: To evaluate whether M2 macrophage-derived exosomes protect against MI/R injury and reveal the protective mechanism of exosomes [Kourembanas 2015]. METHODS: I/R model injury was induced by temporary left anterior descending coronary artery occlusion in Sprague-Dawley (SD) rats, macrophages isolated from bone marrow-derived macrophages (BMDMs) were induced to M2 polarization, and H9C2 cells subjected to hypoxia/reperfusion (H/R) were used to establish an in vitro model. I/R-induced rats and H/R-induced H9C2 cells were treated with M2-exos in vivo and in vitro, respectively. Masson staining was performed to observe myocardial fibrosis in rats. Immunohistochemical (IHC) staining of myocardial tissues showed the expression of NLRP3 inflammasome activation and pyrolysis. Exosomes derived from IL-4-treated macrophages (M2-exos) were detected by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western bolt. Western bolt was performed to determine the protein level, including NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1beta, cleaved IL-1beta, gasdermin D (GSDMD), and N-terminus of gasdermin D (GSDMD-N). RESULTS: Activity of NLRP3 inflammasome and existence of pyroptosis in the rats subjected to MI/R were significantly higher than those in the control (P < 0.05). Moreover, we confirmed the accumulation of ROS during I/R injury in cardiomyocytes. M2-exos protected against I/R injury and reduced activity of NLRP3 inflammasome and existence of pyroptosis, accompanied with attenuating oxidative stress. In vitro studies showed similar effects, H9c2 cells co-cultured with M2-exos could attenuated H/R-induced cell injury, while M2-exos suppressed the expression of NLRP3 inflammasome and pyroptosis (P < 0.05). FAU - Hu, Hui AU - Hu H AD - Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China. huhui1216@126.com. FAU - Qi, Lei AU - Qi L AD - Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China. 530428531@qq.com. FAU - Ren, Changjie AU - Ren C AD - Department of Cardiology, Jining No.1 People's Hospital, Jining, Shandong Province, China. renchangjie@medmailm.cn. FAU - Yan, Suhua AU - Yan S AD - Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan. yan_suhua5487@21cn.com. LA - eng PT - Journal Article DEP - 20220928 PL - United States TA - Heart Surg Forum JT - The heart surgery forum JID - 100891112 RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Inflammasomes) RN - 0 (Reactive Oxygen Species) RN - 0 (Nlrp3 protein, rat) SB - IM MH - Rats MH - Animals MH - Pyroptosis MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Inflammasomes/metabolism/pharmacology MH - Reactive Oxygen Species/metabolism/pharmacology MH - *Myocardial Reperfusion Injury/metabolism MH - *Exosomes/metabolism MH - Rats, Sprague-Dawley MH - Reperfusion MH - Macrophages/metabolism EDAT- 2022/11/02 06:00 MHDA- 2022/11/04 06:00 CRDT- 2022/11/01 09:04 PHST- 2022/06/06 00:00 [received] PHST- 2022/06/28 00:00 [accepted] PHST- 2022/11/01 09:04 [entrez] PHST- 2022/11/02 06:00 [pubmed] PHST- 2022/11/04 06:00 [medline] AID - 10.1532/hsf.4919 [doi] PST - epublish SO - Heart Surg Forum. 2022 Sep 28;25(5):E698-E708. doi: 10.1532/hsf.4919.