Platelet-derived extracellular vesicles encapsulate microRNA-34c-5p to ameliorate inflammatory response of coronary artery endothelial cells via PODXL-mediated P38 MAPK signaling pathway |
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| Affiliation: | 1. Department of Anaesthesiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, PR China;2. Department of Clinical Laboratory, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, PR China;1. IRCCS Istituto Auxologico Italiano, Cardiology Department, St Luca Hospital, Piazza Brescia Milan, Italy;2. Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy;1. Health Management Center, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China;2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China;3. Department of Gynecology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China;4. Department of Nursing, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China;1. Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy;2. Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy;3. National Centre for Healthcare Research & Pharmacoepidemiology, at the University of Milano-Bicocca, Milan, Italy;4. Laboratory of Healthcare Research & Pharmacoepidemiology, Unit of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy;1. Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan, 430030, China;2. Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan, 430030, China;3. Department of Cardiology, Kailuan Hospital, North China University of Science and Technology, No.57 Xinhua East Road, Tangshan City, 063001, China;4. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No.38 Xueyuan Road, Beijing, 100191, China;1. School of Medical Sciences, UNSW Sydney, Sydney, NSW 2052, Australia;2. Garvan Institute of Medical Research, St Vincent''s Clinical School, UNSW Sydney, Sydney, NSW 2010, Australia;3. The Institute of Hepatology, Foundation for Liver Research, London, UK;4. Faculty of Life Sciences and Medicine, King''s College London, London, UK;1. Pediatrics, Turkish Ministry of Health Ankara City Hospital, Bilkent, Ankara, Turkey;2. Department of Biostatistics, Cukurova University, Adana, Turkey;3. Pediatrics, Ankara Training and Research Hospital, Ankara, Turkey;4. Pediatrics, Baskent University Hospital, Ankara, Turkey |
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| Abstract: | Background and aimsLow-grade chronic inflammation was reported to serve as a distinctive pathophysiologic feature of coronary artery disease (CAD), the leading cause of death around the world. Herein, the current study aimed to explore whether and how microRNA-34c-5p (miR-34c-5p), a miRNA enriched in extracellular vesicles (EVs) originated from the activated platelet (PLT-EVs), affects the inflammation of human coronary artery endothelial cells (HCAECs).Methods and resultsHCAECs were established as an in vitro cell model using oxidized low-density lipoprotein (ox-LDL). miR-34c-5p, an abundant miRNA in PLT-EVs, can be transferred to HCAECs and target PODXL by binding to its 3′UTR. Gain- and loss-of-function experiments of miR-34c-5p and podocalyxin (PODXL) were performed in ox-LDL-induced HCAECs. Subsequently, HCAECs were subjected to co-culture with PLT-EVs, followed by detection of the expression patterns of key pro-inflammatory factors. Either miR-34c-5p mimic or PLT-EVs harboring miR-34c-5p attenuated the ox-LDL-evoked inflammation in HCAECs by suppressing interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). By blocking the P38 MAPK signaling pathway, miR-34c-5p-mediated depletion of PODXL contributed to protection against ox-LDL-induced inflammation. In vitro findings were further validated by findings observed in ApoE knock-out mice. Additionally, miR-34c-5p in PLT-EVs showed an athero-protective role in the murine model.ConclusionAltogether, our findings highlighted that miR-34c-5p in PLT-EVs could alleviate inflammation response in HCAECs by targeting PODXL and inactivation of the P38 MAPK signaling pathway. |
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| Keywords: | Atherosclerosis Platelet Extracellular vesicles microRNA-34c-5p Human coronary artery endothelial cells Inflammation P38 MAPK pathway |
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