Beclin-1 overexpression regulates NLRP3 activation by promoting TNFAIP3 in microvascular injury following myocardial reperfusion |
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Institution: | 1. Department of Physiology—HeartOtago, University of Otago, New Zealand;2. School of Clinical Sciences, Bristol Heart Institute, University of Bristol, Bristol, United Kingdom;3. Department of Cardiovascular Surgery, University of Otago, New Zealand;4. Department of Anatomy, University of Otago, New Zealand;5. Department of Surgery, University of Otago, New Zealand;1. Department of Cardiology, The Second Affiliated Hospital, Kunming Medical University, Kunming 650101, China;2. Department of Anatomy and Histology, School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China;3. Technology Transfer Center, Kunming Medical University, Kunming 650500, China |
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Abstract: | Innate immune response contributes significantly to ischemia reperfusion (I/R) injury. Targeting innate immunity seems to be a promising method for protecting the microvascular injury in ST-elevation myocardial infarction (STEMI) patients following myocardial I/R injury (MI/R). NLRP3 inflammasome is a central part of the innate immune system involved in the pathophysiological process of MI/R. However, the mechanisms regulating NLRP3 activation are yet to be clarified. Recently, autophagy has been related to the regulation of NLRP3 activation. Thus, how Beclin-1/Becn1 overexpression influences NLRP3 activation in microvascular endothelial cells (CMECs) after MI/R is yet to be investigated. The present study showed that Becn1 overexpression exhibits a significant increase in NLRP3 and IL-1β in CMEC responses to MI/R. Interestingly, Becn1 overexpression promoted TNFAIP3 expression, which restricted NLRP3 activation in vitro and in vivo. The current study also showed that inflammatory cells (CD68) and B (CDB220) lymphocytes were decreased in transgenic mice with overexpression of Beclin-1 (BECN1-Tg) in the spleen and heart. These findings highlighted Becn1 as a prospective target for treating NLRP3 mediated microvascular injury following MI/R. |
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