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Article: Activation of autophagy inhibits nucleotide‐binding oligomerization domain‐like receptor protein 3 inflammasome activation and attenuates myocardial ischemia‐reperfusion injury in diabetic rats

TitleActivation of autophagy inhibits nucleotide‐binding oligomerization domain‐like receptor protein 3 inflammasome activation and attenuates myocardial ischemia‐reperfusion injury in diabetic rats
Authors
KeywordsDiabetic myocardium
Myocardial ischemia‐reperfusion injury
Nucleotide‐binding oligomerization domain‐like receptor protein 3 inflammasome
Issue Date2020
PublisherWiley Open Access: Various Creative Commons Licenses. The Journal's web site is located at https://onlinelibrary.wiley.com/journal/20401124
Citation
Journal of Diabetes Investigation, 2020, v. 11 n. 5, p. 1126-1136 How to Cite?
AbstractAims/Introduction Diabetic hearts are more vulnerable to ischemia‐reperfusion injury (I/RI). The activation of nucleotide‐binding oligomerization domain‐like receptor protein 3 (NLRP3) inflammasome can mediate the inflammatory process, and hence might contribute to myocardial I/RI. Activation of autophagy can eliminate excess reactive oxygen species and alleviate myocardial I/RI in diabetes. The present study aimed to investigate whether the activation of autophagy can alleviate diabetic myocardial I/RI through inhibition of NLRP3 inflammasome activation. Materials and Methods A dose of 65 mg/kg streptozotocin was given by tail vein injection to establish a type 1 diabetes model in the rats. The left anterior descending coronary artery was ligated for 30 min followed by reperfusion for 2 h to establish a myocardial I/RI model. H9C2 cardiomyocytes were exposed to high glucose (33 mmol/L) and subjected to hypoxia–reoxygenation (6 h hypoxia followed by 4 h reoxygenation). Results The diabetic rats showed significant inhibition of cardiac autophagy (decreased LC3‐II/I and increased p62) that was concomitant with increased activation of NLRP3 inflammasome (increased NLRP3, apoptosis‐related spots protein cleaved caspase‐1, interleukin‐18, interleukin‐1β) and more severe myocardial I/RI (elevated creatine kinase myocardial band, lactate dehydrogenase and larger infarct size). However, administration of rapamycin, an inhibitor of the autophagy, to activate autophagy resulted in the inhibition of NLRP3 inflammasome, and finally alleviated myocardial I/RI. In vitro, high glucose inhibited autophagy, while activating NLRP3 inflammasome in H9C2 cardiomyocytes and aggravating hypoxia–reoxygenation injury, but rapamycin reversed these adverse effects of high glucose. Conclusion Activation of autophagy can suppress the formation of NLRP3 inflammasome, which in turn attenuates myocardial ischemia‐reperfusion injury in diabetic rats.
Persistent Identifierhttp://hdl.handle.net/10722/293247
ISSN
2019 Impact Factor: 3.761
2015 SCImago Journal Rankings: 0.964
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, D-
dc.contributor.authorHe, Y-
dc.contributor.authorYe, X-
dc.contributor.authorCai, Y-
dc.contributor.authorXu, J-
dc.contributor.authorZhang, L-
dc.contributor.authorLi, M-
dc.contributor.authorLiu, H-
dc.contributor.authorWang, S-
dc.contributor.authorXia, Z-
dc.date.accessioned2020-11-23T08:13:58Z-
dc.date.available2020-11-23T08:13:58Z-
dc.date.issued2020-
dc.identifier.citationJournal of Diabetes Investigation, 2020, v. 11 n. 5, p. 1126-1136-
dc.identifier.issn2040-1116-
dc.identifier.urihttp://hdl.handle.net/10722/293247-
dc.description.abstractAims/Introduction Diabetic hearts are more vulnerable to ischemia‐reperfusion injury (I/RI). The activation of nucleotide‐binding oligomerization domain‐like receptor protein 3 (NLRP3) inflammasome can mediate the inflammatory process, and hence might contribute to myocardial I/RI. Activation of autophagy can eliminate excess reactive oxygen species and alleviate myocardial I/RI in diabetes. The present study aimed to investigate whether the activation of autophagy can alleviate diabetic myocardial I/RI through inhibition of NLRP3 inflammasome activation. Materials and Methods A dose of 65 mg/kg streptozotocin was given by tail vein injection to establish a type 1 diabetes model in the rats. The left anterior descending coronary artery was ligated for 30 min followed by reperfusion for 2 h to establish a myocardial I/RI model. H9C2 cardiomyocytes were exposed to high glucose (33 mmol/L) and subjected to hypoxia–reoxygenation (6 h hypoxia followed by 4 h reoxygenation). Results The diabetic rats showed significant inhibition of cardiac autophagy (decreased LC3‐II/I and increased p62) that was concomitant with increased activation of NLRP3 inflammasome (increased NLRP3, apoptosis‐related spots protein cleaved caspase‐1, interleukin‐18, interleukin‐1β) and more severe myocardial I/RI (elevated creatine kinase myocardial band, lactate dehydrogenase and larger infarct size). However, administration of rapamycin, an inhibitor of the autophagy, to activate autophagy resulted in the inhibition of NLRP3 inflammasome, and finally alleviated myocardial I/RI. In vitro, high glucose inhibited autophagy, while activating NLRP3 inflammasome in H9C2 cardiomyocytes and aggravating hypoxia–reoxygenation injury, but rapamycin reversed these adverse effects of high glucose. Conclusion Activation of autophagy can suppress the formation of NLRP3 inflammasome, which in turn attenuates myocardial ischemia‐reperfusion injury in diabetic rats.-
dc.languageeng-
dc.publisherWiley Open Access: Various Creative Commons Licenses. The Journal's web site is located at https://onlinelibrary.wiley.com/journal/20401124-
dc.relation.ispartofJournal of Diabetes Investigation-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectDiabetic myocardium-
dc.subjectMyocardial ischemia‐reperfusion injury-
dc.subjectNucleotide‐binding oligomerization domain‐like receptor protein 3 inflammasome-
dc.titleActivation of autophagy inhibits nucleotide‐binding oligomerization domain‐like receptor protein 3 inflammasome activation and attenuates myocardial ischemia‐reperfusion injury in diabetic rats-
dc.typeArticle-
dc.identifier.emailCai, Y: caidavid@hku.hk-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityXia, Z=rp00532-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1111/jdi.13235-
dc.identifier.pmid32064785-
dc.identifier.pmcidPMC7477534-
dc.identifier.scopuseid_2-s2.0-85082491458-
dc.identifier.hkuros319118-
dc.identifier.volume11-
dc.identifier.issue5-
dc.identifier.spage1126-
dc.identifier.epage1136-
dc.identifier.isiWOS:000522069400001-
dc.publisher.placeAustralia-
dc.identifier.issnl2040-1116-

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