| Reduction of IL-33 expression exaggerates ischemia/reperfusion-induced myocardial injury in mice with Diabetes Mellitus. | |
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MedLine Citation:
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PMID: 22258632 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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AIMS: The underlying mechanism(s) of vulnerability of diabetic myocardium to ischemia/reperfusion (I/R)-induced injury is not fully understood. Interleukin 33 (IL-33) has been reported showing beneficial effect to myocardium on I/R injury. The aims of this study were to test whether diabetes mellitus (DM) affects myocardial levels of IL-33 and to examine whether reduction in IL-33 is responsible for exaggerated I/R injury in the diabetic myocardium.Methods and ResultsDM hearts were challenged with an I/R in vivo; while isolated cardiomyocytes in vitro were conditioned with high glucose (HG) followed by an anoxia/reoxygenation (A/R) challenge. Myocardial levels of IL-33 were decreased in mice with DM which was associated with increased protein kinase C βII (PKC βII) activation. Exogenous IL-33 prevented the DM-induced PKCβII activation, attenuated I/R injuries (myocardial infarction size and apoptosis). HG-conditioned myocytes incurred exaggerated apoptosis as compared to naïve myocytes after A/R which was attenuated by IL-33. HG activated PKCβII in cardiomyocytes, which was further enhanced by A/R. IL-33 prevented the PKCβII activation in myocytes with HG or HG and A/R. Inhibition of PKCβII prevented the beneficial effect of IL-33. Finally, IL-33 up-regulated diacylglycerol kinase zeta (DGK-zeta) in cardiomyocytes and reversed the down regulation of myocardial DGK-zeta in mice with DM. CONCLUSIONS: Our results indicate that decreased levels of IL-33 are responsible for the increased sensitivity of myocardium to I/R in DM. Reduction of IL-33 results in a chronic activation of PKCβII. I/R further enhances PKCβII activation in diabetic myocardium which results in exaggeration of myocardial injury. |
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Authors:
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Tao Rui; Jinchao Zhang; Xuemei Xu; Yongwei Yao; Raymond Kao; Claudio M Martin |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-18 |
Journal Detail:
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Title: Cardiovascular research Volume: - ISSN: 1755-3245 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Cardiology, Department of Medicine, the Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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