| First Author | Rui T | Year | 2012 |
| Journal | Cardiovasc Res | Volume | 94 |
| Issue | 2 | Pages | 370-8 |
| PubMed ID | 22258632 | Mgi Jnum | J:198901 |
| Mgi Id | MGI:5499715 | Doi | 10.1093/cvr/cvs015 |
| Citation | Rui T, et al. (2012) Reduction in IL-33 expression exaggerates ischaemia/reperfusion-induced myocardial injury in mice with diabetes mellitus. Cardiovasc Res 94(2):370-8 |
| abstractText | AIMS: The underlying mechanism(s) of vulnerability of the diabetic myocardium to ischaemia/reperfusion (I/R)-induced injury is not fully understood. Interleukin-33 (IL-33) has been reported showing the beneficial effect to the 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 RESULTS: DM hearts were challenged with I/R in vivo, whereas 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 betaII (PKCbetaII) activation. Exogenous IL-33 prevented the DM-induced PKCbetaII activation and attenuated I/R injuries (myocardial infarction size and apoptosis). HG-conditioned myocytes incurred exaggerated apoptosis when compared with naive myocytes after A/R which was attenuated by IL-33. HG activated PKCbetaII in cardiomyocytes, which was further enhanced by A/R. IL-33 prevented the PKCbetaII activation in myocytes with HG or HG and A/R. Inhibition of PKCbetaII 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. CONCLUSION: Our results indicate that decreased levels of IL-33 are responsible for the increased sensitivity of the myocardium to I/R in DM. Reduction in IL-33 results in a chronic activation of PKCbetaII. I/R further enhances PKCbetaII activation in the diabetic myocardium which results in exaggeration of myocardial injury. |
