0296 : The human OPA1delTTAG mutation increases cardiac ischemiareperfusion injuries in mouse

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• 作者：Sophie Le Page¹ ; ^{sophie.le.page@wanadoo.fr" class="auth_mail" title="E-mail the corresponding author} ; Marjorie Niro¹ ; Laura Cellier² ; Abdallah Gharib³ ; Jé ; ré ; my Fauconnier⁴ ; Sophie Tamareille² ; Arnaud Chevrollier² ; Laurent Loufrani² ; Celine Grenier² ; Emmanuelle Sarzi⁵ ; Alain Lacampagne⁴ ; Michel Ovize³ ; Guy Lenaers² ; Daniel Henrion² ; Delphine Mirebeau-Prunier¹ ; Fabrice Prunier¹
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：8
• 期：3
• 页码：221
• 全文大小：50 K

文摘

Mitochondrial dynamics have been involved in cardiovascular diseases, particularly in ischemia-reperfusion process. While excessive mitochondrial fission has been described as pejorative, the role of fusion proteins (OPA1, MFN2) in this context remains uncertain.

d="absSec_2">Aims

d="spar0010">To determine the effects of OPA1 (protein implicated in mitochondrial inner membrane fusion) deficiency on cardiac ischemia-reperfusion (I/R) injury.

d="absSec_3">Methods and results

d="spar0020">We investigated cardiac structure and function (assessed by TTE) of OPA1+/&ndash; mutant mice (50% of OPA1 expression decreasing) and found that they displayed a significant alteration of left ventricular systolic function at 6 months, but were similar to Wild-type (WT) at 3 months. 3-month-old OPA1+/&ndash; mutant mice and theirs controls were then submitted to I/R in vivo (coronary artery ligature during 45 min/ 2h reperfusion) and ex vivo (30 min of global ischemia / 2h reperfusion). In vivo, infarct size was significantly higher in OPA1+/&ndash; mutant mice compared to WT group (43.2±4.1% vs. 28.4±3.5% respectively; p<0.01). Same results were observed in Langendorff model (71.1±3.2% vs. 59.6±8.5% respectively; p<0.05). No difference was observed in fission/fusion proteins expression, oxidative phosphorylation, apoptotic markers or mPTP function between mutant mice and WT after I/R. However, calcium transients were significantly lower in OPA1+/&ndash; mice suggesting an alteration of sarcoplasmic reticulum calcium capacity uptake.

d="absSec_4">Conclusion

d="spar0025">Deficiency in the fusion protein OPA1 was associated with higher susceptibility to myocardial I/R injury. Physiopathological mechanisms seem to involve calcium transients modulation, but need further explorations.

d="spar1005">The author hereby declares no conflict of interest