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.

Aims

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

Methods and results

We investigated cardiac structure and function (assessed by TTE) of OPA1+/– 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+/– 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+/– 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+/– mice suggesting an alteration of sarcoplasmic reticulum calcium capacity uptake.

Conclusion

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.

The author hereby declares no conflict of interest