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