Remote Ischemic Conditioning Influences Mitochondrial Dynamics

Abstract

Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy to protect the heart against ischemia-reperfusion (I/R) injury. The mechanisms by which remote ischemic conditioning (RIC) is protective are to date unknown, yet a well-accepted theory holds that the mitochondria play a central role. Mitochondria are dynamic organelles that undergo fusion and fission. Interventions that decrease mitochondrial fission or increase mitochondrial fusion have been associated with reduced I/R injury. However, whether RIPC influences mitochondrial dynamics or not has yet to be ascertained.We sought to determine the role played by mitochondrial dynamics in RIPC-induced cardioprotection. Male adult rats exposed in vivo to myocardial I/R were assigned to one of two groups, either undergoing 40 min of myocardial ischemia followed by 120 min of reperfusion (MI group) or four 5-min cycles of limb ischemia interspersed by 5 min of limb reperfusion, immediately prior to myocardial ischemia and 120 min of reperfusion (MI+RIPC group). After reperfusion, infarct size was assessed and myocardial tissue was analyzed by Western blot and electron microscopy. RIPC induced smaller infarct size (-28%), increased mitochondrial fusion protein OPA1, and preserved mitochondrial morphology. These findings suggest that mitochondrial dynamics play a role in the mechanisms of RIPC-induced cardioprotection.

Unique morphological characteristics of mitochondrial subtypes in the heart: the effect of ischemia and ischemic preconditioning

“…Moreover, preservation of mitochondrial morphology via IPC has been previously shown to confer cardioprotection in the setting of IRI 11,38–40 . Although IPC has been suggested to preserve the function of SSM mitochondria following IR, we did not observe any IPC-induced preservation of SSM mitochondria morphology following ischemia-only treatment 30,31 .…”

Novel insights into the role of mitochondrial fusion and fission in cardiomyocyte apoptosis induced by ischemia/reperfusion

“…It is confirmed that I/R down‐regulates the expression of mitochondrial fusion proteins including Mfn1, Mfn2, and Opa1, disrupts mitochondrial fusion and increases cardiomyocyte apoptosis (Cellier et al, ; Dong, Chen, et al, ; Yang et al, ; Yu et al, , ; Zhao et al, ). Multiple lines of evidence suggest that inhibition of endogenous fusion proteins enhances I/R‐induced cardiomyocyte apoptosis, and up‐regulation of fusion proteins suppresses I/R‐induced cardiomyocyte apoptosis.…”

Mitochondrial-Shaping Proteins in Cardiac Health and Disease – the Long and the Short of It!

“…The studies also identified Mfn2 as a novel target of SIRT1 in which SIRT1 deacetylates Mfn2 to mediate autophagy induction [212, 213]. Male adult rats exposed to four 5-min cycles of limb ischemia interspersed by 5 min of limb reperfusion, immediately prior to myocardial ischemia and 120 min of reperfusion (MI + RIPC group) experienced a smaller infarct size (−28%), increased mitochondrial fusion protein OPA1, and preserved mitochondrial morphology [214]. A mild overexpression of OPA1 also protected against cardiac ischemic injury measured in the form of reduced LDH release in 5 months old mice subjected to a Langendorff model of 40 min of ischemia followed by 15 min of reperfusion [215].…”

“…Remote ischemic preconditioning (RIPC) has been shown to induce upregulation of OPA1 [214], and sevoflurane postconditioning has been reported to suppress the decline of OPA1 and increase in f Drp1 and Parkin induced by IRI [234]. …”