Participation of Heart Mitochondria in Myocardial Protection Against Ischemia/Reperfusion Injury: Benefit Effects of Short-Term Adaptation Processes

Abstract

Acute streptozotocin diabetes mellitus (DM) as well as remote ischemic preconditioning (RPC) has shown a favorable effect on the postischemic-reperfusion function of the myocardium. Cardioprotective mechanisms offered by these experimental models involve the mitochondria with the changes in functional properties of membrane as the end-effector. The aim was to find out whether separate effects of RPC and DM would stimulate the mechanisms of cardioprotection to a maximal level or whether RPC and DM conditions would cooperate in stimulation of cardioprotection. Experiments were performed on male Wistar rats divided into groups: control, DM, RPC and DM treated by RPC (RPC+DM). RPC protocol of 3 cycles of 5-min hind limb ischemia followed by 5-min reperfusion was used. Ischemicreperfusion injury was induced by 30-min ischemia followed by 40-min reperfusion of the hearts in Langendorff mode. Mitochondria were isolated by differential centrifugation, infarct size assessed by staining with 1 % 2,3,5-triphenyltetrazolium chloride, mitochondrial membrane fluidity with a fluorescent probe DPH, CoQ 9 and CoQ10 with HPLC. Results revealed that RPC as well as DM decreased the infarct size and preserved mitochondrial function by increasing the mitochondrial membrane fluidity. Both used models separately offered a sufficient protection against ischemic-reperfusion injury without an additive effect of their combination.

Deciphering the Protein, Modular Connections and Precision Medicine for Heart Failure With Preserved Ejection Fraction and Hypertension Based on TMT Quantitative Proteomics and Molecular Docking

“…This suggests that Hp could be used to diagnose HTN and HFpEF and that Hp could be an effective therapeutic target for HTN and HFpEF. COQ9 is involved in the basic functions of mitochondria ( Ferko et al, 2015 ), and the impairment of mitochondrial function is a common pathophysiological mechanism underlying both HTN and HFpEF ( He et al, 2019 ; Zeng and Chen, 2019 ). Thus, COQ9 is also a potential biomarker for HTN and HFpEF.…”

Cardioprotection Induced by Remote Ischemic Preconditioning Preserves the Mitochondrial Respiratory Function in Acute Diabetic Myocardium

“…Several studies have investigated various effect of IPC in the context of the inhibition of mitochondrial respiratory chain in the presence of NADH-linked substrates (da Silva et al 2003), the increase of basal state of mitochondrial respiration (Liem et al 2008) and the improving of mitochondrial state 3 respiration during reperfusion (Crestanello et al 2002). Although the most of physiological parameters, including myocardial infarct size, were reported to be ameliorated after application of RPC (Ferko et al 2015, Zhu et al 2013, we did not observe improvement in mitochondrial respiratory function corresponding to the earlier study (Ferko et al 2014). However, data from absorption spectrophotometry suggest that RPC prevented the decrease of ATP synthase activity after ischemia-reperfusion and that this contributed to the preservation of mitochondrial function following I/R injury.…”

“…However, despite these positive findings, the actual role of mitochondrial bioenergetics in the myocardial protection conveyed by RPC and DM is still elusive. There is some evidence that the immediate protection by RPC might involve a preservation of mitochondrial state 3 respiration (Ferko et al 2014) and, at the combined intervention of RPC and DM, the preservation of mitochondrial function is associated with an increase in the mitochondrial membrane fluidity (Ferko et al 2015). Perhaps, the most prompting experimental task is to elucidate the nature of the model interaction that would result in the protective effect on the myocardiumwhether it is additive, synergistic or antagonistic.…”

Emerging role of non-coding RNAs and extracellular vesicles in cardioprotection by remote ischemic conditioning of the heart

“…In these studies, cardioprotection was evoked by ischemic insults from different distant organs including the kidney (Diwan et al, 2008;Kant et al, 2008;Lang et al, 2006;Takaoka et al, 1999;Weinbrenner et al, 2002), small intestine (Gho et al, 1996;Schoemaker and van Heijningen, 2000), and liver (Barteková et al, 2003(Barteková et al, , 2004. Moreover, RIC is also induced by limitation of blood flow in the extremities (Birnbaum et al, 1997;Ferko et al, 2015;Oxman et al, 1997;Sharma et al, 2016), which seems to have potentially the highest relevance for use in humans (Kharbanda et al, 2001). For the purpose of developing pharmacological mimetics of RIC to maximize its clinical applicability, it is essential to uncover molecules that act as key players in cardioprotection afforded by RIC.…”