Vagal nerve stimulation prevents reperfusion injury through inhibition of opening of mitochondrial permeability transition pore independent of the bradycardiac effect

Katare, Rajesh; Ando, Motonori; Kakinuma, Yoshihiko; Arikawa, Mikihiko; Handa, Takemi; Yamasaki, Fumiyasu; Sato, Takayuki

doi:10.1016/j.jtcvs.2008.08.020

Cited by 122 publications

(90 citation statements)

References 28 publications

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“…42,43 Moreover, the concentration of by guest on May 11, 2018 http://atvb.ahajournals.org/ Downloaded from acetylcholine for therapy in the pathological conditions is usually higher than the physiological level. 40,44 In the present study, treatment with acetylcholine (10…”

Section: Discussionmentioning

confidence: 79%

Reduction of Mitochondria–Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury

et al. 2015

ATVB

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Objective-We explored the role of endoplasmic reticulum (ER)-mitochondria Ca 2+ cross talk involving voltage-dependent anion channel-1 (VDAC1)/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex and mitofusin 2 in endothelial cells during hypoxia/reoxygenation (H/R), and investigated the protective effects of acetylcholine. Approach and Results-Acetylcholine treatment during reoxygenation prevented intracellular and mitochondrial Ca 2+ increases and alleviated ER Ca 2+ depletion during H/R in human umbilical vein endothelial cells. Consequently, acetylcholine enhanced mitochondrial membrane potential and inhibited proapoptotic cascades, thereby reducing cell death and preserving endothelial ultrastructure. This effect was likely mediated by the type-3 muscarinic acetylcholine receptor and the phosphatidylinositol 3-kinase/Akt pathway. In addition, interactions among members of the VDAC1/ glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex were increased after H/R and were associated with mitochondrial Ca 2+ overload and cell death. Inhibition of the partner of the Ca 2+ channeling complex (VDAC1 siRNA) or a reduction in ER-mitochondria tethering (mitofusin 2 siRNA) prevented the increased protein interaction within the complex and reduced mitochondrial Ca 2+ accumulation and subsequent endothelial cell death after H/R. Intriguingly, acetylcholine could modulate ER-mitochondria Ca 2+ cross talk by inhibiting the VDAC1/glucoseregulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex and mitofusin 2 expression. Phosphatidylinositol 3-kinase siRNA diminished acetylcholine-mediated inhibition of mitochondrial Ca 2+ overload and VDAC1/glucoseregulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex formation induced by H/R. Conclusions-Our data suggest that ER-mitochondria interplay plays an important role in reperfusion injury in the endothelium and may be a novel molecular target for endothelial protection. Acetylcholine attenuates both intracellular and mitochondrial Ca 2+ overload and protects endothelial cells from H/R injury, presumably by disrupting the ER-mitochondria interaction.

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Section: Discussionmentioning

confidence: 79%

Reduction of Mitochondria–Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury

et al. 2015

ATVB

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“…The results of the present study demonstrated that VS was capable of decreasing myocardial enzyme expression levels and cardiomyocyte apoptosis, which is an important mechanism of cell death. Furthermore, previous studies (16)(17)(18) have demonstrated that VS or the neurotransmitter ACh may exert cardioprotective effects through the regulation of mitochondrial biogenesis and function. The prolonged opening of the mitochondrial permeability transition pore induces cell death through the rapid depletion of ATP and activation of death messengers, such as caspases, which have a key role in apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulation attenuates myocardial ischemia/reperfusion injury by inhibiting the expression of interleukin-17A

Zhang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Interleukin (IL)-17A has an important role in myocardial ischemia/reperfusion (I/R) injury, and vagal stimulation (VS) has been demonstrated to exert cardioprotective effects. The present study aimed to investigate the effects of VS on a rat model of myocardial I/R injury, and detected an association between VS and IL-17A. Anesthetized rats underwent VS (2 msec; 10 Hz) or were treated with anti-IL-17A neutralized monoclonal antibodies (mAbs) (200 µg; iv), and subjected to ischemia for 30 min prior to 4 h reperfusion. The following parameters were measured: Infarct size; lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) and caspase-3 activity levels; tumor necrosis factor (TNF)-α and IL-6 expression levels; and the percentage of terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling (TUNEL) positive cells. High mobility group box 1 protein (HMGB1) and IL-17A expression levels were assessed by immunoblotting. Following 4 h reperfusion, VS was able to significantly decrease the infarct size and the activity levels of LDH and CK (P<0.05). Furthermore, VS administration significantly suppressed the increased MDA and decreased SOD activity levels, and significantly reduced caspase-3 activity and the percentage of TUNEL-positive cells (P<0.05). Treatment with anti-IL-17A mAbs demonstrated the same effects as VS. Furthermore, VS was able to significantly inhibit the increased expression levels of TNF-α, IL-6, HMGB1 and IL-17A induced by I/R (P<0.05). The results of the present study suggested that VS may attenuate myocardial I/R injury by reducing the expression of inflammatory cytokines, oxidative stress and the apoptosis of cardiomyocytes. Furthermore, VS may induce cardioprotective effects, which may be associated with the inhibition of IL-17A expression.

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“…In conscious animal with healed myocardial infarction, direct vagal stimulation also effectively prevents ventricular arrhythmias including ventricular fibrillation [13,44]. Multiple mechanisms are shown to involve in the anti-arrhythmic effect of VNS, such as bradycardiac effect [42], anti-adrenergic effects [4], prevention of the loss of phosphorylated connexin 43 proteins [45], and inhibition of the opening of the mitochondrial permeability transition pore [46]. Although the cardiac protective effect of VNS is mainly mediated by muscarinic receptor, recent study indicated that the vagal antifibrillatory action can be mediated by neuronal nitric oxide released by intracardiac neurons or nerve fibers [47], which reduces the maximal slope of the ventricular action potential restitution curves [48].…”

Section: Es-pns and Vasmentioning

confidence: 99%

Autonomic Modulation by Electrical Stimulation of the Parasympathetic Nervous System: An Emerging Intervention for Cardiovascular Diseases

et al. 2016

Cardiovascular Therapeutics

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SUMMARYThe cardiac autonomic nervous system has been known to play an important role in the development and progression of cardiovascular diseases. Autonomic modulation by electrical stimulation of the parasympathetic nervous system, which increases the parasympathetic activity and suppresses the sympathetic activity, is emerging as a therapeutic strategy for the treatment of cardiovascular diseases. Here, we review the recent literature on autonomic modulation by electrical stimulation of the parasympathetic nervous system, including vagus nerve stimulation, transcutaneous auricular vagal stimulation, spinal cord stimulation, and ganglionated plexi stimulation, in the treatment of heart failure, atrial fibrillation, and ventricular arrhythmias.The cardiac autonomic nervous system, consisting of the sympathetic and the parasympathetic components, has been shown to play an important role in many cardiovascular diseases, such as heart failure, hypertension, atrial fibrillation, and ventricular arrhythmias [1][2][3][4]. An increased sympathetic nerve activity and a reduction of vagal cardiac tone are shown to be pathogenic in most of these conditions. In light of the autonomic imbalance involved in the development and progression of cardiovascular diseases, therapeutic interventions are focused on the inhibition of the sympathetic activation such as the use of b-receptor blockers, cardiac sympathetic denervation, and renal sympathetic denervation, and the increase of the parasympathetic activity such as vagus nerve stimulation. During the last decades, dysregulation of the autonomic nervous system in cardiovascular diseases has received considerable attention and interventions aiming at autonomic rebalance are emerging as new therapeutic options for the management of cardiovascular diseases. Autonomic modulation by electrical stimulation of the autonomic nervous system has been used clinically in patients with intractable angina pectoris [5][6][7], epilepsy [8], and depression [9,10]. Here, we review the experimental studies and clinical trials that are focused on autonomic modulation by electrical stimulation of the parasympathetic nervous system (ES-PNS), including vagus nerve stimulation (VNS), transcutaneous auricular vagal stimulation (tragus stimulation, TS), spinal cord stimulation (SCS), and ganglionated plexi stimulation (GPS), in the treatment of heart failure (HF), atrial fibrillation (AF), and ventricular arrhythmias (VAs). ES-PNS and HFSympathetic activation and parasympathetic withdrawal are the characteristics of autonomic imbalance in HF [2,11,12] [19], the ANTHEM-HF Trial, in which either left or right VNS was performed using an open-loop stimulation system. However, another randomized controlled trial, the NECTAR-HF trial [20], in which 96 symptomatic HF patients were randomized in a 2:1 ratio to receive VNS or control for a 6-month period, showed that VNS failed to significantly improve the primary and secondary endpoint measures of cardiac remodeling and functional capacity, even though quality-...

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Vagal nerve stimulation prevents reperfusion injury through inhibition of opening of mitochondrial permeability transition pore independent of the bradycardiac effect

Abstract: Vagal stimulation would be a potential adjuvant therapy for the rescue of ischemic myocardium from reperfusion injury, and the protective effects are independent of its bradycardiac effects.

Cited by 122 publications

References 28 publications

Reduction of Mitochondria–Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury

Reduction of Mitochondria–Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury

Vagus nerve stimulation attenuates myocardial ischemia/reperfusion injury by inhibiting the expression of interleukin-17A

Autonomic Modulation by Electrical Stimulation of the Parasympathetic Nervous System: An Emerging Intervention for Cardiovascular Diseases

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