scholarly journals Mitochondrial bioenergetics and cardiolipin alterations in myocardial ischemia-reperfusion injury: implications for pharmacological cardioprotection

2018 ◽  
Vol 315 (5) ◽  
pp. H1341-H1352 ◽  
Author(s):  
Giuseppe Paradies ◽  
Valeria Paradies ◽  
Francesca Maria Ruggiero ◽  
Giuseppe Petrosillo
Keyword(s):  
Myocardial Ischemia ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Morphology ◽  
Myocardial Ischemia Reperfusion

Mitochondrial dysfunction plays a central role in myocardial ischemia-reperfusion (I/R) injury. Increased reactive oxygen species production, impaired electron transport chain activity, aberrant mitochondrial dynamics, Ca2+ overload, and opening of the mitochondrial permeability transition pore have been proposed as major contributory factors to mitochondrial dysfunction during myocardial I/R injury. Cardiolipin (CL), a mitochondria-specific phospholipid, plays a pivotal role in multiple mitochondrial bioenergetic processes, including respiration and energy conversion, in mitochondrial morphology and dynamics as well as in several steps of the apoptotic process. Changes in CL levels, species composition, and degree of oxidation may have deleterious consequences for mitochondrial function with important implications in a variety of pathophysiological conditions, including myocardial I/R injury. In this review, we focus on the role played by CL alterations in mitochondrial dysfunction in myocardial I/R injury. Pharmacological strategies to prevent myocardial injury during I/R targeting mitochondrial CL are also examined.

scholarly journals Mitochondria “THE” target of myocardial conditioning

2018 ◽  
Vol 315 (5) ◽  
pp. H1215-H1231 ◽  
Author(s):  
Kerstin Boengler ◽  
Günter Lochnit ◽  
Rainer Schulz
Keyword(s):  
Reperfusion Injury ◽  
Mitochondrial Function ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Several interventions, such as ischemic preconditioning, remote pre/perconditioning, or postconditioning, are known to decrease lethal myocardial ischemia-reperfusion injury. While several signal transduction pathways become activated by such maneuvers, they all have a common end point, namely, the mitochondria. These organelles represent an essential target of the cardioprotective strategies, and the preservation of mitochondrial function is central for the reduction of ischemia-reperfusion injury. In the present review, we address the role of mitochondria in the different conditioning strategies; in particular, we focus on alterations of mitochondrial function in terms of energy production, formation of reactive oxygen species, opening of the mitochondrial permeability transition pore, and mitochondrial dynamics induced by ischemia-reperfusion.

scholarly journals Does p53 Inhibition Suppress Myocardial Ischemia–Reperfusion Injury?

2018 ◽  
Vol 23 (4) ◽  
pp. 350-357 ◽  
Author(s):  
Toshiyuki Yano ◽  
Koki Abe ◽  
Masaya Tanno ◽  
Takayuki Miki ◽  
Atsushi Kuno ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Late Phase ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Rate Pressure Product ◽  
Myocardial Ischemia Reperfusion

p53 is well known as a regulator of apoptosis and autophagy. In addition, a recent study showed that p53 is a modulator of the opening of the mitochondrial permeability transition pore (mPTP), a trigger event of necrosis, but the role of p53 in necrosis induced by myocardial ischemia–reperfusion (I/R) remains unclear. The aim of this study was to determine the role of p53 in acute myocardial I/R injury in perfused mouse hearts. In male C57BL6 mice between 12 and 15 weeks of age, 2 types of p53 inhibitors were used to suppress p53 function during I/R: pifithrin-α, an inhibitor of transcriptional functions of p53, and pifithrin-μ, an inhibitor of p53 translocation from the cytosol to mitochondria. Neither infusion of these inhibitors before ischemia nor infusion for the first 30-minute period of reperfusion reduced infarct size after 20-minute ischemia/120-minute reperfusion. Infarct sizes were similar in p53 heterozygous knockout mice (p53+/−) and wild-type mice (WT), but recovery of rate pressure product (RRP) 120 minutes after reperfusion was higher in p53+/− than in WT. The protein expression of p53 in WT was negligible under baseline conditions, during ischemia, and at 10 minutes after the start of reperfusion, but it became detectable at 120 minutes after reperfusion. In conclusion, upregulation of p53 during the late phase of reperfusion plays a significant role in contractile dysfunction after reperfusion, although p53 is not involved in cardiomyocyte necrosis during ischemia or in the early phase of reperfusion.

scholarly journals The Effect of Ginsenoside RB1, Diazoxide, and 5-Hydroxydecanoate on Hypoxia-Reoxygenation Injury of H9C2 Cardiomyocytes

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Heng Zhang ◽  
Xiao Wang ◽  
Yihua Ma ◽  
Yueping Shi
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Ginsenoside Rb1 ◽  
H9c2 Cardiomyocytes ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Hypoxia Reoxygenation

This study was aimed to investigate whether ginsenoside Rb1 (GS-Rb1) from the cardioprotective Chinese medicine ginseng can reduce hypoxia-reoxygenation (HR)-induced damage to cardiomyocytes by protecting the mitochondria. Mitochondria-mediated apoptosis plays a key role during myocardial ischemia-reperfusion injury (MIRI). When MIRI occurs, the continuous opening of the mitochondrial permeability transition pore (mPTP) causes mitochondrial damage and ultimately leads to apoptosis. We treated H9c2 cells, derived from rat embryonic cardiomyoblasts, with GS-Rb1, diazoxide, and 5-hydroxydecanoate (5-HD), using HR to simulate MIRI. We found that GS-Rb1 can reduce mPTP by stabilizing the mitochondrial membrane potential (MMP) and by reducing reactive oxygen species (ROS) during HR. This protects the mitochondria by reducing the release of cytochrome c and the expression of cleaved-caspase-3 in the cytoplasm, ultimately reducing apoptosis. During this process, GS-Rb1 and diazoxide showed similar effects. These findings provide some evidence for a protective effect of GS-Rb1 treatment on MIRI.

scholarly journals Traditional Chinese Medicine Shuang Shen Ning Xin Attenuates Myocardial Ischemia/Reperfusion Injury by Preserving of Mitochondrial Function

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Xueli Li ◽  
Jianxun Liu ◽  
Li Lin ◽  
Yujie Guo ◽  
Chengren Lin ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Mitochondrial Function ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Permeability Transition ◽  
Myocardial Oxidative Stress ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

To investigate the potential cardioprotective effects of Shuang Shen Ning Xin on myocardial ischemia/reperfusion injury. Wistar rats were treated with trimetazidine (10 mg/kg/day, ig), Shuang Shen Ning Xin (22.5, 45 mg/kg/day, ig), or saline for 5 consecutive days. Myocardial ischemia/reperfusion injury was induced by ligation of the left anterior descending coronary artery for 40 min and reperfusion for 120 min on the last day of administration. It is found that Shuang Shen Ning Xin pretreatment markedly decreased infarct size and serum LDH levels, and this observed protection was associated with reduced myocardial oxidative stress and cardiomyocyte apoptosis after myocardial ischemia/reperfusion injury. In addition, further studies on mitochondrial function showed that rats treated with Shuang Shen Ning Xin displayed decreased mitochondrial swelling and cytosolic cytochrome c levels, which were accompanied by a preservation of complex I activities and inhibition of mitochondrial permeability transition. In conclusion, the mitochondrial protective effect of Shuang Shen Ning Xin could be a new mechanism, by which Shuang Shen Ning Xin attenuates myocardial ischemia/reperfusion injury.

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