Novel Aspects of Cardiac Ischemia and Reperfusion Injury Mechanisms

Introduction.The present article, in which a contemporary analysis of the literature on the pathophysiology of ischemic and reperfusion injury (IRI) of the myocardium is presented, focuses on the possible role played by of the calpain system and oxidative stress. Several process development options were proposed, including cytosolic and mitochondrial Ca2+ overload, reactive oxygen stress release, acute inflammatory response and metabolic degradation. The combined effect of all of the above factors produces irreversible ischemic and reperfused damage of cardiomyocytes.Materials and methods.The role of the calpain system in the creation of myocardial IRI was experimentally investigated. It was found that active calpain substrates play a significant role in the processes of cell cycle, apoptosis and differentiation, adversely affecting cardiomyocyte functionality. The calpain system is part of an integrated proteolytic system that is critical to the relationship between the structure and function of the cardiac sarcomere. Uncontrolled activation of calpain is indicated in the pathophysiology of many cardiovascular disorders. As shown by research, inhibitor calpain reduces the size of the zone of infarction following ischemia reperfusion and thus lessens the risk of “stunning” the myocardium. As is known, a consequence of IRI is acute myocardial infarction (AMI), which is a central factor in cardiovascular disease (CVD) and is one of the primary causes of mortality. Understanding the exact pathophysiological mechanisms remains an urgent problem for clinical physicians. To date, the mechanisms of IRI are not fully known, which creates certain difficulties in further treatment and prevention tactics. In addition, myocardial IRI is also an important issue for pathoanatomical service, since sudden coronary death can occur despite timely reperfusion therapy following AMI.Conclusion.The development of strategies for creating conditions that limit the degree of damage to myocardial tissues significantly increases the ability of the heart to withstand ischemic damage.

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Ischemic Preconditioning Preserves Liver Energy Charge and Function on Hepatic Ischemia/Reperfusion Injury in Rats

Archives of Medical Research ◽

10.1016/j.arcmed.2018.11.004 ◽

2018 ◽

Vol 49 (6) ◽

pp. 373-380 ◽

Cited By ~ 1

Author(s):

Sergio Rodríguez-Reynoso ◽

Caridad Leal-Cortés ◽

Eliseo Portilla-de Buen ◽

Selene Paulina López-De la Torre

Keyword(s):

Reperfusion Injury ◽

Ischemic Preconditioning ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Energy Charge ◽

Hepatic Ischemia ◽

Hepatic Ischemia Reperfusion ◽

And Function ◽

Liver Energy Charge

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Fenofibrate Ameliorates Hepatic Ischemia/Reperfusion Injury in Mice: Involvements of Apoptosis, Autophagy, and PPAR-α Activation

PPAR Research ◽

10.1155/2021/6658944 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Jie Zhang ◽

Ping Cheng ◽

Weiqi Dai ◽

Jie Ji ◽

Liwei Wu ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Protective Effects ◽

Hepatocyte Apoptosis ◽

Ischemia And Reperfusion Injury ◽

Hepatic Ischemia ◽

Tissue Samples ◽

Hepatic Ischemia Reperfusion ◽

And Oxidative Stress

Hepatic ischemia and reperfusion injury is characterized by hepatocyte apoptosis, impaired autophagy, and oxidative stress. Fenofibrate, a commonly used antilipidemic drug, has been verified to exert hepatic protective effects in other cells and animal models. The purpose of this study was to identify the function of fenofibrate on mouse hepatic IR injury and discuss the possible mechanisms. A segmental (70%) hepatic warm ischemia model was established in Balb/c mice. Serum and liver tissue samples were collected for detecting pathological changes at 2, 8, and 24 h after reperfusion, while fenofibrate (50 mg/kg, 100 mg/kg) was injected intraperitoneally 1 hour prior to surgery. Compared to the IR group, pretreatment of FF could reduce the inflammatory response and inhibit apoptosis and autophagy. Furthermore, fenofibrate can activate PPAR-α, which is associated with the phosphorylation of AMPK.

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VACCINIA VIRUS COMPLEMENT CONTROL PROTEIN (VCP) IMPROVES KIDNEY STRUCTURE AND FUNCTION FOLLOWING ISCHEMIA/REPERFUSION INJURY IN RATS

Transplantation Journal ◽

10.1097/01.tp.0000331002.33106.57 ◽

2008 ◽

Vol 86 (Supplement) ◽

pp. 601

Author(s):

D Kahn ◽

Y T. Ghebremariam ◽

G Engelbrecht ◽

M Tyler ◽

Z Lotz ◽

...

Keyword(s):

Vaccinia Virus ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Structure And Function ◽

Kidney Structure ◽

Complement Control Protein ◽

And Function ◽

Control Protein

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Diazoxide Protects against Myocardial Ischemia/Reperfusion Injury by Moderating ERS via Regulation of the miR-10a/IRE1 Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4957238 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Lin Zhang ◽

Shuang Cai ◽

Song Cao ◽

Jia Nie ◽

Wenjing Zhou ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Heart Disease ◽

Protective Effect ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Reperfusion Therapy ◽

Potassium Channel Opener ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Nowadays, reperfusion is still the most effective treatment for ischemic heart disease. However, cardiac reperfusion therapy would lead to reperfusion injury, which may have resulted from endoplasmic reticulum stress (ERS) during reperfusion. Diazoxide (DZ) is a highly selective mitochondrial adenosine triphosphate-sensitive potassium channel opener. Its protective effect on I/R injury has been confirmed in many organs such as the heart and brain. However, the mechanism of its protective effect has not been fully elucidated. MicroRNAs (miRNAs) are widely involved in pathologies of heart disease. In this study, we found that miR-10a expression was highly upregulated in the myocardial I/R groups, and DZ treatment significantly reduced the expression of miR-10a. More importantly, we found that DZ treatment can moderate ERS via regulation of the miR-10a/IRE1 pathway in the I/R and H/R models, thereby protecting myocardial H/R injury.

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Beclin 1/Bcl-2 complex-dependent autophagy activity modulates renal susceptibility to ischemia-reperfusion injury and mediates renoprotection by Klotho

AJP Renal Physiology ◽

10.1152/ajprenal.00504.2019 ◽

2020 ◽

Vol 318 (3) ◽

pp. F772-F792 ◽

Cited By ~ 1

Author(s):

Peng Li ◽

Mingjun Shi ◽

Jenny Maique ◽

Joy Shaffer ◽

Shirley Yan ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Genetic Manipulation ◽

Protein Complexes ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Beclin 1 ◽

Klotho Protein ◽

And Function ◽

Autophagy Activity

Klotho- and beclin 1-driven autophagy extends life. We examined the role of beclin 1 in modifying acute kidney injury (AKI) and whether beclin 1 mediates Klotho’s known renoprotective action in AKI. AKI was induced by ischemia-reperfusion injury in mice with different levels of autophagy activity by genetic manipulation: wild-type (WT) mice with normal beclin 1 expression and function, mice with normal beclin 1 levels but high activity through knockin of gain-of-function mutant beclin 1 ( Becn1F121A), mice with low beclin 1 levels and activity caused by heterozygous global deletion of beclin 1 ( Becn1+/−), or mice with extremely low beclin 1 activity from knockin of the mutant constitutively active beclin 1 inhibitor Bcl-2 ( Bcl2AAA). Klotho was increased by transgenic overexpression ( Tg-Kl) or recombinant Klotho protein administration. After ischemia-reperfusion injury, Becn1F121A mice (high autophagy) had milder AKI and Becn1+/− and Bcl2AAA mice (low autophagy) had more severe AKI than WT mice. Tg-Kl mice had milder AKI, but its renoprotection was partially attenuated in Becn1+/− ;Tg-Kl mice and was significantly reduced, although not completely abolished, in Bcl2AAA;Tg-Kl mice. Recombinant Klotho protein conferred more renoprotection from AKI in WT mice than in Becn1+/− or Bcl2AAA mice. Klotho reduced beclin 1/Bcl-2 protein complexes and increased autophagy activity, but this effect was less prominent in mice or cells with Bcl2AAA. Transfected Bcl2AAA or Becn1F123A decreased or increased autophagy activity and rendered cells more susceptible or more resistant to oxidative cytotoxicity, respectively. In conclusion, beclin 1 confers renoprotection by activating autophagy. Klotho protects the kidney partially via disruption of beclin 1/Bcl-2 interactions and enhancement of autophagy activity.

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Past and present course of cardioprotection against ischemia- reperfusion injury

Journal of Applied Physiology ◽

10.1152/japplphysiol.00383.2007 ◽

2007 ◽

Vol 103 (6) ◽

pp. 2129-2136 ◽

Cited By ~ 29

Author(s):

David A. Liem ◽

Henry M. Honda ◽

Jun Zhang ◽

David Woo ◽

Peipei Ping

Keyword(s):

Reperfusion Injury ◽

Mitochondrial Permeability Transition ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Permeability Transition ◽

Reperfusion Therapy ◽

Cardioprotective Effect ◽

Western Society ◽

Cardiovascular Research ◽

Postischemic Reperfusion

Despite tremendous advances in cardiovascular research and clinical therapy, ischemic heart disease remains the leading cause of serious morbidity and mortality in western society and is growing in developing countries. For the past 5 decades, many scientists have studied the pathophysiology of myocardial ischemia-reperfusion (I/R) injury leading to infarction. With the exception of reperfusion therapy, attempts to salvage the myocardium during an acute myocardial infarction showed disappointing results in directly decreasing infarct size. Nevertheless, the phenomena of ischemic preconditioning and ischemic postconditioning show a consistent and robust cardioprotective effect in every used experimental animal model. As a result, many studies have focused on the intracellular protective signaling pathways that are involved in preconditioning and postconditioning. More recently, it has been suggested that components of the reperfusion injury salvage kinases pathway, protein kinase B, and the extracellular signal-regulated kinases can induce cardioprotection against I/R injury when they are activated during the postischemic reperfusion period. In addition, inhibition of mitochondrial permeability transition during postischemic reperfusion also shows a strong cardioprotective effect against I/R injury. The present mini-review highlights a short summary of the historical and present course of research into cardioprotection against myocardial I/R injury.

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