Molecular mechanisms of autophagy in cardiac ischemia/reperfusion injury (Review)

Nuclear factor erythroid-2 related factor 2 (Nrf2) is a transcription factor that controls cellular defense responses against toxic and oxidative stress by modulating the expression of genes involved in antioxidant response and drug detoxification. In addition to maintaining redox homeostasis, Nrf2 is also involved in various cellular processes including metabolism and inflammation. Nrf2 activity is tightly regulated at the transcriptional, post-transcriptional and post-translational levels, which allows cells to quickly respond to pathological stress. In the present review, we describe the molecular mechanisms underlying the transcriptional regulation of Nrf2. We also focus on the impact of Nrf2 in cardiac ischemia–reperfusion injury, a condition that stimulates the overproduction of reactive oxygen species. Finally, we analyze the protective effect of several natural and synthetic compounds that induce Nrf2 activation and protect against ischemia–reperfusion injury in the heart and other organs, and their potential clinical application.

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The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

Journal of the American Society of Nephrology ◽

10.1681/asn.2019050534 ◽

2020 ◽

Vol 31 (4) ◽

pp. 716-730 ◽

Cited By ~ 1

Author(s):

Marc Johnsen ◽

Torsten Kubacki ◽

Assa Yeroslaviz ◽

Martin Richard Späth ◽

Jannis Mörsdorf ◽

...

Keyword(s):

Gene Expression ◽

Reperfusion Injury ◽

Caloric Restriction ◽

Molecular Mechanisms ◽

Target Genes ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Hypoxic Preconditioning ◽

Preventive Strategies ◽

Gene Expression Signatures

BackgroundAlthough AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance.MethodsTo identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury.ResultsThe gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI.ConclusionsThis comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

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406-1 Hypoxia regulatable Aav-2 vector protects against cardiac ischemia/reperfusion injury

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(04)92260-7 ◽

2004 ◽

Vol 43 (5) ◽

pp. A533

Author(s):

Alok S Pachori ◽

Luis G Melo ◽

Lunan Zhang ◽

Richard E Pratt ◽

Victor J Dzau

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cardiac Ischemia

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INHIBITION OF APOPTOSIS AND FERROPTOSIS EXERTS HIGHER EFFICACY IN REDUCING CARDIAC ISCHEMIA/REPERFUSION INJURY THAN NECROPTOSIS INHIBITOR IN RATS

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(21)01489-3 ◽

2021 ◽

Vol 77 (18) ◽

pp. 130

Author(s):

Ying Luo ◽

Suchan Liao ◽

Jun Wu ◽

Busarin Arunsak ◽

Thidarat Jaiwongkam ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cardiac Ischemia

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Mitochondria-associated membrane-modulated Ca2+ transfer: A potential treatment target in cardiac ischemia reperfusion injury and heart failure

Life Sciences ◽

10.1016/j.lfs.2021.119511 ◽

2021 ◽

pp. 119511

Author(s):

Yingchao Gong ◽

Jun Lin ◽

Zetao Ma ◽

Mei Yu ◽

Meihui Wang ◽

...

Keyword(s):

Heart Failure ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cardiac Ischemia ◽

Potential Treatment ◽

Treatment Target

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Nanoparticle-Mediated Dual Delivery of an Antioxidant and a Peptide against the L-Type Ca2+ Channel Enables Simultaneous Reduction of Cardiac Ischemia-Reperfusion Injury

ACS Nano ◽

10.1021/nn5061404 ◽

2014 ◽

Vol 9 (1) ◽

pp. 279-289 ◽

Cited By ~ 23

Author(s):

Naviin Hardy ◽

Helena M. Viola ◽

Victoria P. A. Johnstone ◽

Tristan D. Clemons ◽

Henrietta Cserne Szappanos ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cardiac Ischemia ◽

Simultaneous Reduction

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Hemorheological and Microcirculatory Factors in Liver Ischemia-Reperfusion Injury—An Update on Pathophysiology, Molecular Mechanisms and Protective Strategies

International Journal of Molecular Sciences ◽

10.3390/ijms22041864 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1864

Author(s):

Norbert Nemeth ◽

Katalin Peto ◽

Zsuzsanna Magyar ◽

Zoltan Klarik ◽

Gabor Varga ◽

...

Keyword(s):

Reperfusion Injury ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Tissue Perfusion ◽

Comprehensive Overview ◽

Hepatic Ischemia ◽

Continuous Increase ◽

Ischemic Conditioning ◽

Stress Dependent

Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular–pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches.

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