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Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury

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A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Microenvironment".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 25934

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Dr. Walter Balduini

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Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
Interests: cerebral hypoxia/ischemia; neuronal death and regeneration; neuroprotection
Special Issues, Collections and Topics in MDPI journals

Dr. Kelly L. Drew

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Center for Transformative Research in Metabolism, Institute of Arctic Biology and Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, AK, USA
Interests: targeted temperature management; synthetic torpor; cardiac arrest; cerebral ischemia/reperfusion injury; hibernation; torpor

Dr. Georgios Tsivgoulis

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Second Department of Neurology, “Atttikon” University Hospital, National and Kapodistrian University of Athens, Athens, Greece
Interests: neurology; stroke; epidemiology; evidence-based medicine; rare neurological diseases

Special Issue Information

Dear Colleagues,

Ischemia-reperfusion injury means that reperfusion after ischemia for a period of time not only fails to restore the function of tissues and organs, but aggravates the dysfunction and structural damage to tissues and organs. This kind of tissue damage is aggravated after restoring blood flow on the basis of ischemia, and even irreversible damage occurs. The incidence of ischemia-reperfusion injury is increasing year by year, and it is common in clinical practice, such as ischemia-reperfusion injury of various important organs such as the heart, brain, liver, etc., multi-organ reperfusion injury caused by trauma or abnormal blood system, and Systemic tissue ischemia-reperfusion injury due to cardiac dysfunction.

This Special Issue of Cells is devoted to summarizing current knowledge and discussing recent advances in both diagnosis and treatment of Ischemia and Reperfusion Injury. We seek the submission of articles and review papers on topics including, but not limited to, Ischemia and Reperfusion Injury diagnosis and treatment.

We look forward to your contributions.

Dr. Walter Balduini
Dr. Kelly L. Drew
Dr. Georgios Tsivgoulis
Guest Editors

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Dr. Kelly L. Drew
Dr. Walter Balduini
Dr. Georgios Tsivgoulis
Guest Editors

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Keywords

targeted temperature management
synthetic torpor
cardiac arrest
cerebral ischemia/reperfusion injury
hibernation
torpor

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19 pages, 4844 KiB

Open AccessArticle

MicroRNA-30d-5p—A Potential New Therapeutic Target for Prevention of Ischemic Cardiomyopathy after Myocardial Infarction

by Elke Boxhammer, Vera Paar, Bernhard Wernly, Attila Kiss, Moritz Mirna, Achim Aigner, Eylem Acar, Simon Watzinger, Bruno K. Podesser, Roland Zauner, Verena Wally, Michael Ablinger, Matthias Hackl, Uta C. Hoppe and Michael Lichtenauer

Cells 2023, 12(19), 2369; https://doi.org/10.3390/cells12192369 - 27 Sep 2023

Cited by 2 | Viewed by 1707

Abstract

(1) Background and Objective: MicroRNAs (miRs) are biomarkers for assessing the extent of cardiac remodeling after myocardial infarction (MI) and important predictors of clinical outcome in heart failure. Overexpression of miR-30d-5p appears to have a cardioprotective effect. The aim of the present study was to demonstrate whether miR-30d-5p could be used as a potential therapeutic target to improve post-MI adverse remodeling. (2) Methods and Results: MiR profiling was performed by next-generation sequencing to assess different expression patterns in ischemic vs. healthy myocardium in a rat model of MI. MiR-30d-5p was significantly downregulated (p < 0.001) in ischemic myocardium and was selected as a promising target. A mimic of miR-30d-5p was administered in the treatment group, whereas the control group received non-functional, scrambled siRNA. To measure the effect of miR-30d-5p on infarct area size of the left ventricle, the rats were randomized and treated with miR-30d-5p or scrambled siRNA. Histological planimetry was performed 72 h and 6 weeks after induction of MI. Infarct area was significantly reduced at 72 h and at 6 weeks by using miR-30d-5p (72 h: 22.89 ± 7.66% vs. 35.96 ± 9.27%, p = 0.0136; 6 weeks: 6.93 ± 4.58% vs. 12.48 ± 7.09%, p = 0.0172). To gain insight into infarct healing, scratch assays were used to obtain information on cell migration in human umbilical vein endothelial cells (HUVECs). Gap closure was significantly faster in the mimic-treated cells 20 h post-scratching (12.4% more than the scrambled control after 20 h; p = 0.013). To analyze the anti-apoptotic quality of miR-30d-5p, the ratio between phosphorylated p53 and total p53 was evaluated in human cardiomyocytes using ELISA. Under the influence of the miR-30d-5p mimic, cardiomyocytes demonstrated a decreased pp53/total p53 ratio (0.66 ± 0.08 vs. 0.81 ± 0.17), showing a distinct tendency (p = 0.055) to decrease the apoptosis rate compared to the control group. (3) Conclusion: Using a mimic of miR-30d-5p underlines the cardioprotective effect of miR-30d-5p in MI and could reduce the risk for development of ischemic cardiomyopathy. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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15 pages, 2719 KiB

Open AccessArticle

Mesenchymal Stem Cells Delivered Locally to Ischemia-Reperfused Kidneys via Injectable Hyaluronic Acid Hydrogels Decrease Extracellular Matrix Remodeling 1 Month after Injury in Male Mice

by Daniel S. Han, Christopher Erickson, Kirk C. Hansen, Lara Kirkbride-Romeo, Zhibin He, Christopher B. Rodell and Danielle E. Soranno

Cells 2023, 12(13), 1771; https://doi.org/10.3390/cells12131771 - 4 Jul 2023

Cited by 6 | Viewed by 1951

Abstract

The translation of stem cell therapies has been hindered by low cell survival and retention rates. Injectable hydrogels enable the site-specific delivery of therapeutic cargo, including cells, to overcome these challenges. We hypothesized that delivery of mesenchymal stem cells (MSC) via shear-thinning and injectable hyaluronic acid (HA) hydrogels would mitigate renal damage following ischemia-reperfusion acute kidney injury. Acute kidney injury (AKI) was induced in mice by bilateral or unilateral ischemia-reperfusion kidney injury. Three days later, mice were treated with MSCs either suspended in media injected intravenously via the tail vein, or injected under the capsule of the left kidney, or MSCs suspended in HA injected under the capsule of the left kidney. Serial measurements of serum and urine biomarkers of renal function and injury, as well as transcutaneous glomerular filtration rate (tGFR) were performed. In vivo optical imaging showed that MSCs localized to both kidneys in a sustained manner after bilateral ischemia and remained within the ipsilateral treated kidney after unilateral ischemic AKI. One month after injury, MSC/HA treatment significantly reduced urinary NGAL compared to controls; it did not significantly reduce markers of fibrosis compared to untreated controls. An analysis of kidney proteomes revealed decreased extracellular matrix remodeling and high overlap with sham proteomes in MSC/HA-treated animals. Hydrogel-assisted MSC delivery shows promise as a therapeutic treatment following acute kidney injury. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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15 pages, 6268 KiB

Open AccessArticle

Amazonia Phytotherapy Reduces Ischemia and Reperfusion Injury in the Kidneys

by Brenner Kássio Ferreira de Oliveira, Eloiza de Oliveira Silva, Sara Ventura, Guilherme Henrique Ferreira Vieira, Carla Djamila de Pina Victoria, Rildo Aparecido Volpini and Maria de Fátima Fernandes Vattimo

Cells 2023, 12(13), 1688; https://doi.org/10.3390/cells12131688 - 22 Jun 2023

Viewed by 1495

Abstract

Acute kidney injury (AKI) is defined as a sudden decrease in kidney function. Phytomedicines have shown positive effects in the treatment of AKI worldwide. The aim of this study was to evaluate the effect of Abuta grandifolia on the renal function of rats submitted to AKI. A phytochemical study of the plant was performed through liquid chromatography coupled with mass spectrometry (CL-EM) and DPPH and ABTS antioxidant tests. Renal function tests were performed in 20 male adult Wistar rats weighing from 250 to 300 g distributed in the following groups: SHAM (submitted to laparotomy with simulation of renal ischemia); ABUTA (animals that received 400 mg/kg of AG, orally—VO, once a day, for 5 days, with simulation of renal ischemia); I/N (animals submitted to laparotomy for clamping of bilateral renal pedicles for 30 min, followed by reperfusion); ABUTA + I/R (animals that received AG—400 mg/kg, 1× per day, VO, for 5 days, submitted to renal ischemia after treatment with herbal medicine). The results suggest that the consumption of Abuta grandifolia promoted renoprotection, preventing the reduction of renal function induced by ischemia, oxidizing activity, and deleterious effects on the renal tissue, confirmed by the decrease of oxidative metabolites and increase of antioxidants in the animals’ organisms. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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17 pages, 2725 KiB

Open AccessArticle

Immune Cells Are Differentially Modulated in the Heart and the Kidney during the Development of Cardiorenal Syndrome 3

by Imara Caridad Stable Vernier, Raquel Silva Neres-Santos, Vinicius Andrade-Oliveira and Marcela Sorelli Carneiro-Ramos

Cells 2023, 12(4), 605; https://doi.org/10.3390/cells12040605 - 13 Feb 2023

Cited by 2 | Viewed by 2213

Abstract

Cardiorenal syndrome type 3 (CRS 3) occurs when there is an acute kidney injury (AKI) leading to the development of an acute cardiac injury. The immune system is involved in modulating the severity of kidney injury, and the role of immune system cells in the development of CRS 3 is not well established. The present work aims to characterize the macrophage and T and B lymphocyte populations in kidney and heart tissue after AKI induced by renal I/R. Thus, C57BL/6 mice were subjected to a renal I/R protocol by occlusion of the left renal pedicle (unilateral) for 60 min, followed by reperfusion for 3, 8 and 15 days. The immune cell populations of interest were identified using flow cytometry, and RT-qPCR was used to evaluate gene expression. As a result, a significant increase in TCD4+, TCD8+ lymphocytes and M1 macrophages to the renal tissue was observed, while B cells in the heart decreased. A renal tissue repair response characterized by Foxp3 activation predominated. However, a more inflammatory profile was shown in the heart tissue influenced by IL-17RA and IL-1β. In conclusion, the AKI generated by renal I/R was able to activate and recruit T and B lymphocytes and macrophages, as well as pro-inflammatory mediators to renal and cardiac tissue, showing the role of the immune system as a bridge between both organs in the context of CRS 3. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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12 pages, 2286 KiB

Open AccessArticle

Lyophilized Extracellular Vesicles from Adipose-Derived Stem Cells Increase Muscle Reperfusion but Degrade Muscle Structural Proteins in a Mouse Model of Hindlimb Ischemia-Reperfusion Injury

by Bharati Mendhe, Mohammad B. Khan, Damon Dunwody, Khairat Bahgat Youssef El Baradie, Kathryn Smith, Wenbo Zhi, Ashok Sharma, Tae Jin Lee and Mark W. Hamrick

Cells 2023, 12(4), 557; https://doi.org/10.3390/cells12040557 - 9 Feb 2023

Cited by 4 | Viewed by 2491

Abstract

Ischemia-reperfusion (I/R) injury is a complication impacting multiple organs and tissues in clinical conditions ranging from peripheral arterial disease to musculoskeletal trauma and myocardial infarction. Stem cell-derived extracellular vesicles (EVs) may represent one therapeutic resource for preventing the tissue damage associated with I/R injury. Here we tested the hypothesis that lyophilized extracellular vesicles derived from adipose stem cells could serve as an “off-the-shelf” treatment modality for I/R injury in a mouse hindlimb ischemia model. Ischemia was induced for 90 min using a rubber band tourniquet and extracellular vesicles (0, 50, or 100 µg) administered via tail vein injection immediately prior to reperfusion. Perfusion was measured prior to, during, and after ischemia using laser Doppler imaging. Serum and tissue were collected 24 h after reperfusion. Mass spectrometry (MS)-based proteomics was used to characterize the EV cargo and proteins from the ischemic and non-ischemic hindlimb. Inflammatory cytokines were measured in muscle and serum using a multiplex array. Results indicate that EVs significantly increase reperfusion and significantly increase expression of the anti-inflammatory factor annexin a1 in skeletal muscle; however, the increased reperfusion was also associated with a marked decrease in muscle structural proteins such as dystrophin, plectin, and obscurin. Circulating inflammatory cytokines TNF-alpha and IL-6 were increased with EV treatment, and serum TNF-alpha showed a significant, positive correlation with reperfusion level. These findings suggest that, while EVs may enhance reperfusion, the increased reperfusion can negatively impact muscle tissue and possibly remote organs. Alternative approaches, such as targeting mitochondrial permeability, may be more effective at mitigating I/R injury. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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19 pages, 4464 KiB

Open AccessArticle

Therapeutic Hypothermia after Cardiac Arrest Attenuates Hindlimb Paralysis and Damage of Spinal Motor Neurons and Astrocytes through Modulating Nrf2/HO-1 Signaling Pathway in Rats

by Ji Hyeon Ahn, Tae-Kyeong Lee, Dae Won Kim, Myoung Cheol Shin, Jun Hwi Cho, Jae-Chul Lee, Hyun-Jin Tae, Joon Ha Park, Seongkweon Hong, Choong-Hyun Lee, Moo-Ho Won and Yang Hee Kim

Cells 2023, 12(3), 414; https://doi.org/10.3390/cells12030414 - 26 Jan 2023

Cited by 2 | Viewed by 2079

Abstract

Cardiac arrest (CA) and return of spontaneous circulation (ROSC), a global ischemia and reperfusion event, lead to neuronal damage and/or death in the spinal cord as well as the brain. Hypothermic therapy is reported to protect neurons from damage and improve hindlimb paralysis after resuscitation in a rat model of CA induced by asphyxia. In this study, we investigated roles of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the lumbar spinal cord protected by therapeutic hypothermia in a rat model of asphyxial CA. Male Sprague-Dawley rats were subjected to seven minutes of asphyxial CA (induced by injection of 2 mg/kg vecuronium bromide) and hypothermia (four hours of cooling, 33 ± 0.5 °C). Survival rate, hindlimb motor function, histopathology, western blotting, and immunohistochemistry were examined at 12, 24, and 48 h after CA/ROSC. The rats of the CA/ROSC and hypothermia-treated groups had an increased survival rate and showed an attenuated hindlimb paralysis and a mild damage/death of motor neurons located in the anterior horn of the lumbar spinal cord compared with those of the CA/ROSC and normothermia-treated groups. In the CA/ROSC and hypothermia-treated groups, expressions of cytoplasmic and nuclear Nrf2 and HO-1 were significantly higher in the anterior horn compared with those of the CA/ROSC and normothermia-treated groups, showing that cytoplasmic and nuclear Nrf2 was expressed in both motor neurons and astrocytes. Moreover, in the CA/ROSC and hypothermia-treated group, interleukin-1β (IL-1β, a pro-inflammatory cytokine) expressed in the motor neurons was significantly reduced, and astrocyte damage was apparently attenuated compared with those found in the CA/ROSC and normothermia group. Taken together, our results indicate that hypothermic therapy after CA/ROSC attenuates CA-induced hindlimb paralysis by protecting motor neurons in the lumbar spinal cord via activating the Nrf2/HO-1 signaling pathway and attenuating pro-inflammation and astrocyte damage (reactive astrogliosis). Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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6 pages, 898 KiB

Open AccessCommunication

Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion

by Axel Haarmann, Christoph Vollmuth, Alexander M. Kollikowski, Peter U. Heuschmann, Mirko Pham, Guido Stoll, Hermann Neugebauer and Michael K. Schuhmann

Cells 2023, 12(2), 288; https://doi.org/10.3390/cells12020288 - 11 Jan 2023

Cited by 5 | Viewed by 1460

Abstract

Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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15 pages, 1987 KiB

Open AccessFeature PaperArticle

Azilsartan Modulates HMGB1/NF-κB/p38/ERK1/2/JNK and Apoptosis Pathways during Renal Ischemia Reperfusion Injury

by Rania Alaaeldin, Sally M. Bakkar, Reham H. Mohyeldin, Fares E. M. Ali, Nehad M. Reda Abdel-Maqsoud and Moustafa Fathy

Cells 2023, 12(1), 185; https://doi.org/10.3390/cells12010185 - 2 Jan 2023

Cited by 15 | Viewed by 2847

Abstract

Renal ischemia/reperfusion (IR) injury is characterized by an unexpected impairment of blood flow to the kidney. Azilsartan is an angiotensin receptor blocker that is approved for the management of hypertension. The present study aimed to investigate, on molecular basics, the nephroprotective activity of azilsartan on renal IR injury in rats. Rats were assigned into four groups: (1) Sham group, (2) Azilsartan group, (3) IR group, and (4) IR/Azilsartan-treated group. Histological examination and renal function were evaluated. Levels of KIM-1, HMGB1, caspase 3, GPX, SOD, NF-κB, and p53 proteins were investigated using ELISA. mRNA levels of IL-1β, IL6, IL10, TNF-α, NF-κB, p53, and bax were assessed by qRT-PCR. Expression of p38, JNK, and ERK1/2 proteins was investigated by Western blotting. IR injury resulted in tissue damage, elevation of creatinine, BUN, KIM-1, HMGB1, caspase 3, NF-κB, and p53 levels, decreasing GPX and SOD activities, and up-regulation of NF-κB, IL-1β, IL6, TNF-α, p53, and bax genes. Furthermore, it up-regulated the expression of phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Interestingly, treatment of the injured rats with azilsartan significantly alleviated IR injury-induced histopathological and biochemical changes. It reduced the creatinine, BUN, KIM-1, HMGB1, caspase-3, NF-κB, and p53 levels, elevated GPX and SOD activities, down-regulated the expression of NF-κB, IL-1β, IL6, TNF-α, p53, and bax genes, and up-regulated IL10 gene expression. Furthermore, it decreased the phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Azilsartan exhibited nephroprotective activity in IR-injured rats via its antioxidant effect, suppression of inflammation, attenuation of apoptosis, and inhibition of HMGB1/NF-κB/p38/ERK1/2/JNK signaling pathway. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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20 pages, 2597 KiB

Open AccessArticle

Melatonin Attenuates Ischemic-like Cell Injury by Promoting Autophagosome Maturation via the Sirt1/FoxO1/Rab7 Axis in Hippocampal HT22 Cells and in Organotypic Cultures

by Francesca Luchetti, Maria G. Nasoni, Sabrina Burattini, Atefeh Mohammadi, Marica Pagliarini, Barbara Canonico, Patrizia Ambrogini, Walter Balduini, Russel J. Reiter and Silvia Carloni

Cells 2022, 11(22), 3701; https://doi.org/10.3390/cells11223701 - 21 Nov 2022

Cited by 6 | Viewed by 2433

Abstract

Dysfunctional autophagy is linked to neuronal damage in ischemia/reperfusion injury. The Ras-related protein 7 (Rab7), a member of the Rab family of small GTPases, appears crucial for the progression of the autophagic flux, and its activity is strictly interconnected with the histone deacetylase Silent information regulator 1 (Sirt1) and transcription factor Forkhead box class O1 (FoxO1). The present study assessed the neuroprotective role of melatonin in the modulation of the Sirt1/FoxO1/Rab7 axis in HT22 cells and organotypic hippocampal cultures exposed to oxygen-glucose deprivation followed by reoxygenation (OGD/R). The results showed that melatonin re-established physiological levels of autophagy and reduced propidium iodide-positive cells, speeding up autophagosome (AP) maturation and increasing lysosomal activity. Our study revealed that melatonin modulates autophagic pathways, increasing the expression of both Rab7 and FoxO1 and restoring the Sirt1 expression affected by OGD/R. In addition, the Sirt1 inhibitor EX-527 significantly reduced Rab7, Sirt1, and FoxO1 expression, as well as autolysosomes formation, and blocked the neuroprotective effect of melatonin. Overall, our findings provide, for the first time, new insights into the neuroprotective role of melatonin against ischemic injury through the activation of the Sirt1/FoxO1/Rab7 axis. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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Review

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21 pages, 776 KiB

Open AccessReview

Ischemic Tolerance—A Way to Reduce the Extent of Ischemia–Reperfusion Damage

by Rastislav Burda, Jozef Burda and Radoslav Morochovič

Cells 2023, 12(6), 884; https://doi.org/10.3390/cells12060884 - 13 Mar 2023

Cited by 8 | Viewed by 3335

Abstract

Individual tissues have significantly different resistance to ischemia–reperfusion damage. There is still no adequate treatment for the consequences of ischemia–reperfusion damage. By utilizing ischemic tolerance, it is possible to achieve a significant reduction in the extent of the cell damage due to ischemia–reperfusion injury. Since ischemia–reperfusion damage usually occurs unexpectedly, the use of preconditioning is extremely limited. In contrast, postconditioning has wider possibilities for use in practice. In both cases, the activation of ischemic tolerance can also be achieved by the application of sublethal stress on a remote organ. Despite very encouraging and successful results in animal experiments, the clinical results have been disappointing so far. To avoid the factors that prevent the activation of ischemic tolerance, the solution has been to use blood plasma containing tolerance effectors. This plasma is taken from healthy donors in which, after exposure to two sublethal stresses within 48 h, effectors of ischemic tolerance occur in the plasma. Application of this activated plasma to recipient animals after the end of lethal ischemia prevents cell death and significantly reduces the consequences of ischemia–reperfusion damage. Until there is a clear chemical identification of the end products of ischemic tolerance, the simplest way of enhancing ischemic tolerance will be the preparation of activated plasma from young healthy donors with the possibility of its immediate use in recipients during the initial treatment. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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24 pages, 1499 KiB

Open AccessReview

Ferroptosis—A New Dawn in the Treatment of Organ Ischemia–Reperfusion Injury

by Linxiang Zhou, Shangting Han, Jiayu Guo, Tao Qiu, Jiangqiao Zhou and Lei Shen

Cells 2022, 11(22), 3653; https://doi.org/10.3390/cells11223653 - 17 Nov 2022

Cited by 24 | Viewed by 3059

Abstract

Ischemia–reperfusion (I/R) is a common pathological phenomenon that occurs in numerous organs and diseases. It generally results from secondary damage caused by the recovery of blood flow and reoxygenation, followed by ischemia of organ tissues, which is often accompanied by severe cellular damage and death. Currently, effective treatments for I/R injury (IRI) are limited. Ferroptosis, a new type of regulated cell death (RCD), is characterized by iron overload and iron-dependent lipid peroxidation. Mounting evidence has indicated a close relationship between ferroptosis and IRI. Ferroptosis plays a significantly detrimental role in the progression of IRI, and targeting ferroptosis may be a promising approach for treatment of IRI. Considering the substantial progress made in the study of ferroptosis in IRI, in this review, we summarize the pathological mechanisms and therapeutic targets of ferroptosis in IRI. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Organ Damage in Ischemia and Reperfusion Injury)

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