Cardiomyocytes-specific deletion of monoamine oxidase B reduces irreversible myocardial ischemia/reperfusion injury

Heger, Jacqueline; Hirschhäuser, Christine; Bornbaum, Julia; Sydykov, Akylbek; Dempfle, Astrid; Schneider, André; Braun, Thomas; Schlüter, Klaus‐Dieter; Schulz, Rainer

doi:10.1016/j.freeradbiomed.2021.01.020

Cited by 24 publications

(25 citation statements)

References 44 publications

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“…Apoptosis-, ROS- and inflammation-induced myocardial loss represents the most pivotal agents in MIRI 2 , 7 , 9 , 10 , 14 , 34 – 36 . In this way, acute impairment is dramatically induced and allows for subsequent cardiac remodelling post I/R 2 , 3 . In terms of KDM3A in modulating various pathological processes, such as vascular remodeling and ischemic stress 15 , 16 , 19 , we speculated that KDM3A may function as a decisive mediator in the pathogenesis of MIRI.…”

Section: Discussionmentioning

confidence: 99%

“…Timely revascularization, despite the benefits of limiting ischaemic injury and infarct expansion, governs the key endpoints that not only give rise to ischemia/reperfusion (I/R) episodes but also progress to chronic cardiac impairment 1 – 6 . Since achieving success in reperfusion to dampen ischemia, the focus of current experimental and clinical efforts has shifted towards the limitations of myocardial I/R injury (MIRI) to optimize the benefits of revascularization 3 – 5 , 7 – 10 . Although not completely clear, current investigations indicate that MIRI aetiologies consist of diverse cellular events with respect to apoptosis, reactive oxygen species (ROS), and inflammation 11 – 13 .…”

Section: Introductionmentioning

confidence: 99%

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The histone demthylase KDM3A protects the myocardium from ischemia/reperfusion injury via promotion of ETS1 expression

Guo

Zhang

et al. 2022

Commun Biol

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Our prior studies have characterized the participation of histone demethylase KDM3A in diabetic vascular remodeling, while its roles in myocardial ischemia/reperfusion (I/R) injury (MIRI) remain to be illustrated. Here we show that KDM3A was significantly downregulated in rat I/R and cellular hypoxia/reoxygenation (H/R) models. Subsequently, gain- and loss-of-function experiments were performed to investigate the effects of KDM3A in the settings of MIRI. KDM3A knockout exacerbated cardiac dysfunction and cardiomyocytes injury both in vivo and in vitro. The deteriorated mitochondrial apoptosis, reactive oxygen species, and inflammation were simultaneously observed. Conversely, KDM3A overexpression developed the ameliorated alternations in MIRI. Mechanistically, the MIRI-alleviating effects of KDM3A were associated with the enhancement of ETS1 expression. ChIP-PCR affirmed that KDM3A bound to the ETS1 promoter and removed dimethylation of histone H3 lysine 9 (H3K9me2), thus promoting ETS1 transcription. Our findings suggest that KDM3A is available for alleviating multi-etiologies of MIRI through the regulation of ETS1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The histone demthylase KDM3A protects the myocardium from ischemia/reperfusion injury via promotion of ETS1 expression

Guo

Zhang

et al. 2022

Commun Biol

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“…Myocardial I/R injury has had a non-negligible impact on human life and health. Studies have found that in the process of ischemia and reperfusion, the main reason is the explosive production of a large number of oxygen free radicals (16). The oxygen-free radicals generated during I/R injury will react to produce malondialdehyde, which will further affect the cells, so the MDA content can effectively reflect the degree of ischemia-reperfusion injury (17).…”

Section: Changes Of Apoptotic Cells In Myocardial Tissue Of Rats With...mentioning

confidence: 99%

Effect of Cerium Oxide Nanoparticles on Myocardial Cell Apoptosis Induced by Myocardial Ischemia-Reperfusion Injury

Zhao¹,

Yang²,

Wen³

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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This study was to provide a theoretical basis for effective treatment of myocardial ischemia-reperfusion injury (I/R injury) and explore the effect of cerium oxide (CeO2) nanoparticles on myocardial cell apoptosis induced by I/R injury. In this study, 50 healthy male Sprague Dawley (SD) rats were selected and divided into five groups according to the random table method: a sham operation group, an I/R group, a 1 -10 nm CeO2 nanoparticle group (CeO2-1 group), a 10 -25 nm CeO2 nanoparticle group (CeO2-2 group), and a 50 nm CeO2 nanoparticle group (CeO2-3 group). Rats in different groups were injected with phosphate buffer solution (PBS) and CeO2 nanoparticles with different diameters, respectively. The rat models of I/R injury were prepared to explore and analyze the superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, glutathione peroxidase (GSH-Px) activity, and myocardial cell apoptosis of rats with I/R injury by CeO2 nanoparticles. The results showed that the cardiomyocyte necrosis, SOD activity, MDA content, GSH-Px activity, and apoptosis index of the three groups of rats injected with CeO2 nanoparticles were much better than those in the I/R group. The effects on SOD activity, MDA content, GSH-Px activity, and apoptosis index of cardiomyocytes in the CeO2-2 group were significantly better than those in the CeO2-1 and CeO2-3 groups, showing statistically great differences (P< 0.05); and effects on SOD activity, MDA content, and GSH-Px activity of cardiomyocytes in CeO2-1 group were better obviously than those in the CeO2-3 groups, showing statistically observable differences (P< 0.05). In addition, the difference between the CeO2-1 group and CeO2-3 on the apoptosis index of cardiomyocytes was not statistically remarkable (P> 0.05). It can be considered that the CeO2 nanoparticles can effectively alleviate the effects of myocardial I/R injury, showing reliable clinical significance.

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“…Biologically, AMI results from abrupt occlusion of the coronary artery, leading to acute myocardial ischemia and irreversible damage to cardiomyocytes [2]. Therapeutic approaches that are aimed at ameliorating ischemic injuries have been integrated into clinical practice, and timely resumption of blood flow to ischemic myocardium has become a standard therapy [3,4]. However, reperfusion may cause additional damage to the myocardium and compromise the therapeutic benefits, which is termed ischemic and reperfusion (I/R) injury [5].…”

Section: Introductionmentioning

confidence: 99%

KDM3A Attenuates Myocardial Ischemic and Reperfusion Injury by Ameliorating Cardiac Microvascular Endothelial Cell Pyroptosis

Zhang

Liu

Huang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cardiac microvascular endothelial cell ischemia-reperfusion (CMEC I/R) injury occurs in approximately 50% of acute myocardial infarction patients subjected to successful revascularization therapy. This injury leads to cardiac microcirculatory system dysfunctions, which seriously affect cardiac functions and long-term prognostic outcomes. Previously, we elucidated the role of lysine-specific demethylase 3A (KDM3A) in protecting cardiomyocytes from I/R injury; however, its roles in CMEC I/R injuries have yet to be fully established. In this study, hypoxia/reoxygenation (H/R) treatment significantly impaired CMEC functions and induced their pyroptosis, accompanied by KDM3A downregulation. Then, gain- and loss-of-function assays were performed to investigate the roles of KDM3A in CMEC H/R injury in vitro. KDM3A knockout enhanced CMEC malfunctions and accelerated the expressions of pyroptosis-associated proteins, such as NLRP3, cleaved-caspase-1, ASC, IL-1β, GSDMD-N, and IL-18. Conversely, KDM3A overexpression developed ameliorated alternations in CMEC H/R injury. In vivo, KDM3A knockout resulted in the deterioration of cardiac functions and decreased the no-reflow area as well as capillary density. Mechanistically, KDM3A activated the PI3K/Akt signaling pathway and ameliorated I/R-mediated CMEC pyroptosis. In conclusion, KDM3A is a promising treatment target for alleviating CMEC I/R injury.

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Cardiomyocytes-specific deletion of monoamine oxidase B reduces irreversible myocardial ischemia/reperfusion injury

Cited by 24 publications

References 44 publications

The histone demthylase KDM3A protects the myocardium from ischemia/reperfusion injury via promotion of ETS1 expression

The histone demthylase KDM3A protects the myocardium from ischemia/reperfusion injury via promotion of ETS1 expression

Effect of Cerium Oxide Nanoparticles on Myocardial Cell Apoptosis Induced by Myocardial Ischemia-Reperfusion Injury

KDM3A Attenuates Myocardial Ischemic and Reperfusion Injury by Ameliorating Cardiac Microvascular Endothelial Cell Pyroptosis

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