<scp>JMJD5</scp> attenuates oxygen–glucose deprivation and reperfusion‐induced injury in cardiomyocytes through regulation of <scp>HIF‐1α‐BNIP3</scp>

Zhang, Yanan; Pang, Ya-Xiang; Liu, Dawei; Hu, Haijuan; Xie, Ruiqin; Cui, Wei

doi:10.1002/kjm2.12434

Cited by 6 publications

(2 citation statements)

References 29 publications

(34 reference statements)

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“…The present study verified that autophagic flux and mitophagy were inhibited or reduced in both ischaemic and pressure‐overload HF mice, and involved in LC3II, PINK1, PRKN and BECN1 related pathways, although discrepancies existed in the degree and nature of the pathway depending on the HF model, which was generally consistent with the results of the previous studies (Kubli & Gustafsson, 2012; Liu et al., 2012; Morales et al., 2020; Nah et al., 2022; Wang et al., 2018). In addition, HIF1α in the myocardium of mice with both aetiologies of HF was also significantly reduced in the present study, which was consistent with the decreased HIF1α in the study of oxygen–glucose deprivation and reperfusion‐induced injury in cardiomyocytes (Zhang et al., 2022). Combined with the current evidence, it can be concluded that poor mitophagy may serve as a ‘hallmark’ of chronic HF and is closely linked to its pathological development.…”

Section: Discussionsupporting

confidence: 91%

Exercise training improves cardiac function and regulates myocardial mitophagy differently in ischaemic and pressure‐overload heart failure mice

Guo

Chen

Zhao

et al. 2022

Experimental Physiology

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The cardioprotective effects of different aerobic exercises on chronic heart failure with different aetiologies and whether mitophagy is involved remain elusive. In the current research, left anterior descending ligation and transverse aortic constriction surgeries were used to establish mouse models of heart failure, followed by 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). The results showed that for ischaemic heart failure MICT significantly improved ejection fraction (P < 0.05) and fractional shortening (P < 0.05), mitigated left ventricular end-systolic dimension (P < 0.01), decreased brain natriuretic peptide (P < 0.0001) and mitigated fibrosis (P < 0.0001), while HIIT only decreased brain natriuretic peptide (P < 0.0001) and fibrosis (P < 0.0001). For pressure-overload heart failure, both MICT and HIIT significantly increased ejection fraction (P < 0.0001) and fractional shortening (MICT: P < 0.001, HIIT: P < 0.0001), and reduced left ventricular end-diastolic and end-systolic dimensions, brain natriuretic peptide (P < 0.0001), and fibrosis (MICT: P < 0.01, HIIT: P < 0.0001); HIIT was even better in reducing brain natriuretic peptide. Myocardial autophagy and mitophagy were compromised in heart failure, and the exercises improved myocardial autophagic flux and mitophagy inconsistently in heart failure with different aetiologies. Significant correlations were found between multiple mitophagy pathways and the cardioprotection of the exercises. Collectively, MICT may be the 'optimum' modality for ischaemic heart failure, while both MICT and HIIT (especially HIIT) were suitable for pressure-overload heart failure. Exercises differently improved myocardial autophagy/mitophagy, and multiple mitophagy-related pathways were closely implicated in cardioprotection of exercises for chronic heart failure.

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Section: Discussionsupporting

confidence: 91%

Exercise training improves cardiac function and regulates myocardial mitophagy differently in ischaemic and pressure‐overload heart failure mice

Guo

Chen

Zhao

et al. 2022

Experimental Physiology

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“…The BCL2 family of proteins, comprising anti-apoptotic and pro-apoptotic members, influences BNIP3-mediated mitophagy [ 60 ]. BNIP3 contains a BH3 domain that enables its interaction with anti-apoptotic BCL2 family members, such as BCL2 and BCL-XL [ 61 ]. This interaction releases the pro-apoptotic protein Beclin-1, initiating autophagy.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury

Chen,

Liu,

Yuan

et al. 2024

BMC Cardiovasc Disord

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Background Myocardial ischemia is a prevalent cardiovascular disorder associated with significant morbidity and mortality. While prompt restoration of blood flow is essential for improving patient outcomes, the subsequent reperfusion process can result in myocardial ischemia–reperfusion injury (MIRI). Mitophagy, a specialized autophagic mechanism, has consistently been implicated in various cardiovascular disorders. However, the specific connection between ischemia–reperfusion and mitophagy remains elusive. This study aims to elucidate and validate central mitophagy-related genes associated with MIRI through comprehensive bioinformatics analysis. Methods We acquired the microarray expression profile dataset (GSE108940) from the Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) using GEO2R. Subsequently, these DEGs were cross-referenced with the mitophagy database, and differential nucleotide sequence analysis was performed through enrichment analysis. Protein–protein interaction (PPI) network analysis was employed to identify hub genes, followed by clustering of these hub genes using cytoHubba and MCODE within Cytoscape software. Gene set enrichment analysis (GSEA) was conducted on central genes. Additionally, Western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) analyses were conducted to validate the expression patterns of pivotal genes in MIRI rat model and H9C2 cardiomyocytes. Results A total of 2719 DEGs and 61 mitophagy-DEGs were identified, followed by enrichment analyses and the construction of a PPI network. HSP90AA1, RPS27A, EEF2, EIF4A1, EIF2S1, HIF-1α, and BNIP3 emerged as the seven hub genes identified by cytoHubba and MCODE of Cytoscape software. Functional clustering analysis of HIF-1α and BNIP3 yielded a score of 9.647, as determined by Cytoscape (MCODE). In our MIRI rat model, Western blot and immunofluorescence analyses confirmed a significant elevation in the expression of HIF-1α and BNIP3, accompanied by a notable increase in the ratio of LC3II to LC3I. Subsequently, qPCR confirmed a significant upregulation of HIF-1α, BNIP3, and LC3 mRNA in the MIRI group. Activation of the HIF-1α/BNIP3 pathway mediates the regulation of the degree of Mitophagy, thereby effectively reducing apoptosis in rat H9C2 cardiomyocytes. Conclusions This study has identified seven central genes among mitophagy-related DEGs that may play a pivotal role in MIRI, suggesting a correlation between the HIF-1α/BNIP3 pathway of mitophagy and the pathogenesis of MIRI. The findings highlight the potential importance of mitophagy in MIRI and provide valuable insights into underlying mechanisms and potential therapeutic targets for further exploration in future studies.

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Enhancing Cardiomyocyte Resilience to Ischemia-Reperfusion Injury: The Therapeutic Potential of an Indole-Peptide-Tempo Conjugate (IPTC)

Hou,

Yan,

Gao

et al. 2024

ACS Omega

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Ischemia/reperfusion (I/R) injury leads to apoptosis and extensive cellular and mitochondrial damage, triggered by the early generation and subsequent accumulation of mitochondrial reactive oxygen species (mtROS). This condition not only contributes to the pathology of I/R injury itself but is also implicated in a variety of other diseases, especially within the cardiovascular domain. Addressing mitochondrial oxidative stress thus emerges as a critical therapeutic target. In this context, our study introduces an indole-peptide-tempo conjugate (IPTC), a compound designed with dual functionalities: antioxidative properties and the ability to modulate autophagy. Our findings reveal that IPTC effectively shields H9C2 cardiomyocytes against hypoxia/reoxygenation (H/R) damage, primarily through counteracting mtROS overproduction linked to impaired mitophagy and mitochondrial dysfunction. We propose that IPTC operates by simultaneously reducing mtROS levels and inducing mitophagy, highlighting its potential as a novel therapeutic strategy for mitigating mitochondrial oxidative damage and, by extension, easing I/R injury and potentially other related cardiovascular conditions.

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JMJD5 attenuates oxygen–glucose deprivation and reperfusion‐induced injury in cardiomyocytes through regulation of HIF‐1α‐BNIP3

Cited by 6 publications

References 29 publications

Exercise training improves cardiac function and regulates myocardial mitophagy differently in ischaemic and pressure‐overload heart failure mice

Exercise training improves cardiac function and regulates myocardial mitophagy differently in ischaemic and pressure‐overload heart failure mice

Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury

Enhancing Cardiomyocyte Resilience to Ischemia-Reperfusion Injury: The Therapeutic Potential of an Indole-Peptide-Tempo Conjugate (IPTC)

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