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Ferroptosis, a newly identified type of programmed cell death type, has been proven to contribute to the progression of myocardial ischemia/reperfusion (I/R) injury. However, little is known about ferroptosis regulation in I/R injury. We identified activating transcription factor 3 (ATF3) as a vital regulator of I/R induced ferroptosis and investigated the effects and potential mechanism of ATF3 in cardiac ferroptosis. In this study, the dynamic RNA-sequencing (RNA-seq) analysis were performed on mouse hearts exposed to different I/R schedules to identify that ATF3 represents an important modulatory molecule in myocardial I/R injury. Then knockout, rescue and overexpression methods were used in mice and neonatal mouse cells (NMCs) to illustrate the effect of ATF3 on myocardial I/R injury. Loss/gain of function techniques were used both in vivo and in vitro to explore the effects of ATF3 on ferroptosis in I/R injury. Furthermore, chromatin immunoprecipitation sequence (ChIP-seq) analysis was performed in the AC16 human cardiomyocyte cell line to investigate potential genes regulated by ATF3. ATF3 expression reached highest level at early stage of reperfusion, knockout of ATF3 significantly aggravated I/R injury, which could be rescued by ATF3 re-expression. Knockout and the re-expression of ATF3 changed the transcription levels of multiple ferroptosis genes. In addition, results showed that overexpression of ATF3 inhibits cardiomyocyte ferroptosis triggered by erastin and RSL3. Lastly, ChIP-seq and dual luciferase activity analysis revealed ATF3 could bind to the transcription start site of Fanconi anaemia complementation group D2 (FANCD2) and increased the FANCD2 promoter activity. Furthermore, we first demonstrated that overexpression of FANCD2 exerts significant anti-ferroptosis and cardioprotective effect on AC16 cell H/R injury. ATF3 inhibits cardiomyocyte ferroptotic death in I/R injury, which might be related with regulating FANCD2. Our study provides new insight into the molecular target for the therapy of myocardial I/R injury. [Display omitted] • ATF3 is a vital regulator during I/R injury. • ATF3 inhibits cardiac ferroptosis in response to I/R injury. • Overexpression of ATF3 could reduce the ferroptotic death of cardiomyocytes induced by erastin and RSL3. • ATF3 could upregulate FANCD2 by directly activating the promoter of FANCD2 in AC16. • FANCD2 exerts significant anti-ferroptosis and protective effects in myocardial H/R injury. [ABSTRACT FROM AUTHOR]

Honokiol (HKL) is a natural low-molecular-weight biphenolic compound derived from the bark of magnolia trees. Previous studies indicate that HKL exerts potent cardioprotective effects on ischemia/reperfusion (I/R) injury; however, evidence of the further relationship between HKL posttreatment and myocardial I/R injury has not been clearly found. In our study, we explored the protective effect of HKL post treatment on myocardial I/R injury in C57BL/6 mice. We also demonstrated that HKL significantly reduced cellular reactive oxygen species production and attenuated mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation (H/R). In addition, HKL was found to enhance autophagy during I/R or H/R; these effects could be partially blocked by the autophagic flux inhibitor chloroquine. Moreover, our results suggested that enhanced autophagic flux is associated with the Akt signaling pathway. Collectively, our results indicate that HKL posttreatment alleviates myocardial I/R injury and suggest a critical cardioprotective role of HKL in promoting autophagic flux. • Honokiol posttreatment ameliorated myocardial ischemia/reperfusion injury. • Honokiol enhanced autophagic flux in NRCs exposed to hypoxia/reoxygenation. • Reducing mitochondrial damage plays an important role in Honokiol cardioprotective effects. • Activation of Akt/ERK signaling is not always good for survival. [ABSTRACT FROM AUTHOR]

Abstract It is widely recognized that inadequate sleep is associated with multiple acute and chronic diseases and results in increased mortality and morbidity for cardiovascular diseases. In recent years, there has been increasing interest in sleep related investigations. Emerging evidence indicates that sleep deprivation changes the biological phenotypes of DNA, RNA and protein levels, but the underlying mechanisms are not clear. We summarized the current research on the detrimental roles of sleep deprivation on the heart and elucidated the underlying mechanisms of sleep deficiency to improve our understanding of sleep deprivation and the emerging strategies to target this process for therapeutic benefit. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction is associated with high rates of morbidity and mortality and can cause irreversible myocardial damage. Timely reperfusion is critical to limit infarct size and salvage the ischemic myocardium. However, reperfusion may exacerbate lethal tissue injury, a phenomenon known as myocardial ischemia/reperfusion (I/R) injury. Pharmacological postconditioning (PPC), a strategy involving medication administration before or during the early minutes of reperfusion, is more efficient and flexible than preconditioning or ischemic conditioning. Previous studies have shown that various mechanisms are involved in the effects of PPC. In this review, we summarize the relative effects and potential underlying mechanisms of PPC to provide a foundation for future research attempting to develop novel treatments against myocardial I/R injury. [ABSTRACT FROM AUTHOR]

Activation transcription factor 3 (ATF3), a member of the ATF/cyclic adenosine monophosphate response element binding family, can be induced by a variety of stresses. Numerous studies have indicated that ATF3 plays multiple roles in the development and progression of cardiovascular diseases, including atherosclerosis, hypertrophy, fibrosis, myocardial ischemia-reperfusion, cardiomyopathy, and other cardiac dysfunctions. In past decades, ATF3 has been demonstrated to be detrimental to some cardiac diseases. Current studies have indicated that ATF3 can function as a cardioprotective molecule in antioxidative stress, lipid metabolic metabolism, energy metabolic regulation, and cell death modulation. To unveil the potential therapeutic role of ATF3 in cardiovascular diseases, we organized this review to explore the protective effects and mechanisms of ATF3 on cardiac dysfunction, which might provide rational evidence for the prevention and cure of cardiovascular diseases. • We elaborated the cardioprotective effects of ATF3 in recent studies. • Our illustration indicates that ATF3 might be a therapeutic target for cardiovascular diseases. • The programmed cell death regulated by ATF3 exerts controversial. [ABSTRACT FROM AUTHOR]