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BACKGROUND: The repair process of myocardial injury involves complex cellular and molecular mechanisms, especially mitochondrial calcium homeostasis, macrophage autophagy and pyroptosis pathways. Traditional Chinese medicine (TCM) has shown significant clinical efficacy in improving myocardial injury, but its mechanism of action needs to be thoroughly investigated. OBJECTIVE: To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury, and to summarize the progress of TCM in this field. METHODS: A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science, PubMed and CNKI. The search terms were “mitochondrial calcium homeostasis, macrophage autophagy, macrophage pyroptosis, traditional Chinese medicine, myocardial injury, myocardial injury reperfusion” in Chinese and English. Through literature review, we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis, explored the mechanism of their roles in myocardial injury, and summarized the pathways of multi-targeted, multipathway effects of TCM. RESULTS AND CONCLUSION: The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes. Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways. Autophagy contributes to cell clearance and regulation of inflammatory response, while pyroptosis affects myocardial repair by releasing inflammatory factors. TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms. For example, astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C, and epimedium glycoside plays a role in reducing β-amyloid deposition. In addition, herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways, such as PI3K/AKT and nuclear factor-κB signaling pathways. Future studies should focus on the interactions between mitochondrial calcium homeostasis, autophagy and pyroptosis pathways, as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects, but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury. Therefore, it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE: To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS: CNKI, WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024. The search terms used were “flap, ischemia-reperfusion injury, inflammatory response, oxidative stress, Ca2+ overload, apoptosis, mesenchymal stem cells, platelet-rich plasma, signaling pathways, shock wave, pretreatment” in Chinese and English. After elimination of irrelevant literature, poor quality and obsolete literature, 77 documents were finally included for review. RESULTS AND CONCLUSION: Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response, oxidative stress response, Ca2+ overload, and apoptosis, which can cause apoptosis of vascular endothelial cells, vascular damage and microcirculation disorders in the flap, and eventually lead to flap necrosis. Studies have found that mesenchymal stem cell transplantation, platelet-rich plasma, signaling pathway modulators, shock waves, and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees, and reduce the necrosis rate and necrosis area of the grafted flap. Although there are many therapeutic methods for skin flap ischemia/reperfusion injury, a unified and effective therapeutic method has not yet been developed in the clinic, and the advantages and disadvantages of various therapeutic methods have not yet been compared. Most of the studies remain in the stage of animal experiments, rarely involving clinical observations. Therefore, a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic. [ABSTRACT FROM AUTHOR]

Introduction: High levels of MG53 may attenuate the damage from myocardial infarction (MI). Furthermore, N6-methyl-adenosine (m6A) methylation is a mode of RNA modification that influences mRNA functions. Whether m6A modification on MG53 exerts a protective role on myocardial injury remains largely unknown. Materials and methods: We established hypoxia/reoxygenation (H/R) H9c2 cell and myocardial ischemia reperfusion (I/R) rat models. MG53 expression was detected using RT-qPCR, and its m6A levels were measured using Me-RIP. The relationship between MG53 and YTHDF2 was evaluated using RNA immunoprecipitation, FISH and immunofluorescence assay, and luciferase reporter assay. MI area of rats was determined using TTC staining. Cell apoptosis was assessed by flow cytometry and TUNEL assay. Results: The m6A levels of MG53 were increased in H/R-induced H9c2 cells and the myocardium of I/R rats. Moreover, knockdown of YTHDF2 recognized the m6A modification of MG53 and enhanced MG53 stability. Overexpression of MG53 inhibited apoptosis of H/R-treated H9c2 cells, which was reversed by YTHDF2, while downregulation of MG53 m6A methylation caused by METTL3 knockdown further abrogated the effect induced by YTHDF2. Additionally, MG53 attenuated MI and apoptosis in I/R rats, which were rescued by YTHDF2. Conclusion: YTHDF2 hinders the protective effect of MG53 on MI by recognizing the m6A modification of MG53. [ABSTRACT FROM AUTHOR]

To investigate the protective role of high dose melatonin concerning myocardial I/R injury and inflammation in patients undergoing on-pump coronary artery bypass grafting (CABG) surgery by evaluating IR/inflammatory biomarkers and clinical outcomes. This was a prospective; randomized; single-blinded placebo-controlled study conducted at cardio-thoracic surgery department of the Academy of the Cardiovascular and Thoracic Surgery, Ain Shams University. Eligible patients were randomly allocated to; melatonin-treated group (MTG) or placebo-treated group (PTG). The MTG (n = 17) received 60 mg/day melatonin capsules daily starting 5 days before surgery in addition to the standard of care. PTG (n = 17) received placebo also 5 days before surgery plus standard of care. The levels of nuclear factor kappa beta (NF-κb) (primary outcome), tumor necrosis factor (TNF-α), cardiac troponins I, and IL-6 levels were all assessed for both groups at five time points: baseline before melatonin or placebo administration (T0), before cross-clamp application(T1), 5 min after cross-clamp removal(T2), 6 h after cross-clamp removal(T3) and 24 h after cross-clamp removal(T4). Blood pressure was assessed at baseline, pre-operative and 24-hours post-operative. The Quality of recovery-40 score (QOR-40) was assessed for both groups on day 4 after surgery. TNF-α levels decreased in the MTG at T1(p = 0.034) versus PTG. At T2(p = 0.005), and T3(p = 0.04), TNF-α significantly increased in PTG versus MTG. Troponins significantly increased in PTG at T3 (p = 0.04) versus MTG. NF-κB levels declined at T1 (p = 0.013) and T2 (p = 0.0001) in MTG compared to PTG. IL-6 significantly increased in PTG versus MTG at T3 (p = 0.04). The QOR-40 score significantly decreased in MTG versus PTG. MTG had statistically significant decrease in DBP compared to the placebo group (p = 0.024). MTG had a statistically significant shorter intubation time than did the placebo group (p = 0.03). Melatonin 60 mg was well-tolerated without any reported side effects. Our findings suggested that melatonin could ameliorate myocardial I/R injury after on-pump CABG and that this outcome was essentially correlated to its antiapoptotic and anti-inflammatory effects. Trial registration: ClinicalTrials.gov registration number NCT05552586, 9/2022. [ABSTRACT FROM AUTHOR]

Interleukin-34 (IL-34) was recently reported to be a new biomarker for atherosclerosis diseases, such as coronary artery disease and vascular dementia. IL-34 regulates the expression of proinflammatory cytokines (IL-17A, IL-1 and IL-6), which are classical cytokines involved in myocardial ischemia‒reperfusion (MI/R) injury. However, the exact role of IL-34 in MI/R remains unknown. In this study, a rat MI/R model was used to explore the effect of IL-34 on modulating inflammatory processes during MI/R injury. First, eighteen rats were subjected to 30 min of LAD ligation followed by 0 h, 1 h, 2 h, 4 h, 8 h or 24 h of reperfusion (n = 3 for each group). The level of IL-34 peaked at 4 h after MI/R in the ischemic myocardium. Next, ischemia for 30min and reperfusion for 4h (I/R) model was used. 24 rats were randomly divided into I/R group (n = 8), IL-34+IR group (n = 8) and IL-34+ab12+IR group (n = 8). We found that IL-34 pretreatment increased the expression of inflammatory cytokines, including high mobility group Box 1 (HMGB1), IL-17A, and IL-6; the expression of the apoptosis protein cleaved caspase-3; and the Bcl-2/Bax ratio within the ischemic myocardium. We also observed increased serum cardiac enzymes and a larger myocardial injury area. Treatment with a Janus kinase (JAK) pathway inhibitor, however, partially reduced the expression of these proteins and attenuated myocardial injury. Together, these results showed that IL-34 aggravates MI/R injury by inducing the expression of the HMGB1-IL-17A-IL-6 axis and apoptosis after MI/R, which is partially dependent on the JAK pathway. Therefore, blocking the JAK signaling pathway or inhibiting IL-34 expression might provide a new idea to reduce MI/R injury, but further researches are needed. [ABSTRACT FROM AUTHOR]

The graphic was created with BioRender.com. [Display omitted] Hepatic ischemia–reperfusion injury (HIRI) is an important cause of liver injury following liver transplantation and major resections, and neutrophils are the key effector cells in HIRI. Double-negative T regulatory cells (DNT) are increasingly recognized as having critical regulatory functions in the immune system. Whether DNT expresses distinct immunoregulatory mechanisms to modulate neutrophils, as in HIRI, remains largely unknown. In this study, we found that murine and human DNT highly expressed CD39 that protected DNT from extracellular ATP-induced apoptosis and generated adenosine in tandem with CD73, to induce high levels of neutrophil apoptosis. Furthermore, extracellular adenosine enhanced DNT survival and suppressive function by upregulating survivin and NKG2D expression via the A2AR/pAKT/FOXO1 signaling pathway. Adoptive transfer of DNT ameliorated HIRI in mice through the inhibition of neutrophils in a CD39-dependent manner. Lastly, the adoptive transfer of A2ar -/- DNT validated the importance of adenosine/A2AR signaling, in promoting DNT survival and immunomodulatory function to protect against HIRI in vivo. In conclusion, purinergic signaling is crucial for DNT homeostasis in HIRI. Augmentation of CD39 or activation of A2AR signaling in DNT may provide novel therapeutic strategies to target innate immune disorders. [ABSTRACT FROM AUTHOR]

The correction notice in the journal "Frontiers in Pharmacology" addresses errors in Figures 3, 4, 5, 7, and 8 of the article "Ginkgolide C alleviates myocardial ischemia/reperfusion-induced inflammatory injury via inhibition of CD40-NF-κB pathway." The corrected figures show the effects of ginkgolide C on infarct size, ultrastructure of myocardial tissue, histopathological changes, and expressions of ICAM-1, VCAM-1, iNOS, CD40, NF-κB, and other proteins in a rat model of myocardial ischemia/reperfusion injury. The authors emphasize that the views expressed in the article are their own and do not necessarily reflect those of their institutions or the publisher. [Extracted from the article]

Increasing evidence shows that inflammation plays a vital role in the occurrence and development of ischemia/reperfusion (I/R). Suppression of excessive inflammation can ameliorate impaired cardiac function, which shows therapeutic potential for clinical treatment of myocardial ischemia/reperfusion (MI/R) diseases. In this study, we investigated whether Ginkgolide C (GC), a potent anti-inflammatory flavone, extenuated MI/R injury through inhibition of inflammation. In vivo , rats with the occlusion of the left anterior descending (LAD) coronary artery were applied to mimic MI/R injury. In vitro , primary cultured neonatal ventricular myocytes exposed to hypoxia/reoxygenation (H/R) were applied to further discuss the anti-H/R injury property of GC. The results revealed that GC significantly improved the symptoms of MI/R injury, as evidenced by reducing infarct size, preventing myofibrillar degeneration and reversing the mitochondria dysfunction. Moreover, histological analysis and Myeloperoxidase (MPO) activity measurement showed that GC remarkably suppressed Polymorphonuclears (PMNs) infiltration and ameliorated the histopathological damage. Furthermore, GC pretreatment was shown to improve H/R-induced ventricular myocytes viability and enhance tolerance of inflammatory insult, as evidenced by suppressing expression of CD40, translocation of NF-κB p65 subunit, phosphorylation of IκB-α, as well as the activity of IKK-β. In addition, downstream inflammatory cytokines modulated by NF-κB signaling were effectively down-regulated both in vivo and in vitro , as determined by immunohistochemistry and ELISA. In conclusion, these results indicate that GC possesses a beneficial effect against MI/R injury via inflammation inhibition that may involve suppression of CD40-NF-κB signal pathway and downstream inflammatory cytokines expression, which may offer an alternative medication for MI/R diseases. [ABSTRACT FROM AUTHOR]

Purpose: Due to its increased volume, polycystic ovarian tissue is more prone to torsion than normal ovarian tissue. In treating ovarian torsion, detorsion is applied to ensure oxygenation of hypoxic tissues. However, the resulting oxygen radicals cause tissue damage. Bromelain is a substance obtained from pineapple, and studies in the literature show it is used as an antioxidant. This study aimed to evaluate the damage caused by ischemia-reperfusion (I/R) in the torsion-detorsion model created in normal and polycystic ovarian tissue and investigate the role of bromelain in this damage. Methods: Polycystic ovarian tissue was created by applying dihydroepiandrosterone sulfate to rats. Afterward, a torsion-detorsion model was used for all rats. The rats were divided into six groups: the polycystic ovary sham-operated group (P-S), the normal ovary sham-operated group (N-S), the polycystic ovary ischemia/reperfusion group (P-IR), the normal ovary ischemia/reperfusion group (N-IR), the polycystic ovary ischemia/reperfusion group treated with bromelain (P-IRB), and the normal ovary ischemia/reperfusion group treated with bromelain (N-IRB). After the procedure, tissues were collected for histopathological examination, and MDA, TUNEL, and NF-κB levels were measured. Results: This study detected significant decreases in MDA and NF-κB levels and apoptotic cell numbers assessed by TUNEL staining in groups with IR damage and given bromelain compared to the control groups. The number of TUNEL-positive cells was found to be highest in the P-IR group (8.80 ± 2.98) and significantly lower in the bromelain-administered P-IRB (1.04 ± 1.09) and N-IRB (0.52 ± 0.58) groups (p< 0.05). NF-κB expression was also high in P-IR and N-IR groups, while it was significantly decreased in bromelain-treated groups (P-IRB and N-IRB) (p< 0.05). In addition, IR damage was more pronounced in polycystic ovary tissue than in normal ovary tissue. Conclusion: Ischemia perfusion damage may be more pronounced in polycystic ovarian tissue than in normal ovarian tissue. Bromelain may be preferred to prevent I/R injury caused by ovarian torsion. It is also thought that bromelain may function in treating polycystic ovaries, and further studies can be conducted on this subject. [ABSTRACT FROM AUTHOR]

As an important element of the human body, iron participates in numerous physiological and biochemical reactions. In the past decade, ferroptosis (a form of iron-dependent regulated cell death) has been reported to contribute to the pathogenesis and progression of various diseases. The stability of iron in cardiomyocytes is crucial for the maintenance of normal physiological cardiac activity. Ferroptosis has been detected in many cardiovascular diseases (CVDs), including coronary heart disease, myocardial ischemia–reperfusion injury, heart failure, and chemotherapy-induced myocardial damage. In cardiomyocytes, epigenetic regulation and post-translational modifications regulate the expression of ferroptosis-related factors, maintain iron homeostasis, and participate in the progression of CVDs. Currently, there is no detailed mechanism to explain the relationship between epigenetic regulation and ferroptosis in CVDs. In this review, we provide an initial summary of the core mechanisms of ferroptosis in cardiomyocytes, with first focus on the epigenetic regulation and expression of ferroptosis-related factors in the context of common cardiovascular diseases. We anticipate that the new insights into the pathogenesis of CVDs provided here will inspire the development of clinical interventions to specifically target the active sites of these factors, reducing the harmfulness of ferroptosis to human health. [ABSTRACT FROM AUTHOR]

The study aimed to elucidate the underlying pharmacological mechanism of the traditional Chinese medicine Pue in ameliorating myocardial ischemia-reperfusion injury (MIRI), a critical clinical challenge exacerbated by reperfusion therapy. In vivo MIRI and in vitro anoxia/reoxygenation (A/R) models were constructed. The results demonstrated that Pue pretreatment effectively alleviated MIRI, as manifested by diminishing the levels of serum CK-MB and LDH, mitigating the extent of myocardial infarction and enhancing cardiac functionality. Additionally, Pue significantly alleviated histopathological damage in MIRI-treated myocardium, as evidenced by HE staining and TUNEL assay. In vitro, Pue pretreatment significantly alleviated A/R-induced damage by decreasing LDH levels, increasing cellular activity, inhibiting autophagic lysosomal overactivation, inhibiting oxidative stress (ROS, LIP ROS, MDA), increasing antioxidant defense (SOD, GSH-Px), and increasing P62 protein expression while decreasing LC3II/I ratio. Furthermore, Pue inhibited apoptosis and maintained mitochondrial homeostasis by up-regulating the expression of Hairy and Enhancer of Split-1 (HES1) protein, which was crucial for its cardioprotective effects. Nevertheless, the cardioprotective efficacy of Pue pretreatment was negated via the knockdown of HES1 protein expression via pAD/HES1-shRNA transfection. In conclusion, Pue effectively ameliorated HES1-mediated MIRI-induced autophagy, apoptosis, and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

The article explores the potential of tetrahydrocannabinol (THC) as a drug for modulating post-ischemic inflammation and restoring myocardial function in patients with coronary artery disease (CAD). The study investigates the involvement of the endocannabinoid system (ECS) in the inflammatory response to myocardial ischemia and reperfusion, with a focus on selective modulation for the heart. Findings suggest that THC, a specific cannabinoid receptor-2 (Cnr2) agonist, may have a therapeutic role in treating CAD-related myocardial dysfunction. The research highlights the relevance of the ECS in mediating inflammatory responses and offers a new perspective on anti-inflammatory therapy for CAD patients. [Extracted from the article]

The document provides abstracts from the 28th Congress of the Spanish Society for Surgery Research in 2024, covering a wide range of topics such as implantable devices for drug delivery, flow dynamics simulation, soft skills training in residency, nerve regeneration, and vascular graft studies. Research includes investigations into treatments for myocardial infarction, vascular graft development, and the therapeutic use of menstrual blood-derived stromal cells for heart attack management. Other studies focus on predicting small intestine length for bariatric surgery, predictive algorithms for bariatric surgery, advanced therapies for post-myocardial infarction ventricular dysfunction, and surgical skills training in fetoscopy and fetal surgery. The document also delves into laparoscopic ureteral obstruction modeling, artificial intelligence in robotic surgery education, vascular graft validation, endovascular procedures for stroke in large animals, and bioinformatic analyses on the therapeutic potential of secretomes from menstrual blood-derived stromal cells. [Extracted from the article]

Objective(s): Ischemia/reperfusion (IR)-induced ventricular arrhythmia, which mainly occurs after the opening of coronary artery occlusion, poses a clinical problem. This study aims to investigate the effectiveness of pretreatment with coenzyme Q10 (CoQ10) in combination with mitochondrial transplantation on IR-induced ventricular arrhythmias in aged rats. Materials and Methods: Myocardial IR induction was performed by left anterior descending coronary artery occlusion for 30 min, followed by re-opening for 24 hr. CoQ10 was administered intraperitoneally at a dosage of 10 mg/kg/day for two weeks before inducing IR. At the start of reperfusion, 500 µl of the respiration buffer containing 6x106±5x105 mitochondria/ml of respiration buffer harvested from the pectorals major muscle of young donor rats were injected intramyocardially. To investigate arrhythmias, the heart's electrical activity during ischemia and the first 30 min of reperfusion were recorded by electrocardiogram. After 24 hr of reperfusion, cardiac histopathological changes, creatine kinase-MB, nitric oxide metabolites (NOx), oxidative stress markers (malondialdehyde, total antioxidant, superoxide dismutase, and glutathione peroxidase), and the expression of genes regulating mitochondrial fission/fusion were measured. Results: Pretreatment with CoQ10 in combination with mitochondrial transplantation reduced ventricular arrhythmias, cardiac histopathological changes, and creatine kinase-MB levels. Simultaneously, this combined therapeutic approach increased myocardial NOx levels, fostering an improved oxidative balance. It also triggered the down-regulation of mitochondrial fission genes, coupled with the up-regulation of mitochondrial fusion genes. Conclusion: The combination of CoQ10 and mitochondrial transplantation demonstrated a notable anti-arrhythmic effect by elevating NOx levels, reducing oxidative stress, and improving mitochondrial fission/fusion in aged rats with myocardial IRI. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion injury (MIRI) is a serious clinical complication that is caused by reperfusion therapy following myocardial infarction (MI). Mitochondria-related genes (Mito-RGs) play important roles in multiple diseases. However, the role of mitochondria-related genes in MIRI remains largely unknown. The GSE67308 dataset from the GEO database was utilized to identify MIRI-related gene modules through WGCNA. Meanwhile, differential expression analysis was conducted to identify differentially expressed genes (DEGs) in the GSE61592 dataset. Next, candidate Mito-RGs related to MIRI were screened by Venn analysis. Thereafter, a myocardial hypoxia/reperfusion (H/R) H9C2 cell model and a mouse ischemia/reperfusion (I/R) model were established to verify the expression level of glycine decarboxylase (Gldc) in MIRI in vitro and in vivo. Based on data from the GEO database, Gldc levels were notably upregulated in murine MIRI samples, compared to the control group. RT-qPCR and western blot confirmed that Gldc levels were obviously elevated in the heart of I/R mice and H/R-exposed cardiomyocytes. Moreover, the deficiency of Gldc notably increased the viability and reduced the apoptosis and inflammatory responses in H9C2 cells exposed to H/R. Meanwhile, Gldc downregulation significantly reduced p-NF-κB p65, Bax and cleaved caspase 3 levels and elevated p-Akt and Bcl-2 levels in H9C2 cells exposed to H/R. The ROC curve analysis further demonstrated that Gldc gene exhibited good diagnostic value for MIRI. Collectively, Gldc deficiency could attenuate H/R injury in cardiomyocytes in vitro through activating Akt and inactivating NF-κB signalings. These data suggested that GLDC may serve as both a diagnostic and therapeutic target for MIRI. [ABSTRACT FROM AUTHOR]

Myocardial dysfunction is a major cause of early mortality after successful cardiopulmonary resuscitation (CPR) following cardiac arrest (CA). Following the return of spontaneous circulation, myocardial ischemia–reperfusion injury can activate the NF-κB pathway, leading to the transcription of inflammatory genes that impair myocardial function. While clinical studies show hydrocortisone (HC) improves outcomes in CA patients during CPR, its specific role in modulating the NF-κB pathway is unclear. In this study, we established an in vitro model by inducing hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes using Na2S2O4, followed by HC treatment. The results showed that HC treatment of H/R-injured cardiomyocytes promoted proliferation, inhibited apoptosis, and suppressed the NF-κB pathway, thereby reducing interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) levels. Moreover, inhibition of the NF-κB pathway enhanced the proliferative capacity of H/R cardiomyocytes, decreased apoptosis rates, and reduced IL-6, IL-8, and TNF-α expression levels, with these effects being further amplified by HC treatment. These findings were further supported by in vivo experiments. In conclusion, our study suggests that HC may promote H/R cardiomyocyte proliferation, inhibit apoptosis, and alleviate inflammatory responses by suppressing the NF-κB pathway, providing new evidence to support its potential clinical application in CA management. [ABSTRACT FROM AUTHOR]

Myocardial ischemia-reperfusion injury (MIRI) injury is a serious health problem, which can seriously affect the recovery of patients with myocardial infarction and even lead to death. Paeoniflorin (PF) is a potential therapeutic drug to prevent reperfusion injury. However, the mechanism of PF in MIRI is not clear. Compared with other cells, cardiomyocytes have the largest number of mitochondria. Therefore, this study researched the protective mechanism of paeoniflorin pretreatment on myocardial ischemia-reperfusion injury (AMI) from the perspective of mitochondrial autophagy. Paeoniflorin was given or not given to H9C2 cells 12 h before reperfusion. Pretreatment of paeoniflorin can significantly increase the viability of H9C2 cells and inhibit the increase of ROS secretion induced by OGD/R. The increase of MDC autophagy fluorescence and mitochondrial membrane potential (MMP) suggested that the myocardial protective effect of paeoniflorin may also be related to mitochondrial autophagy. Next, we detected the related signals in the classical mitochondrial autophagy pathway of PINK1/parkin by Q-PCR and Western blots. The results showed that the pretreatment of paeoniflorin could promote the levels of SIRT1, Beclin1, PINK1, parkin and LC3, inhibit the level of P62. In order to further clarify whether paeoniflorin-induced SIRT1 activation is necessary for autophagy and its potential mechanism, we detected the autophagy level of H9C2 cells with SIRT1 inhibitor (EX527). The results showed that after pretreatment of EX527, the protective effect of paeoniflorin on oxidative damage and autophagy pathway was significantly decreased. The mechanism may relate to SIRT1-PINK1/parkin mitochondrial autophagy pathway. In summary, these results suggested that paeoniflorin may protect H9C2 cells from OGD/R damage by activating SIRT1-PINK1/parkin pathway. This provides new experimental basis for paeoniflorin in the treatment of MIRI. [Display omitted] • Paeoniflorin promotes autophagy of H9C2 cells and reduce mitochondrial dysfunction • Paeoniflorin protects cells from OGD/R-induced reperfusion injury through PINK1/parkin mitochondrial autophagy. • Paeoniflorin activates PINK1/parkin pathway by regulating the expression of SIRT1, which can protect H9C2 cells from OGD/R-induced reperfusion injury. [ABSTRACT FROM AUTHOR]

Splenic nerve neuromodulation improved pathological remodeling by limiting CCR2 and pro-inflammatory cytokines in acute and chronic myocardial ischemic injury. The heart might have adverse cardiac remodeling and gradually developed into HF, mainly characterized by cardiomyocyte depletion, macrophage infiltration, fibroblast proliferation, collagen deposition and sympathetic activation, after either acute myocardial IRI or chronic MI. By histological sequencing and biological verification, downregulation of CCR2 and proinflammatory cytokines might the potential mechanism of SpNS on acute and chronic myocardial ischemic injury. IRI, ischemia–reperfusion injury; MI, myocardial infraction; SpNS, electrical splenic nerve stimulation; SpN, splenic nerve; cholinergic anti-inflammatory pathway, CAIP; NE, norepinephrine; Ach, acetylcholine; ChAT, choline acetyltransferase. [Display omitted] • The negative regulation of chemokine production pathway was significantly enriched between the IRI and IRI + SpNS group. • Splenic nerve neuromodulation exerts its protective effect against myocardial IRI through downregulating CCR2. • SpNS significantly alleviated cardiac remodeling and improved left ventricle systolic function at 4 weeks post-MI by downregulating CCR2. • Splenic nerve neuromodulation could be a promising therapeutic approach for MI patients. Pathological remodeling after myocardial infarction (MI) confers the development of heart failure. Our prior research has indicated that splenic nerve neuromodulation mitigates myocardial ischemia–reperfusion injury (IRI) by reducing levels of proinflammatory factors. This study aims to explore the potential therapeutic benefits of splenic nerve neuromodulation in MI and the underlying mechanism. Splenic nerve neuromodulation was performed through electrical splenic nerve stimulation (SpNS). In the acute myocardial IRI model, post-mortem analyses encompassed RNA sequencing and a range of molecular biology techniques, with the application of CCR2 antagonists (RS-504393) to inhibit the CCR2. In the chronic MI model, rats underwent echocardiographic assessment four weeks post-MI, after which tissues were harvested. In the acute IRI model, the negative regulation of chemokines production pathway was enriched by RNA-seq, and SpNS reduced the levels of CCR2, CCL2, and CCL7. The administration of RS-504393 decreased cardiomyocyte apoptosis, reduced myocardial damage, and lowered proinflammatory cytokines levels following myocardial IRI. Additionally, SpNS was shown to inhibit oxidative stress, proinflammatory cytokine levels, and cardiac collagen deposition, as observed four weeks post-MI. SpNS also restrained sympathetic nerve remodeling and improved left ventricular function, in part by downregulating CCR2 in the chronic MI model. SpNS demonstrated significant improvements in cardiac function, reductions of cardiac remodeling and inhibitions of excessive sympathetic activation in the chronic MI model by downregulation of CCR2. Our study provides novel evidence that splenic nerve neuromodulation may serve as a potential therapeutic intervention in MI patients. [ABSTRACT FROM AUTHOR]

The aim of this study is to examine the impact of controlled stepwise reperfusion by modulating pre-dilation balloon pressure during primary percutaneous coronary interventions (PPCI) in patients with ST-elevation myocardial infarction (STEMI).Consecutive STEMI patients requiring PPCI with thrombolysis in myocardial infarction (TIMI) flow grades 0 or 1, were randomly divided into an experimental group and a control group. For the control group, the pre-dilation balloon was removed immediately after achieving antegrade perfusion beyond the lesion. The experimental group underwent stepwise reperfusion, with the balloon pressure being gradually reduced. Baseline data, intra/post-procedural PPCI data, 3-month left ventricular ejection fraction (LVEF), and major adverse cardiac events (MACE) were documented and compared between the two groups.The control group experienced more severe symptoms during the procedure (p = 0.034), higher post-procedural corrected TIMI frame counts (p = 0.047), more significant hemodynamic changes (p = 0.031), and increased rates of ventricular tachycardia/ventricular fibrillation (p = 0.035). Additionally, they had a higher total number of arrhythmias (p = 0.017), a lower 90-min ST segment resolution rate (p = 0.045), and elevated cTNI levels one week after the procedure (p = 0.047). Three months later, the control group demonstrated a lower LVEF compared to the experimental group (p = 0.048) and a trend towards more drug-treated arrhythmias (p = 0.073). No differences were observed in other statistical results.In patients with STEMI undergoing PPCI, controlled stepwise reperfusion by adjusting the pre-dilation balloon pressure effectively reduces myocardial ischemia-reperfusion injury, improves myocardial perfusion, and supports the recovery of cardiac function. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to explore the protective mechanism of proline hydroxylase (PHD) in reducing myocardial ischemia-reperfusion injury (MIRI) through the hypoxia-inducible factor (HIF)-1α-adenosine-MAPK/ERK signaling pathway, with the goal of identifying potential drug targets and therapeutic strategies for the clinical management of MIRI. Methods: A rat model of MIRI was established using 45 male Sprague-Dawley (SD) rats, which were randomly divided into the following three groups: sham operation (n = 15), MIRI model (n = 15), and MIRI + FG-4592 preconditioning (n = 15) groups. Cardiac function was assessed by echocardiographic measurements of the left ventricular end-diastolic diameter (LVIDd), left ventricular contractile diameter (LVIDs), left ventricular shortening fraction (FS), and left ventricular ejection fraction (EF). Cardiomyocyte apoptosis was evaluated using hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Myocardial infarct size was determined with 23,5-triphenyltetrazolium chloride (TTC) staining, while levels of inflammatory factors such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were quantified using enzyme-linked immunosorbent assays (ELISA). Western blot (WB) analysis was performed to assess the expression of apoptotic proteins ERK1/2, phosphorylated-ERK1/2 (p-ERK1/2), AKT, phosphorylated-AKT (p-AKT), caspase-3, BCL-2, and BAX in the infarct boundary area. Adenosine levels within myocardial tissue were also measured. Results: FG-4592 preconditioning significantly improved cardiac function, lowered cardiomyocyte apoptosis and myocardial infarction size, reduced myocardial tissue damage, and inhibited inflammation. Additionally, FG-4592 increased the expression of anti-apoptotic proteins and enhanced adenosine levels in myocardial tissue in the treatment group compared with the MIRI model group. Conclusions: Inhibition of HIF-1α degradation plays a significant role in enhancing extracellular adenosine levels and reducing MIRI, possibly regulating apoptosis through the MAPK/ERK signaling pathway. These findings highlight the potential of targeting the PHD-HIF-adenosine axis in developing treatment strategies for MIRI, meriting future exploration. [ABSTRACT FROM AUTHOR]

Sympathetic nervous system (SNS), endothelin 1 (ET-1) and angiotensin II (Ang II) are involved in the pathophysiology of acute myocardial infarction (AMI). Valproic acid (VPA) is under study for the treatment against AMI due to its beneficial cardiac effects. However, the vascular effects of VPA on the activation of the SNS, ET-1 and Ang II after AMI are not fully studied. In our study, we used aorta from New Zealand White rabbits without AMI, with AMI and AMI treated with VPA (500 mg/kg/day). AMI was induced by occluding the left circumflex coronary artery for 1 h, followed by reperfusion. After 5 weeks, we studied the ex vivo vascular reactivity in organ bath and measured protein expression by Western blot. Our findings indicated that AMI increased vasoconstriction to exogenous and endogenous NE and ET-1, which was reversed by VPA eliciting upregulation of α 2 -adrenergic and ETB receptors and downregulating ETA receptors. Although no changes in the vascular response to Ang II were observed in AMI or VPA-treated rabbits, an increase in Ang II type 2 receptor expression was found in VPA-treated rabbits. We conclude that VPA could be considered a vascular protector by modulating SNS, ET-1 and Ang II in the aorta, which together with its cardioprotective effect would make it a promising candidate for the treatment of AMI. [Display omitted] • ET-1 and SNS are activated after AMI causing hypercontractility. • VPA reverses the AMI-induced hypercontractility in response to NE and ET-1. • VPA upregulates α 2 -adrenergic, ETB and Ang II type 2 receptors. • VPA could be vascular protective after AMI. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been reported as successful for preventing doxorubicin (DOX) -induced cardiotoxicity (DIC), but the underlying mechanisms are elusive. This study aimed to determine whether canagliflozin, an SGLT2i, protects against DIC by regulation of autophagic flux in cardiomyocytes through a mechanism independent of SGLT2. The differentially expressed autophagy-related genes (ARGs) in DIC were analyzed. Neonatal rat cardiomyocytes (NRCMs), H9C2 rat cardiomyocytes or C57BL/6 mice were treated with canagliflozin or vehicle. The effects on cellular apoptosis and autophagy were investigated using qRT-PCR, western blotting and immunofluorescence. Additionally, cardiac function, myocardial fibrosis, and apoptosis of cardiomyocytes were also assessed in mice. The potential molecular targets of canagliflozin were identified through molecular docking analysis. A total of 26 differentially expressed ARGs were identified. Canagliflozin significantly activated autophagic flux and inhibited apoptosis of cardiomyocytes in both DOX-treated H9C2 rat cardiomyocytes and NRCMs. In a murine model of DIC, canagliflozin improved cardiac dysfunction by suppressing cardiac remodeling, fibrosis, and apoptosis. Moreover, canagliflozin promoted autophagy by enhancing SIRT1 levels and inhibiting the PI3K/Akt/mTOR signaling pathway. Immunofluorescence assays revealed that canagliflozin promoted the translocation of LC3 from the nucleus to the cytoplasm. Molecular docking analysis confirmed that canagliflozin has high affinity for targets associated with DIC. These findings suggest that canagliflozin protects cardiomyocytes from DOX-induced cell death by activating SIRT1, inhibiting the PI3K/Akt/mTOR pathway, and enhancing autophagic flux. [Display omitted] • Canagliflozin exerts a protective effect on DIC by regulating autophagic flux. • Canagliflozin protects cardiomyocytes against apoptosis by activating SIRT1. • Targets associated with DIC as mTOR have good affinity with Canagliflozin. [ABSTRACT FROM AUTHOR]

Ferroptosis is a key process in doxorubicin (DOX)-induced cardiotoxicity and is a potentially important therapeutic target. Thymoquinone (TQ) is a monoterpenoid compound isolated from black cumin extract that exhibits antitumor effects and acts as a powerful mitochondrial-targeted antioxidant. In this study, we investigated the effect of TQ on DOX-induced cardiotoxicity and the potential underlying mechanisms. Mice were randomly assigned to the control (CON) group, DOX (20 mg/kg) group, TQ10 (10 mg/kg/d) group, and TQ20 (20 mg/kg/d) group and intraperitoneally injected with DOX and different doses of TQ. The electrocardiogram, blood pressure, and cardiac ultrasound changes during the experiments showed that TQ exerted a protective effect against DOX-induced cardiotoxicity. The glutathione (GSH), malondialdehyde (MDA), and total antioxidant capacity (T-AOC) levels in the mouse heart tissue were significantly different from those in the CON group. Western blot analysis revealed that the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) in the DOX group was lower than that in the control group. TQ treatment decreased these changes, indicating that TQ alleviated DOX-induced cardiotoxicity and increased the antioxidant capacity of murine cardiomyocytes. The mechanism might involve activating the Nrf2/HO-1 signaling pathway and reducing iron-mediated death. Immunohistochemical staining revealed similar effects on the expression levels of NQO1, COX-2, and NOX4. Moreover, transmission electron microscopy indicated that TQ protected murine cardiomyocytes against DOX-induced mitochondrial damage. The results of this study suggested that TQ can decrease oxidative stress levels and DOX-induced cardiotoxicity by activating the Nrf2/HO-1 signaling pathway to alleviate ferroptosis in murine cardiomyocytes. • We found for the first time that thymoquinone can alleviate doxorubicin-induced cardiac toxicity in mice. • Thymoquinone may alleviate iron death in mouse cardiomyocytes by activating the Nrf2/HO-1 signaling pathway. • Thymoquinone can also alleviate oxidative stress in mouse cardiomyocytes. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury is closely linked to oxidative stress, which arises from the complicated metabolism of substances and energy. There is a growing inclination towards developing and applying fluorescent probe tools to explore this phenomenon's physiological and pathological mechanisms. Starting from the pathophysiology of ischemia-reperfusion injury in various organs, this review will provide a comprehensive overview of the research advancements related to developing and applying fluorescence probes for studying ischemia-reperfusion diseases. We will examine the use of small molecule fluorescence probes in the context of ischemia-reperfusion in various tissues and organs. Our focus will include liver, brain, kidney, and myocardial ischemia-reperfusion and other related conditions. In addition, this comment will deeply reflect on and analyze the development direction of fluorescent probes for ischemia-reperfusion injury, highlighting their potential for accurate clinical diagnosis and application research. This discussion aims to inspire hope and optimism in the audience about the future of medical research. [Display omitted] • This review will provide a comprehensive overview of studying ischemia-reperfusion diseases employing fluorescent probe. • The fluorescent probe imaging in liver, brain, kidney, and myocardial ischemia-reperfusion and other related conditions. • This review highlights fluorescent probe potential for accurate clinical diagnosis and application research. [ABSTRACT FROM AUTHOR]

Autophagy is a well-conserved self-protection process that plays an important role in cardiovascular diseases. Excessive autophagy during myocardial ischemia/reperfusion injury (MIRI) induces calcium overload and the overactivation of an autophagic response, thereby aggravating cardiomyocyte damage. Polycystin-2 (PC2) is a Ca2+-permeable nonselective cation channel implicated in the regulation of autophagy. In the present study, autophagy was upregulated in myocardial ischemia/reperfusion in vivo and in vitro. PC2 knockdown using adeno-associated virus 9 particles containing Pkd2 short hairpin RNA infection markedly ameliorated MIRI, evidenced by reduced infarct size, diminished morphological changes, decreased cTnI levels, and improved cardiac function. Silencing PC2 reduced the autophagic flux in H9c2 cells. PC2 overexpression-mediated autophagic flux was inhibited by intracellular Ca2+ chelation with BAPTA-AM. Furthermore, PC2 ablation upregulated p-Akt (Ser473) and downregulated Beclin 1 in H/R. BAPTA-AM downregulated p-Akt(Ser473) and upregulated Beclin 1in PC2-overexpressing H9c2 cells. Moreover, the Akt inhibitor MK2206 abolished the BAPTA-AM-blunted PC2-dependent control of autophagy. Collectively, these results indicated that blockade of PC2 may be associated with the Ca2+/Akt/Beclin 1 signaling, thereby inhibiting excessive autophagy and serving as a potential strategy for mitigating MIRI. [Display omitted] • Myocardial H/R and I/R enhanced the expression of PC2. • Knockdown of PC2 expression reduced H/R induced autophagy autophagic flux. • Blockage of PC2 attenuated the MIRI by inhibiting excessive autophagy through Ca2+/Akt/Beclin 1 signaling axis. [ABSTRACT FROM AUTHOR]

• Ferroptosis is involved in myocardial injury and malignant VAs after myocardial I/R. • USP38-CKO ameliorated myocardial injury and reduced susceptibility to VAs after myocardial I/R, whereas USP38-TG had the opposite effect. • USP38 mediates ferroptosis through the P53-SLC7A11 pathway thereby affecting myocardial injury and susceptibility to VAs after I/R. Myocardial ischemia–reperfusion (I/R) leads to myocardial injury and malignant ventricular arrhythmias (VAs). Ferroptosis is a novel form of cell death that plays a role in myocardial injury after I/R. Ubiquitin-specific protease 38 (USP38), a member of the deubiquitinating enzyme family, is involved in regulating the progression of inflammation and tumors, but its role in myocardial I/R and ferroptosis is unclear. Herein, we explored whether USP38 regulates myocardial I/R-induced ferroptosis and the development of malignant arrhythmias and underlying mechanisms. In this study, cardiac I/R mice model was established by ligating/loosening the left anterior descending artery, and the effects of USP38 on I/R-induced ferroptosis and VAs susceptibility were investigated using USP38 cardiac conditional knockout (USP38-CKO) mice and USP38 cardiac specific overexpression (USP38-TG) mice. In addition, an in vitro I/R model was constructed by hypoxia/reoxygenation (H/R) for further validation. Our study showed that USP38 expression was significantly increased after I/R. USP38-CKO significantly inhibited I/R-induced iron overload, ROS production, and lipid peroxidation. In addition, USP38-CKO ameliorates post-I/R electrophysiologic abnormalities and reduces susceptibility to VAs. USP38-TG showed the opposite effect, exacerbating ferroptosis and increasing susceptibility to VAs after I/R. In vivo experiments similarly demonstrated that USP38 significantly exacerbated H/R-induced ferroptosis. Mechanistically, USP38 directly interacts with P53 and regulates the ubiquitination level of P53 and downstream SLC7A11 expression. We found that ferroptosis was significantly associated with VAs after I/R. USP38 can modulate myocardial injury and VAs susceptibility by affecting ferroptosis, which may be related to the P53/SLC7A11 pathway. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is one of the most severe cardiovascular diseases (CVD). Traditional Chinese medicines have unique advantages in the treatment of CVD, with Xin-Ke-Shu (XKS) being a commonly used Chinese patent medicine for the prevention and treatment of MI patients. This study aimed to investigate the dynamic metabolic profiles of plasma and urine in left anterior descending coronary artery ligation (LAD) -induced MI rats at days 3, 12, and 21 after surgery, and to evaluate the regulatory effects of XKS at these time points using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics. The metabolic profiles of plasma and urine in the LAD-induced MI rats showed significant variations at days 3, 12, and 21 after MI. We identified a total of 23 plasma metabolites and 12 urine metabolites as potential pathological markers related to MI progression. These metabolites were mainly involved in pathways such as TCA cycle, arachidonic acid metabolism, glutathione metabolism, glycerophospholipid metabolism, sphingolipid metabolism, and fatty acid metabolism, all of which were associated with imbalance of myocardial energy metabolism, oxidative stress, and calcium overload. Disturbances in the TCA cycle, arachidonic acid metabolism, glutathione metabolism, and purine metabolism in plasma and urine were observed as early as day 3 after MI. By day 12, we noted significant changes in fatty acid metabolism in plasma and urine, along with notable alterations in sphingolipid metabolism in plasma. Disorders in plasma glycerophospholipid metabolism were first evident at day 12 and reached their peak severity by day 21. Treatments with XKS significantly regulated the disturbances in the plasma and urine metabolic profiles of MI rats at days 3, 12, and 21, with medium dose of XKS displaying a particularly strong regulatory effect, especially at day 12. Our study demonstrates that host metabolism undergoes dynamical changes following MI with most metabolic disorders manifesting in the early stage of MI. XKS effectively regulates nearly all of these disturbances and can be administered as soon as possible after MI. These findings provide valuable insights into the metabolic progression of MI and highlight the therapeutic potential of XKS in the treatment of MI. [Display omitted] • Plasma and urine metabolic profiles in MI rats show different on days 3, 12 and 21. • TCA cycle and arachidonic acid metabolism in MI rats were disturbed earlier (day 3). • Fatty acid and lipid metabolisms in MI rats were disturbed later (day 12). • XKS dynamically regulated the metabolic disturbances in different stages of MI. [ABSTRACT FROM AUTHOR]

High-altitude cardiac injury is a prevalent form of tissue damage resulting from hypobaric hypoxia (HH). MICU1 is a critical modulator of mitochondrial calcium uptake, with significant implications for the regulation of mitochondrial redox homeostasis. This study sought to examine the impact of MICU1 and elucidate the underlying mechanism in myocardial exposed to HH. Loss-and gain-of-function approaches were used to investigate the role of MICU1 in cardiac response to HH. In vitro, the function of MICU1 in the primary neonatal rat cardiomyocytes under hypoxia was examined. We observed that MICU1 was downregulated in hearts exposed to HH, contributing to myocardial apoptosis. In vitro experiments demonstrated that MICU1 knockdown exacerbated hypoxic cardiomyocyte injury, as evidenced by an increase in apoptotic cells and a decrease in mitochondrial membrane potential. Conversely, overexpression of MICU1 in mice significantly mitigated myocardial injury, leading to enhanced cardiac function and reduced myocardial hypertrophy and fibrosis in hypobaric hypoxic mice, consistent with the in vitro findings. Further investigations revealed that overexpression of MICU1 inhibited apoptosis by augmenting mitochondrial Ca2+ uptake and subsequently enhancing the activity of tricarboxylic acid cycle (TCA) related enzymes. Lastly, our results suggest that hypoxia-induced downregulation of MICU1 is mediated by the reduction of MAZ expression in primary neonatal rat cardiomyocytes. Our results suggest that MICU1 plays an important role in myocardial protection subjected to HH, suggesting that enhancing the expression or activity of MICU1 may be a potential pharmacological target to ameliorate myocardial injury at high altitude. • MICU1 was downregulated in hearts subjected to HH. • Upregulation of MICU1 ameliorated cardiac hypertrophy and fibrosis in HH-exposed mice. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is linked to myocardial ischemia-reperfusion (I/R) injury. Checkpoint kinase 1 (CHK1) could facilitate cardiomyocyte proliferation, however, its role on mitochondrial function in I/R injury remains unknown. To investigate the role of CHK1 on mitochondrial function following I/R injury, cardiomyocyte-specific knockout/overexpression mouse models were generated. Adult mouse cardiomyocytes (AMCMs) were isolated for in vitro study. Mass spectrometry-proteomics analysis and protein co-immunoprecipitation assays were conducted to dissect the molecular mechanism. CHK1 was downregulated in myocardium post I/R and AMCMs post oxygen-glucose deprivation/re‑oxygenation (OGD/R). In vivo , CHK1 overexpression protected against I/R induced cardiac dysfunction, while heterogenous CHK1 knockout exacerbated cardiomyopathy. In vitro , CHK1 inhibited OGD/R-induced cardiomyocyte apoptosis and bolstered cardiomyocyte survival. Mechanistically, CHK1 attenuated oxidative stress and preserved mitochondrial metabolism in cardiomyocytes under I/R. Moreover, disrupted mitochondrial homeostasis in I/R myocardium was restored by CHK1 through the promotion of mitochondrial biogenesis and mitophagy. Through mass spectrometry analysis following co-immunoprecipitation, SIRT1 was identified as a direct target of CHK1. The 266–390 domain of CHK1 interacted with the 160–583 domain of SIRT1. Importantly, CHK1 phosphorylated SIRT1 at Thr530 residue, thereby inhibiting SMURF2-mediated degradation of SIRT1. The role of CHK1 in maintaining mitochondrial dynamics control and myocardial protection is abolished by SIRT1 inhibition, while inactivated mutation of SIRT1 Thr530 fails to reverse the impaired mitochondrial dynamics following CHK1 knockdown. CHK1 Δ390 amino acids (aa) mutant functioned similarly to full-length CHK1 in scavenging ROS and maintaining mitochondrial dynamics. Consistently, cardiac-specific SIRT1 knockdown attenuated the protective role of CHK1 in I/R injury. Our findings revealed that CHK1 mitigates I/R injury and restores mitochondrial dynamics in cardiomyocytes through a SIRT1-dependent mechanism. Schematic representation of how CHK1 maintains mitochondrial homeostasis in cardiomyocytes and attenuates myocardial I/R injury through activating SIRT1 signaling. [Display omitted] • Level of CHK1 is downregulated in mice ischemia-reperfusion myocardium. • CHK1 maintains mitochondrial morphology and metabolic homeostasis of cardiomyocytes to alleviate myocardial injury. • Mitochondrial biogenesis and mitophagy are coordinated by CHK1-SIRT1 interaction. • CHK1 phosphorylates SIRT1 at Thr530 residue, thereby inhibiting degradation of SIRT1 in a SMURF2 dependent manner. [ABSTRACT FROM AUTHOR]