Myocardial Ischemia-reperfusion Injury Research Articles

MiRNA-541-5p regulates myocardial ischemia–reperfusion injury by targeting ferroptosis

BackgroundThis article aims to use high-throughput sequencing to identify miRNAs associated with ferroptosis in myocardial ischemia–reperfusion injury, select a target miRNA, and investigate its role in H9C2 cells hypoxia-reoxygenation injury.MethodsSD rats and H9C2 cells were used as subjects. ELISA kits quantified MDA, SOD, GSH, LDH, and ferritin levels. TTC staining evaluated infarction size. HE staining observed histopathological changes. DCFH-DA fluorescent probe detected ROS. CCK-8 kit measured cell viability. HiSeq 2000 sequencing performed differential expression analysis of miRNAs. qRT-PCR and Western blots assessed the expression levels of GPX-4, ACSL-4, HO-1, TFR-1 and TFR-2. SPSS 21.0 software conducted statistical analysis.ResultsMyocardial ischemia–reperfusion injury resulted in decreased levels of SOD and GSH, increased levels of LDH and MDA, up-regulation of ferritin, ACSL-4, HO-1, and TFR-2, down-regulation of GPX-4, increased tissue damage, and accumulation of ROS. However, DFO treatment reversed these changes. Subsequently, the target gene miRNA-541-5p was obtained by miRNA sequencing screening, and further validation revealed that miRNA-541-5p expression was increased in the myocardial tissues of rats in the I/R injury model group compared with those of rats in the NC group, P < 0.05. Subsequently, by constructing H9C2 cell lines with miRNA-541-5p overexpression and miRNA-541-5p expression inhibition, miRNA-541-5p expression was inversely correlated with the survival of H9C2 cells after hypoxia-reoxygenation injury. miRNA-541-5p up-regulation led to a decrease in SOD and GSH, an increase in ferritin and MDA, and an accumulation of ROS. wb and qRT-PCT demonstrated that high miRNA-541-5p expression up-regulated the expression of protein/mRNA expression of ACSL-4, HO-1, ferritin, and TFR-1, but down-regulated protein/mRNA expression of GPX-4. In addition, ADAM 7, FNIP 2, HOXD 10, HCCS and STK 3 were preliminarily identified as potential candidate target genes for miRNA-541-5p by bioinformatics analysis. Among them, ADAM7 emerges as the most suitable potential target gene based on the selection criteria.ConclusionIn summary, miRNA-541-5p may be a biomarker of myocardial I/R damage diseases and can regulate oxidative stress and iron death by inhibiting the expression of miRNA-541-5p, thereby reducing mechanisms of I/R injury.

Evidence and perspectives on miRNA, circRNA, and lncRNA in myocardial ischemia-reperfusion injury: a bibliometric study

Evidence and perspectives on miRNA, circRNA, and lncRNA in myocardial ischemia-reperfusion injury: a bibliometric study

Ferroptosis and its relationship with cancer

Marked by iron buildup and lipid peroxidation, ferroptosis is a relatively new regulatory cell death (RCD) pathway. Many diseases like cancer, myocardial ischemia-reperfusion injury (MIRI), neurological disorders and acute renal failure (AKI) are corelated with ferroptosis. The main molecular processes of ferroptosis discovered yet will be presented here, along with the approaches in which it interacts with tumour-associated signaling pathways and its uses in systemic therapy, radiation therapy, and immunotherapy managing tumors.

Mechanism of Qilong Capsule against Myocardial Ischemia-Reperfusion Injury Based on Network Pharmacology and Experimental Validation.

Qilong capsule (QC) has been used clinically to treat ischemic stroke in China. This study evaluated the therapeutic effects of QC on myocardial ischemia-reperfusion injury (MIRI) and its potential mechanisms. The components and candidate targets of QC against MIRI were predicted by network pharmacology via relevant databases such as TCMSP, BATMAN-TCM, GeneCards. The potential mechanisms were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and verified by enzyme-linked immunosorbent assay (ELISA) and Western blot. Network pharmacology analysis indicated that the cardioprotective effect of QC against MIRI was associated with inflammatory pathways. We further confirmed that QC effectively decreased the levels of inflammatory factors, including hs-CRP and MCP-1, and suppressed the expression of TNF-α and the phosphorylation of STAT3. This study provides evidence for further clinical applications of QC for MIRI therapy.

Notoginsenoside R1 Attenuates H/R Injury in H9c2 Cells by Maintaining Mitochondrial Homeostasis

Mitochondrial homeostasis is crucial for maintaining cellular energy production and preventing oxidative stress, which is essential for overall cellular function and longevity. Mitochondrial damage and dysfunction often occur concomitantly in myocardial ischemia–reperfusion injury (MIRI). Notoginsenoside R1 (NGR1), a unique saponin from the traditional Chinese medicine Panax notoginseng, has been shown to alleviate MIRI in previous studies, though its precise mechanism remains unclear. This study aimed to elucidate the mechanisms of NGR1 in maintaining mitochondrial homeostasis in hypoxia/reoxygenation (H/R) H9c2 cells. The results showed that NGR1 pretreatment effectively increased cell survival rates post-H/R, reduced lactate dehydrogenase (LDH) leakage, and mitigated cell damage. Further investigation into mitochondria revealed that NGR1 alleviated mitochondrial structural damage, improved mitochondrial membrane permeability transition pore (mPTP) persistence, and prevented mitochondrial membrane potential (Δψm) depolarization. Additionally, NGR1 pretreatment enhanced ATP levels, increased the activity of mitochondrial respiratory chain complexes I–V after H/R, and reduced excessive mitochondrial reactive oxygen species (mitoROS) production, thereby protecting mitochondrial function. Further analysis indicated that NGR1 upregulated the expression of mitochondrial biogenesis-related proteins (PGC-1α, Nrf1, Nrf2) and mitochondrial fusion proteins (Opa1, Mfn1, Mfn2), while downregulating mitochondrial fission proteins (Fis1, Drp1) and reducing mitochondrial autophagy (mitophagy) levels, as well as the expression of mitophagy-related proteins (Pink1, Parkin, BNIP3) post-H/R. Therefore, this study showed that NGR1 can maintain mitochondrial homeostasis by regulating mitophagy, mitochondrial fission–fusion dynamics, and mitochondrial biogenesis, thereby alleviating H9c2 cell H/R injury and protecting cardiomyocytes.

Mangiferin Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the GAS6/Axl Signaling Pathway.

Ischemia reperfusion-induced myocardial injury is a prominent pathological feature in patients with coronary artery disease, contributing to significant mortality and morbidity rates. Mangiferin (MGF), the main active ingredient extracted from Anemarrhena asphodeloides Bge, has anti-inflammatory, anti-oxidation, anti-diabetes, and anti-tumor effects. The present study confirmed that the GAS6/Axl pathway was identified as a promising novel target for the treatment of myocardial ischemia reperfusion (IR) injury. However, whether MGF exerts anti-myocardial ischemia reperfusion injury through GAS6/Axl is still unclear. In this study, BALB/c male mice and HL-1 cardiomyocytes were used to construct a model of IR and hypoxia-reoxygenation (HR) (or H2O2) injury invivo and invitro, respectively. MGF significantly improved cardiac function indicators, myocardial structure, myocardial enzymes, and mitochondrial function, together with reduced oxidative stress and apoptosis in IR-injured mice. Invitro, MGF significantly increased cell viability, inhibited the release of LDH, reduced oxidative stress and apoptosis, and improved mitochondrial function in both HR and H2O2-injured HL-1 cells. In particular, the GAS6/Axl signaling pathway plays an important role in this process. Additionally, we also demonstrated that GAS6 gene knockout reversed the protective effect of MGF against HR and H2O2-injured cardiomyocytes. The present study confirmed that MGF has protective effects against myocardial IR injury by activating the GAS6/Axl pathway, providing a theoretical basis for MGF as a potential cardioprotective drug in the clinical setting of myocardial IR injury.

Protective mechanism of safflower yellow injection on myocardial ischemia-reperfusion injury in rats by activating NLRP3 inflammasome

ObjectivesThis study intended to explore whether the protective effect safflower yellow injection (SYI) on myocardial ischemia-reperfusion (I/R) injury in rats mediated of the NLRP3 inflammasome signaling.MethodsThe I/R model was prepared by ligating the left anterior descending coronary artery for 45 min and then releasing the blood flow for 150 min. 96 male Wistar rats were randomly divided into sham group, I/R group, Hebeishuang group (HBS), SYI high-dose group (I/R + SYI-H), SYI medium-dose group (I/R + SYI-M) and SYI low-dose group (I/R + SYI-L). Cell experiments were divided into normal control group (NC), Oxygen glucose deprivation/reoxygenation group (OGD/R), OGD/R + SYI group, OGD/R + SYI + Chloroquine group (OGD/R + SYI + CQ). The area of myocardial ischemia infarction and pathological changes were observed by the Tetrazolium method (TTC) and HE staining. Myocardial enzymes such as aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) were measured by chemiluminescence (CL) method. The inflammatory factors levels of TNF-α, IL-1β, MCP-1, and IL-6 were detected by ELISA. The expressions of inflammatory-related proteins (Caspase-1, NLRP3, TLR4, NF-κB), autophagosome-related proteins (LC3-I, LC3-II,LC3-II/LC3-I), apoptosis-related proteins (Bax, Bcl-2, Caspase-3, Bcl-2/Bax) and autophagy-related proteins (p62/SQSTM1, PI3K, p-Akt, mTOR) were detected by Western-Blot. Cell morphology and cell viability were detected by transmission electron microscopy and CCK-8.ResultsIn vivo, compared with sham group, the percentage of myocardial infarction area was increased and myocardial tissue arrangement was disordered in I/R group. In addition, the activities of myocardial enzymes, the contents of inflammatory factors, the expressions of inflammatory-related proteins, autophagy-related proteins, autophagosome-related proteins, Bax and Caspase-3 were increased, while Bcl-2 and Bcl-2/Bax were decreased. SYI treatment reversed these trends, except for the expression of autophagosome-related proteins. In vitro, SYI decreased the contents of inflammatory factors and the expressions of inflammatory-related proteins, autophagy-related proteins and autophagosome-related proteins caused by OGD/R. However, the contents of inflammatory factors and the expression of inflammatory-related proteins, p62/SQSTM1 and mTOR were increased, while PI3K, p-AKT, LC3-II/LC3-I were significantly decreased in OGD/R + SYI + CQ group.ConclusionsSYI can promote myocardial tissue autophagy by regulating NLRP3, thereby attenuating the myocardial inflammatory response and protecting damaged myocardium in I/R rats.

Arachidonic acid synergizes with aspirin preventing myocardial ischemia-reperfusion injury and mitigates bleeding risk.

The therapeutic efficacy of coronary revascularization is compromised by myocardial ischemia-reperfusion (MI/R) injury. Higher levels of circulating arachidonic acid (AA) are reportedly associated with lower risk of cardiovascular disease. The cyclooxygenase (COX) pathway metabolizes AA into prostaglandins (PGs) and the platelet-activating thromboxane A2 (TXA2), which is inhibited by aspirin. We aimed to explore whether AA or its combination with aspirin modulates MI/R injury and aspirin-caused gastric bleeding. Mice were subjected to 30min coronary artery ligation followed by reperfusion. AA reduced MI/R injury in mice, and its combination with aspirin provided further cardioprotection. Aspirin inhibited MI/R-triggered platelet activation and ameliorated microvascular obstruction immediately upon reperfusion, whereas AA improved microvascular perfusion at a later stage of reperfusion, coinciding with increased coronary vasodilatation. Co-administration of AA and aspirin markedly reduced cardiac neutrophil infiltration and vascular permeability and improved microcirculation. AA increased urinary metabolites of PGI2 and PGE2, not TXA2, and this selective augmentation was further enhanced by co-treatment with aspirin. Elevation in PGI2 and PGE2 correlated with reduced infarction and improved ventricular function, and inhibiting COX-2 attenuated the synergistic cadioprotection. Furthermore, oral administration of AA with aspirin after reperfusion provided a maximal cardioprotection and abolished aspirin-caused gastric bleeding. AA synergizes with aspirin in protecting against MI/R injury, while minimizing the related bleeding risk, a major concern for patients with acute myocardial infarction. This is attributable to the selective augmentation of PGI2 and PGE2 that is amplified by TXA2 suppression by aspirin, underscoring improved microcirculation and ameliorated inflammation.

Lidocaine Alleviates Myocardial Ischemia-Reperfusion Injury in Rats through JNK Signaling Pathway

Lidocaine Alleviates Myocardial Ischemia-Reperfusion Injury in Rats through JNK Signaling Pathway

Novel Selective Cardiac Myosin-Targeted Inhibitors Alleviate Myocardial Ischaemia–Reperfusion Injury

Abstract Purpose Reperfusion of the ischaemic heart is essential to limit myocardial infarction. However, reperfusion can cause cardiomyocyte hypercontracture. Recently, cardiac myosin-targeted inhibitors (CMIs), such as Mavacamten (MYK-461) and Aficamten (CK-274), have been developed to treat patients with cardiac hypercontractility. These CMIs are well tolerated and safe in clinical trials. We hypothesised that, by limiting hypercontraction, CMIs may reduce hypercontracture and protect hearts in the setting of ischaemia and reperfusion (IR). Methods We investigated the ability of MYK-461 and CK-274 to inhibit hypercontracture of adult rat cardiomyocytes (ARVC) in vitro following ATP depletion. A suitable dose of CMIs for subsequent in vivo IR studies was identified using cardiac echocardiography of healthy male Sprague Dawley rats. Rats were anaesthetized and subject to coronary artery ligation for 30 min followed by 2 h of reperfusion. Prior to reperfusion, CMI or vehicle was administered intraperitoneally. Ischaemic preconditioning (IPC) was used as a positive control group. Infarct size was assessed by tetrazolium chloride staining and extent of hypercontracture was assessed by histological staining. Results Treatment with CMIs inhibited ARVC hypercontracture in vitro. MYK-461 (2 mg/kg) and CK-274 (0.5 mg/kg to 2 mg/kg) significantly reduced infarct size vs. vehicle. IR caused extensive contraction band necrosis, which was reduced significantly by IPC but not by CMIs, likely due to assay limitations. GDC-0326, an inhibitor of PI3Kα, abrogated CK-274-mediated protection following IR injury. GDC-0326 reduced phosphorylation of AKT when administered together with CK-274. Conclusion This study identifies CMIs as novel cardioprotective agents in the setting of IR injury.

Inhibition of CCR2 attenuates NLRP3-dependent pyroptosis after myocardial ischaemia-reperfusion in rats via the NF-kB pathway.

Myocardial infarction (MI) is a leading cause of mortality worldwide, contributing significantly to long-term cardiac dysfunction and heart failure. Effective therapeutic strategies are urgently needed to mitigate the extensive damage caused by MI and subsequent ischemia-reperfusion (I/R) injury. This study investigates the role of the Chemokine receptor 2 (CCR2) in regulating NLRP3-dependent cardiomyocyte pyroptosis following myocardial ischemia-reperfusion (MIR), elucidating its molecular mechanisms. A myocardial ischemia-reperfusion model was established using 124 Sprague-Dawley rats by ligating the left coronary artery, inducing 30min of ischemia. Following ischemia, RS504393, a selective CCR2 antagonist, was administered intraperitoneally one hour after reperfusion. To further explore the underlying mechanisms, the NF-κB pathway agonist Phorbol 12-myristate 13-acetate (PMA) was administered 1h post-MIR. The results showed a marked increase in CCR2 expression in the heart, peaking on the first day of reperfusion. Treatment with RS504393 significantly improved short-term cardiac function and reduced myocardial infarction size, decreased myocardial pyroptosis and suppressed the expression of NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18 through inhibition of the NF-κB signaling pathway. This effect was reversed with the administration of PMA. In summary, the inhibition of CCR2 shows potential in mitigating myocardial injury following MIR by modulating the NF-κB signaling pathway. These findings highlight CCR2 as a promising therapeutic target for myocardial ischemia-reperfusion injury.

MMP-2 inhibition attenuates ER stress-mediated cell death during myocardial ischemia-reperfusion injury by preserving IRE1α

Endoplasmic reticulum (ER) stress is one of the major events accompanying myocardial ischemia-reperfusion (IR) injury, as hypoxia and oxidative stress disrupt protein folding in the ER. As a result, the unfolded protein response (UPR) is activated through different sensors including inositol-requiring enzyme 1α (IRE1α) and protein kinase R-like ER kinase (PERK). Failure of the UPR to reduce ER stress induces cellular dysfunction. Matrix metalloproteinase-2 (MMP-2) is a ubiquitous protease that is activated intracellularly in response to oxidative stress and partially localizes near the ER. However, its role in ER homeostasis is unknown. We hypothesized that MMP-2 is involved in the regulation of the UPR and ER stress-mediated apoptosis during IR injury. Isolated mouse hearts subjected to IR injury showed impaired recovery of post-ischemic contractile function compared to aerobically perfused controls. Ventricular extracts from IR hearts had higher levels of glucose-regulated protein-78 and protein disulfide isomerase and lower levels of IRE1α and PERK compared to aerobic controls. MMP-2 inhibitors, ARP-100 or ONO-4817, given 10 min before ischemia, improved cardiac post-ischemic recovery and preserved IRE1α level in hearts subjected to 30 min ischemia/40 min reperfusion. IR also increased the levels of CHOP and mitochondrial Bax and caspase-3 and -9 activities, indicating induction of apoptosis, all of which were attenuated by MMP-2 inhibitors, regardless of the reperfusion time. Immunoprecipitation showed an association between MMP-2 and IRE1α in aerobic and IR hearts. During myocardial IR injury MMP-2 may impair the UPR and induce apoptosis by proteolysis of IRE1α. Inhibition of MMP-2 activity protects against cardiac contractile dysfunction in part by preserving IRE1α and preventing the progression to myocardial cell death.

Paeoniflorin ameliorates reperfusion injury in H9C2 cells through SIRT1-PINK1/parkin-mediated mitochondrial autophagy.

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.

Dihydrotanshinone I improves cardiac function by promoting lymphangiogenesis after myocardial ischemia-reperfusion injury.

Dihydrotanshinone I (DHT) is an active ingredient derived from Salvia miltiorrhiza. Previous studies have demonstrated that DHT can improve cardiac function in rats with myocardial ischemia-reperfusion injury (IR). However, the mechanism by which DHT improves myocardial injury in rats still requires further research. Lymphangiogenesis can reduce myocardial edema, inflammation, and fibrosis after myocardial infarction in rats, and improve cardiac function. In this study, the changes in cardiac functions, collagen fiber deposition in the infarcted area and the level of relevant indicators of lymphangiogenesis were examined by echocardiography, Masson's trichrome staining, immunohistochemistry and Western blot, respectively. Human lymphatic endothelial cells (HLECs) were transfected with siVE-cadherin and siVEGFR-3, and the effects of DHT on HLEC cell viability, migration and tube formation were detected through CCK8, TUNEL, transwell, wound healing and tube formation assay. We found that in myocardial IR rats treated with DHT, the levels of LYVE-1, PROX1, VEGF-C, VEGFR-3, IGF-1, podoplanin and IGF-1R, which are associated with lymphangiogenesis, were increased, as well as the level of VE-cadherin, which maintains endothelial cell function. DHT reduced the levels of inflammatory factors and myocardial cell apoptosis, thereby improving cardiac function after I/R. To explore the mechanism of DHT promoting lymphangiogenesis, H2O2 and OGD/R injury models of HLECs were constructed to simulate the microenvironment of myocardial IR in vitro. The results proved that DHT could reduce the damage and apoptosis of HLECs. On the other hand, DHT enhanced the expression of VEGFR-3 and VE-cadherin in HLECs, promoted cell migration and tube formation. The effects of DHT on the tube formation and migration of HLECs were significantly decreased after knocking down VEGFR-3 or VE-cadherin. Our research proposed that DHT could improve the heart function after IR through the enhancement of lymphangiogenesis and contributed to the development of the treatment methods for myocardial IR.

Progress in Chinese medicine monomers and their nanoformulations on myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion injury (MIRI) is the entire process of myocardial injury resulting from ischemia and hypoxia following acute myocardial infarction, which involves complicated pathogenesis including energy metabolism disorders, calcium overload, oxidative stress and mitochondrial dysfunction. Traditional Chinese medicine (TCM) has attracted intensive attention in the treatment of MIRI owing to its multitarget therapeutic effects and low systemic toxicity. Increasing evidence indicates the promising application of TCM on the protection of cardiomyocytes, improvement of endothelial cell functions and regulation of energy metabolism and inflammatory response. Although the efficacy of TCM has been well-proven, the underlying mechanisms remain unclear. Additionally, the clinical application of much TCM had been hampered due to its low aqueous solubility, poor gastrointestinal absorption, and decreased bioavailability. In this review, we examined the pathological mechanism of MIRI and highlighted recent research studies on the therapeutic effects and molecular mechanisms of monomer compounds derived from TCM. We also summarized the latest studies in nanoformulation-based strategies for improving the targeting and stability of TCM monomers and exerting synergistic effects. The aim of this study was to provide a scientific basis for the treatment of MIRI with TCM monomers combined with nanomaterials, revealing their clinical significance and development prospects.

Innovative engineering of superoxide dismutase for enhanced cardioprotective biocatalysis in myocardial ischemia-reperfusion injury

The present research compares the stability, catalytic activity, and cardioprotective benefits of the designed superoxide dismutase (SOD) variation SOD-M3 to those of the naturally occurring enzyme, along with additional alternatives. SOD-M3 exhibited a 51.5 % increase in expression yield, reaching 50 mg/L, compared to the wild-type's 33 mg/L. In structural biology, the average distance between atoms of stacked proteins or molecules is measured by RMSD. Testing the precision of protein-ligand docking models is a typical application. The projected structure closely resembles the reference or native structure when the RMSD is low. The enzyme's durability improved significantly, resulting in negligible aggregation in the Size Exclusion Chromatography (SEC) and root mean square deviation (RMSD) of 2.1 Å. SOD-M3 catalytically increased superoxide radical scavenging capability by 40 % and inhibited nitroblue tetrazolium (NBT) reduction by 90 % at 1 μg/mL concentration. The material exhibited increased stability, as seen by its decomposition temperature (Tm) of about 80 °C, as opposed to 65 °C in the wild-type strains. In cardiomyocyte protection experiments, SOD-M3 reduced lactate dehydrogenase (LDH) production by 55 % while decreasing reactive oxygen species (ROS) concentrations by 60 %. Since a 51.5 % increase in expression yield for SOD-M3 indicates improved production efficiency, which makes large-scale manufacturing more viable for clinical applications, it is therapeutically essential. Higher expression yields mean more cost-effective manufacture for enzyme-based therapy research and commercialization. In vivo, SOD-M3 decreased myocardial infarction diameter by 44 % while improving cardiac function, including increased ejection percentage and fractional contraction. The histopathological investigation revealed undamaged heart tissue and less necrotic areas. The results reported here demonstrate SOD-M3's superior activity of enzymes, cardioprotective perspective, and stability, making it a promising therapeutic alternative for illnesses related to cellular oxidation & ischemic cardiac diseases. An increase in enzyme concentrations can enhance the obtaining of reactive oxygen species (ROS), which build up during ischaemia episodes; therefore, this increase is essential. Improving the enzyme's solubility and stability by site-directed modifications makes SOD-M3 more stable and effective in physiological circumstances where its activity is crucial for therapeutic efficacy maximization. A further benefit of increased expression yield is that it can lower manufacturing costs, which will help get SOD-M3 into clinical settings. These modifications raise SOD-M3's cardioprotective potential, making it a strong contender for novel therapies against cardiac ischemia-reperfusion impacts.

Construction of AMPK-related circRNA network in mouse myocardial ischemia–reperfusion injury model

Construction of AMPK-related circRNA network in mouse myocardial ischemia–reperfusion injury model

Molecular and metabolic landscape of adenosine triphosphate-induced cell death in cardiovascular disease.

The maintenance of intracellular and extracellular adenosine triphosphate (ATP) levels plays a pivotal role in cardiac function. In recent years, burgeoning attention has been directed towards ATP-induced cell death (AICD), revealing it as a distinct cellular demise pathway triggered by heightened extracellular ATP concentrations, distinguishing it from other forms of cell death such as apoptosis and necrosis. AICD is increasingly acknowledged as a critical mechanism mediating the pathogenesis and progression of various cardiovascular maladies, encompassing myocardial ischemia-reperfusion injury, sepsis-induced cardiomyopathy, hypertrophic cardiomyopathy, arrhythmia, and diabetic cardiomyopathy. Consequently, a comprehensive understanding of the molecular and metabolic underpinnings of AICD in cardiac tissue holds promise for the prevention and amelioration of cardiovascular diseases. This review first elucidates the vital physiological roles of ATP in the cardiovascular system, subsequently delving into the intricate molecular mechanisms and metabolic signatures governing AICD. Furthermore, it addresses the potential therapeutic targets implicated in mitigating AICD for treating cardiovascular diseases, while also delineating the current constraints and future avenues for these innovative therapeutic targets, thereby furnishing novel insights and strategies for the prevention and management of cardiovascular disorders.

Sevoflurane Alleviates Myocardial Ischemia/Reperfusion Injury by Targeting the circ_CDR1as/miR‐671‐5p/HMGA1 Axis

ABSTRACTSevoflurane (Sev) has a cardioprotective role in myocardial ischemia/reperfusion injury (MI/RI), but its mechanism has not been fully elucidated. This study aimed to investigate whether the circ_CDR1as/miR‐671‐5p/HMGA1 axis mediates the cardioprotective effect of Sev in MI/RI. Cardiomyocytes underwent hypoxia/reoxygenation (H/R) treatment was used to simulate MI/RI in vitro. H/R cardiomyocytes were then pretreated with Sev to explore the protective effect of Sev on H/R cells. The level of CDR1as/miR‐671‐5p/HMGA1 axis were detected by RT‐qPCR. The proliferation and apoptosis of cardiomyocytes were detected by CCK‐8 and flow cytometry. The levels of myocardial injury markers and inflammatory markers were detected by ELISA assay. Finally, the regulatory relationship between CDR1as and miR‐671‐5p/HMGA1 axis was verified by Dual‐luciferase reporting and RNA pull‐down assays. Sev Pretreatment can reduce the level of CDR1as and mitigate H/R‐induced damage to cardiomyocytes. This Pretreatment lowers the levels of myocardial injury markers, oxidative stress markers, and pro‐inflammatory factors in H/R‐affected cardiomyocytes. However, CDR1as overexpression inhibits Sev's protective effect on H/R cardiomyocytes. At the molecular mechanism, we found that CDR1as mediates Sev's protective effect through the CDR1as/miR‐671‐5p/HMGA1 axis. CDR1as increases HMGA1 levels by sponging miR‐671‐5p, while high HMGA1 levels diminish Sev's protective effect. Sev plays a cardioprotective role in MI/RI by inhibiting the circ_CDR1as/miR‐671‐5p/HMGA1 axis.

Mechanistic analysis of Tanshinone IIA's regulation of the ATM/GADD45/ORC signaling pathway to reduce myocardial ischemia-reperfusion injury.

By far, one of the best treatments for myocardial ischemia is reperfusion therapy. The primary liposoluble component of Danshen, a traditional Chinese herbal remedy, Tanshinone ⅡA, has been shown to have cardiac healing properties. The purpose of this work is to investigate the processes by which Tanshinone ⅡA influences myocardial ischemia-reperfusion injury (MIRI) in the H9C2 cardiac myoblast cell line, as well as the association between Tanshinone ⅡA and MIRI. The cardiac cells were divided into a normal group, a model group and Tanshinone ⅡA treatment groups. After 4h of culture with the deprivation of oxygen and glucose, the cells were incubated normally for 2h. The success of the model and the capacity of Tanshinone ⅡA to heal cardiac damage were validated by the outcomes of cell viability, morphology, and proliferation. The efficacy of Tanshinone ⅡA in treating MIRI was further confirmed by the scratch assay and biomarker measurement. The differentially expressed genes were examined using transcriptome sequencing. The Ataxia-Telangiectasia Mutated (ATM)/Growth Arrest and DNA Damage (GADD45)/Origin Recognition Complex (ORC) signaling pathway was identified as being crucial to this process by KEGG pathway analysis and GO enrichment. Molecular docking and RT-qPCR were used to confirm our results. The crucial function of the ATM/GADD45/ORC pathway was further confirmed by the addition of an ATM inhibitor, which inhibited the expression of ATM. Tanshinone ⅡA can relieve the myocardial ischemia-reperfusion injury in cardiac cells by activating the ATM/GADD45/ORC pathway.