Protective effects of Pt-N-C single-atom nanozymes against myocardial ischemia-reperfusion injury
Ontology highlight
ABSTRACT:
SUBMITTER: Ye T
PROVIDER: S-EPMC10891101 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Effective therapeutic strategies for myocardial ischemia/reperfusion (I/R) injury are still lacking. Targeting reactive oxygen species (ROS), the major cause of I/R injury, provides a practical approach to alleviate myocardial damage after reperfusion procedure. Herein, we synthesized an innovative antioxidant nanozyme equipped with single-platinum-atom (PtsaN-C) for protecting against I/R injury. PtsaN-C exhibited potent multiple enzyme-mimicking activities with high-efficiency ROS-scavenging. Mechanistic studies demonstrated that excellent ROS-elimination performance in single platinum atom center was prior to that of platinum cluster center attributing to good synergistic effect and metallic electronic property with nitrogen-doping coordination structure. Systematic in vitro and in vivo studies confirmed that PtsaN-C counteracted ROS efficiently to restore cellular homeostasis and prevented apoptotic progress after I/R injury. PtsaN-C presented excellent biocompatibility and biosafety, making it promising for future clinical application. Current study broadens the horizon of single-atom nanomedicine against ROS-induced damage, offering a promising therapeutic avenue for treatment of I/R injury.
2024-01-16 | PXD048584 |
Project description:BackgroundOur previous studies suggested that deoxyschizandrin (DSD) and schisantherin A (STA) may have cardioprotective effects, but information in this regard is lacking. Therefore, we explored the protective role of DSD and STA in myocardial ischemia-reperfusion (I/R) injury.Methodology/principal findingsAnesthetized male rats were treated once with DSD and STA (each 40 µmol/kg) through the tail vein after 45 min of ischemia, followed by 2-h reperfusion. Cardiac function, infarct size, biochemical markers, histopathology and apoptosis were measured and mRNA expression of gp91 (phox) in myocardial tissue assessed by RT-PCR. Neonatal rat cardiomyocytes were pretreated with DSD and STA and then damaged by H2O2. Cell apoptosis was tested by a flow cytometric assay. Compared with the I/R group: (i) DSD and STA could significantly reduce the abnormalities of LVSP, LVEDP, ±dp/dtmax and arrhythmias, thereby showing their protective roles in cardiac function; (ii) DSD and STA could significantly attenuate the infarct size and MDA release while increasing SOD activity, suggesting a role in reducing myocardial injury; (iii) tissue morphology and myocardial textual analysis revealed that DSD and STA mitigated changes in myocardial histopathology; (iv) DSD and STA decreased apoptosis (33.56±2.58% to 10.28±2.80% and 10.98±1.99%, respectively) and caspase-3 activity in the myocardium (0.62±0.02 OD/mg to 0.38±0.02 OD/mg and 0.32±0.02 OD/mg, respectively), showing their protective effects upon cardiomyocytes; and (v) DSD and STA had similar protective effects on I/R injury as those seen with the positive control metoprolol. In vitro, DSD and STA could significantly decrease the apoptosis of neonatal cardiomyocytes.Conclusions/significanceThese data suggest that DSD and STA can protect against myocardial I/R injury. The underlining mechanism may be related to their role in inhibiting cardiomyocyte apoptosis.
| S-EPMC3631228 | biostudies-literature
Project description:Timely restoration of blood supply following myocardial infarction is critical to save the infarcted myocardium, while reperfusion would cause additional damage. Strontium ions have been shown to promote angiogenesis, but it is unknown whether they can save the damaged myocardium. We report that myocardial ischemia/reperfusion (I/R)-induced functional deterioration and scar formation were notably attenuated by injection of strontium ion-containing composite hydrogels into murine infarcted myocardium at 20 minutes of reperfusion following 60 minutes of ischemia. These beneficial effects were accompanied by reduced cardiomyocyte apoptosis and increased angiogenesis. The effects of strontium ions were further confirmed by the enhanced viability of cardiomyocytes and stimulated angiogenesis in vitro. These findings are the first to reveal the cardioprotective effects of strontium ions against I/R injury, which may provide a new therapeutic approach to ischemic heart disease at a lower cost, with higher stability, and with potentially greater safety.
| S-EPMC7810382 | biostudies-literature
Project description:Thrombotic occlusion of the coronary artery is a key component in the pathogenesis of myocardial ischemia and myocardial infarction (MI). The standard therapy for ischemia is revascularization and restoration of blood flow to previously ischemic myocardium. Paradoxically, reperfusion may result in further tissue damage called ischemia/reperfusion injury (IRI). Platelets play a major role in the pathogenesis of MI and IRI, since they contribute to the thrombus and microthrombi formation, inflammation, release of immunomodulatory mediators, and vasoconstrictive molecules. Antiplatelet therapies have proven efficacy in the prevention of thrombosis and play a protective role in cardiac IRI. Beyond the deterioration effect of platelets in MI and IRI, in the 90s the first reports on a protective effect of molecules released from platelets during MI appeared. However, the role of platelets in cardioprotection is still poorly understood. This review describes the involvement of platelets in MI, IRI, and inflammation. It mainly focuses on the protective role of platelets in MI and IRI. Platelets are involved in cardioprotection based on platelet-releasing molecules and antiplatelet therapy, apart from antiaggregatory effects. Additionally, the use of platelet-derived microparticles as possible markers of MI, with and without comorbidities, and their role in cardioprotection are discussed. This review is aimed at illustrating the present knowledge on the role of platelets in MI and IRI, especially in a context of cardioprotection.
| S-EPMC8169247 | biostudies-literature
Project description:Regulated necrosis (necroptosis) and apoptosis are important biological features of ischemia-reperfusion (I/R) injury. However, the molecular mechanisms underlying myocardial necroptosis remain elusive. Leucine rich repeat containing G protein-coupled receptor 6 (LGR6) has been reported to play important roles in various cardiovascular disease. In this study, we aimed to determine whether LGR6 suppresses I/R-induced myocardial necroptosis and the underlying molecular mechanisms. We generated LGR6 knockout mice and used ligation of left anterior descending coronary artery to produce an in vivo I/R model. The effects of LGR6 and its downstream molecules were subsequently identified using RNA sequencing and CHIP assays. We observed significantly downregulated LGR6 expression in hearts post myocardial I/R and cardiomyocytes post hypoxia and reoxygenation (HR). LGR6 deficiency promoted and LGR6 overexpression inhibited necroptosis and acute myocardial injury after I/R. Mechanistically, in vivo and in vitro experiments suggest that LGR6 regulates the expression of STAT2 and ZBP1 by activating the Wnt signaling pathway, thereby inhibiting cardiomyocyte necroptosis after HR. Inhibiting STAT2 and ZBP1 effectively alleviated the aggravating effect of LGR6 deficiency on myocardial necroptosis after I/R. Furthermore, activating LGR6 with RSPO3 also effectively protected mice from acute myocardial I/R injury. Our findings reveal that RSPO3-LGR6 axis downregulates the expression of STAT2 and ZBP1 through the Wnt signaling pathway, thereby inhibiting I/R-induced myocardial injury and necroptosis. Targeting the RSPO3-LGR6 axis may be a potential therapeutic strategy to treat myocardial I/R injury.
| S-EPMC11550357 | biostudies-literature
Project description:BackgroundCathelicidins are a major group of natural antimicrobial peptides which play essential roles in regulating host defense and immunity. In addition to the antimicrobial and immunomodulatory activities, recent studies have reported the involvement of cathelicidins in cardiovascular diseases by regulating inflammatory response and microvascular dysfunction. However, the role of cathelicidins in myocardial apoptosis upon cardiac ischemia/reperfusion (I/R) injury remains largely unknown.MethodsCRAMP (cathelicidin-related antimicrobial peptide) levels were measured in the heart and serum from I/R mice and in neonatal mouse cardiomyocytes treated with oxygen glucose deprivation/reperfusion (OGDR). Human serum cathelicidin antimicrobial peptide (LL-37) levels were measured in myocardial infarction (MI) patients. The role of CRAMP in myocardial apoptosis upon I/R injury was investigated in mice injected with the CRAMP peptide and in CRAMP knockout (KO) mice, as well as in OGDR-treated cardiomyocytes.ResultsWe observed reduced CRAMP level in both heart and serum samples from I/R mice and in OGDR-treated cardiomyocytes, as well as reduced LL-37 level in MI patients. Knockdown of CRAMP enhanced cardiomyocyte apoptosis, and CRAMP KO mice displayed increased infarct size and myocardial apoptosis. In contrast, the CRAMP peptide reduced cardiomyocyte apoptosis and I/R injury. The CRAMP peptide inhibited cardiomyocyte apoptosis by activation of Akt and ERK1/2 and phosphorylation and nuclear export of FoxO3a. c-Jun was identified as a negative regulator of the CRAMP gene. Moreover, lower level of serum LL-37/neutrophil ratio was associated with readmission and/or death in MI patients during 1-year follow-up.ConclusionsCRAMP protects against cardiomyocyte apoptosis and cardiac I/R injury via activation of Akt and ERK and phosphorylation and nuclear export of FoxO3a. Increasing LL-37 might be a novel therapy for cardiac ischemic injury.
| S-EPMC6381635 | biostudies-literature
Project description:BackgroundSalvianolic acid B is the most abundant water-soluble component in the traditional Chinese medicine Danshen and can reduce myocardial ischemia-reperfusion (MI/R) injury through multiple targets and pathways. However, the role of SalB in protecting the myocardium from ischemia/reperfusion injury remains unclear.PurposeTo perform a preclinical systematic review and meta-analysis to assess the efficacy of Sal B in an animal model of myocardial infarction/reperfusion (MI/R) and to summarize the potential mechanisms of Sal B against MI/R.MethodsStudies published from inception to March 2024 were systematically searched in PubMed, Web of Science, Embase, China National Knowledge Infrastructure Wanfang, and VIP databases. The methodological quality was determined using the SYRCLE RoB tool. The R software was used to analyze the data. The potential mechanisms are categorized and summarized.Results32 studies containing 732 animals were included. The results of the meta-analysis showed that Sal B reduced myocardial infarct size (p < 0.01), and the cardiological indices of CK-MB (p < 0.01), CK (p < 0.01), LDH (p < 0.01), and cTnI (p < 0.01) compared to the control group. In addition, Sal B increased cardiac function indices, such as LVFS (p < 0.01), -dp/dt max (p < 0.01), +dp/dt max (p < 0.01), and cardiac output (p < 0.01). The protective effects of Sal B on the myocardium after I/R may be mediated by attenuating oxidative stress and inflammation, promoting neovascularization, regulating vascular function, and attenuating cardiac myocyte apoptosis. Publication bias was observed in all the included studies. Further studies are required to elucidate the extent of the cardioprotective effects of SalB and the safety of its use.ConclusionTo the best of our knowledge, this is the first meta-analysis of Sal B in the treatment of MI/R injury, and Sal B demonstrated a positive effect on MI/R injury through the modulation of key pathological indicators and multiple signaling pathways. Further studies are needed to elucidate the extent to which SalB exerts its cardioprotective effects and the safety of its use.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/.
| S-EPMC11422085 | biostudies-literature
Project description:Interruption of blood supply to the heart is a leading cause of death and disability. However, the molecular events that occur during heart ischemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a post-translational modification that has been strongly implicated in the protection of cells against a variety of stressors, including ischemia-reperfusion. In particular, the SUMO2/3-specific protease SENP3 has emerged as an important determinant of cell survival after ischemic infarct. Here, we used the Langendorff perfusion model to examine changes in the levels and localisation of SUMOylated target proteins and SENP3 in whole heart. We observed a 50% loss of SENP3 from the cytosolic fraction of hearts after preconditioning, a 90% loss after ischemia and an 80% loss after ischemia-reperfusion. To examine these effects further, we performed ischemia and ischemia-reperfusion experiments in the cardiomyocyte H9C2 cell line. Similar to whole hearts, ischemia induced a decrease in cytosolic SENP3. Furthermore, shRNA-mediated knockdown of SENP3 led to an increase in the rate of cell death upon reperfusion. Together, our results indicate that cardiac ischemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischemia-reperfusion in heart.
| S-EPMC6459529 | biostudies-literature
Project description:Conventional nanozyme technologies face formidable challenges of intricate size-, composition-, and facet-dependent catalysis and inherently low active site density. We discovered a new class of single-atom nanozymes with atomically dispersed enzyme-like active sites in nanomaterials, which significantly enhanced catalytic performance, and uncovered the underlying mechanism. With oxidase catalysis as a model reaction, experimental studies and theoretical calculations revealed that single-atom nanozymes with carbon nanoframe-confined FeN5 active centers (FeN5 SA/CNF) catalytically behaved like the axial ligand-coordinated heme of cytochrome P450. The definite active moieties and crucial synergistic effects endow FeN5 SA/CNF with a clear electron push-effect mechanism, as well as the highest oxidase-like activity among other nanozymes (the rate constant is 70 times higher than that of commercial Pt/C) and versatile antibacterial applications. These suggest that the single-atom nanozymes have great potential to become the next-generation nanozymes.
| S-EPMC6499548 | biostudies-literature
Project description:Ischemic stroke is one of the most common causes of mortality worldwide and is a primary cause of disability and mortality in adults. There is an unmet need for drugs that can effectively treat ischemic stroke. Hence, the present study explored the neuroprotective effects of andrographolide (Andro) in a mouse model of bilateral common carotid artery occlusion, and systematically evaluated the potential mechanisms underlying its effects. The effects of Andro on mouse brain tissue following cerebral ischemia‑reperfusion injury (CIRI) were evaluated by histopathological (H&E and Nissl) and immunofluorescence [glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN)] staining. A traditional Chinese medicine‑based network pharmacology method was performed to establish and analyze compound‑target‑disease and function‑pathway networks in order to elucidate the possible mechanisms responsible for the protective role of Andrographis paniculata in CIRI. In addition, western blot analysis and RT‑qPCR was performed to evaluate the expression and activation of signaling proteins predicted to be involved in this mechanism. The amelioration of histopathological alterations was observed in mice pre‑treated with Andro. Immunofluorescence staining revealed that Andro decreased the expression of GFAP and increased the expression of NeuN, and significantly decreased the levels of pro‑inflammatory cytokines (IL‑1β, IL‑6 and TNF‑α). Network pharmacology analysis revealed that neuroinflammatory response and apoptosis were associated with the effects of Andrographis paniculata on CIRI. Western blot analysis revealed that the mice pre‑treated with Andro exhibited an upregulated protein expression of tropomyosin receptor kinase B (TrkB), p‑PI3K and p‑Akt, as well as a decrease in the expression of GFAP and an increase in the expression of NeuN. In addition, the data of RT‑qPCR indicated that the mice pre‑treated with Andro exhibited a significantly decreased expression of encoding IL‑1β mRNA, IL‑6 mRNA and TNF‑α mRNA in the brain compared to the untreated mice following CIRI. On the whole, the findings of the present study suggest that pre‑treatment with Andro exerts a protective effect against CIRI, which may be partly related to its potential to reduce neuroinflammatory response and apoptosis in patients with stroke.
| S-EPMC8416143 | biostudies-literature