Protección miocárdica

Chin Med. 2025 Jun 18;20(1):90. doi: 10.1186/s13020-025-01141-x.

ABSTRACT

INTRODUCTION: Ischemic heart diseases are the leading cause of death worldwide due to the inability of regeneration of adult cardiomyocytes (CMs). Natural products from medical herbs are an important source of innovative drugs for many diseases including cardiovascular diseases.

OBJECTIVES: In this study, we set out to screen novel small-molecule therapies from natural products to protect heart against ischemic injury.

METHODS: High-throughput screening was performed using a natural product library to identify the potential small molecules which can promote survival of CMs under ischemic and ischemic/reperfusion conditions. In addition, myocardial infarction (MI) and ischemia/reperfusion (I/R) mice models were used to evaluate the in vivo effects of the screened candidate. We also applied various analysis including cell viability, qPCR, Western blot, immunofluorescent staining, echocardiography, Masson's staining, TTC staining, and network pharmacology.

RESULTS: High-throughput screening showed that the small molecule compound Darutigenol (Dar), derived from the Chinese traditional herb Herba Siegesbeckiae, could significantly promote CM survival and proliferation under ischemic conditions. Moreover, I/R-induced CM apoptosis and ROS generation could be significantly reduced by Dar treatment. In addition, in vivo administration of Dar was able to attenuate MI- and I/R-induced cardiac injury in adult mice by decreasing fibrosis and apoptosis, thereby improving cardiac function. Network pharmacology analysis and molecule docking assay showed that Dar has the highest binding affinity with AKT1 protein. Western blotting assay further revealed that AKT1 activation was significantly enhanced by Dar administration in the infarcted hearts.

CONCLUSIONS: Our data revealed that the small molecule compound Dar, screened from the natural product library in this study, is capable of protecting heart against MI and I/R injury by activating AKT1 pathway. These findings enrich the natural product candidates for cardiovascular disease treatment and provide new insights into potential therapeutic agents for MI and I/R injury.

PMID:40533778 | PMC:PMC12175470 | DOI:10.1186/s13020-025-01141-x

Atherosclerosis. 2025 Jun 13:120405. doi: 10.1016/j.atherosclerosis.2025.120405. Online ahead of print.

ABSTRACT

Influenza infection is a well-established trigger of acute cardiovascular events, particularly myocardial infarction, mediated by systemic inflammation, endothelial dysfunction, and thrombosis. In this review, we examine the evidence supporting influenza vaccination as a preventive strategy in cardiovascular disease. Observational studies and randomized trials consistently show reduced cardiovascular event rates among vaccinated individuals, with the most pronounced benefit seen after myocardial infarction. Emerging data suggest that the effects of vaccination extend beyond infection prevention, involving immunomodulatory effects, including regulatory T cell activity, features of trained innate immunity, and mechanisms promoting resolution of inflammation. Unlike conventional anti-inflammatory therapies, vaccination appears to rebalance immune responses without compromising host defence. We also consider an evolutionary perspective, proposing that historical influenza exposure may have contributed to the genetic architecture of atherosclerosis. Taken together, current evidence positions influenza vaccination as a safe, low-cost, and biologically plausible intervention in the prevention of cardiovascular events. However, important questions remain. Whether revaccination during hospitalization provides added benefit in previously immunized individuals, and the potential of high-dose or next-generation vaccine platforms such as mRNA, warrant further study. Dedicated outcome trials conducted outside the influenza season are especially needed to clarify nonspecific cardiovascular benefits. Cardiologists and other stakeholders share a responsibility to implement existing guidelines with the same commitment given to statins and platelet inhibitors.

PMID:40533320 | DOI:10.1016/j.atherosclerosis.2025.120405

Int Immunopharmacol. 2025 Jun 17;161:115065. doi: 10.1016/j.intimp.2025.115065. Online ahead of print.

ABSTRACT

Sepsis-induced myocardial dysfunction (SIMD), a life-threatening complication of systemic infection, lacks effective therapies. This study investigated whether Gastrodin (GAS) alleviates SIMD by modulating ubiquitination and histone lactylation pathways. Using an in vivo lipopolysaccharide (LPS)-induced murine model and in vitro TNF-α-stimulated human cardiomyocytes (AC16), we evaluated the effects of GAS on myocardial injury, inflammation, and apoptosis. GAS treatment significantly reduced myocardial damage, serum cardiac injury markers (cTnT, CK-MB), and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in mice. Transcriptomic analysis also enriched for inflammatory and apoptotic pathways. In vitro, GAS protected AC16 cells from TNF-α-induced apoptosis and suppressed glycolysis-derived lactate accumulation. Mechanistically, GAS enhanced CDT2-KAT2A binding, promoting ubiquitin-mediated KAT2A degradation, which reduced histone H3 lysine 14 lactylation (H3K14la) and restored energy metabolism. Multi-omics integration confirmed the role of GAS in glycolytic inhibition and lactylation modulation. These findings demonstrated that GAS ameliorates SIMD by targeting the CDT2-KAT2A axis to regulate ubiquitination-lactylation, providing novel therapeutic insights for septic cardiomyopathy.

PMID:40532326 | DOI:10.1016/j.intimp.2025.115065

J Cardiovasc Med (Hagerstown). 2025 May 22. doi: 10.2459/JCM.0000000000001737. Online ahead of print.

ABSTRACT

BACKGROUND: De-escalation of dual antiplatelet therapy (DAPT) by early discontinuation of one antiplatelet agent has been proposed as an alternative to 12-month DAPT to balance ischemic and bleeding risks in patients with acute coronary syndrome (ACS). However, the efficacy and safety of abbreviated DAPT regimens in ST-elevation myocardial infarction (STEMI) - a subset of ACS with distinct clinical and risk profiles - remain uncertain.

METHODS: Randomized trials and sub-analyses of randomized trials comparing DAPT de-escalation by early discontinuation versus 12-month DAPT in patients with STEMI treated with primary angioplasty were included. Co-primary endpoints were major bleeding and major adverse cardiovascular events (MACE). Secondary endpoints included net adverse clinical events (NACE), individual ischemic outcomes, and clinically relevant bleeding. Trial sequential analysis (TSA) and sensitivity analyses were prespecified (CRD42024608709).

RESULTS: Eight randomized trials encompassing 10,216 patients were included. Short DAPT regimens significantly reduced major bleeding [hazard ratio, 0.50; 95% confidence interval (CI), 0.30-0.85; P = 0.011] compared with standard DAPT. No significant differences were observed in MACE (hazard ratio, 1.21; 95% CI, 0.91-1.64; P = 0.193) or NACE (hazard ratio, 0.94; 95% CI, 0.80-1.10; P = 0.427). The results of TSA reinforced these findings. Other secondary outcomes showed no significant differences, but interpretation was limited by the small number of studies reporting these events.

CONCLUSION: Abbreviated DAPT significantly reduces major bleeding risk in patients with STEMI compared with standard 12-month DAPT, without apparently compromising ischemic protection. However, further research is needed to clarify net clinical outcomes in this high-risk ACS subset.

PROTOCOL REGISTRATION IDENTIFIER: CRD42024608709.

PMID:40530547 | DOI:10.2459/JCM.0000000000001737

Zhonghua Xin Xue Guan Bing Za Zhi. 2025 Jun 24;53(6):653-660. doi: 10.3760/cma.j.cn112148-20240608-00324.

ABSTRACT

Objective: To explore the impact of changes of myocardial infarct size on left ventricular adverse remodeling in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). Methods: This was a prospective cohort study. The STEMI patients who underwent primary PCI in the First Medical Center of the Chinese People's Liberation Army General Hospital, Beijing Anzhen Hospital, Hainan Hospital of the Chinese People's Liberation Army General Hospital and Guangxi Yulin First People Hospital from January 1, 2017 to January 1, 2022 were enrolled. Cardiac magnetic resonance (CMR) was performed to dynamically assess the myocardial infarct size and calculate the rate of infarct size change between the acute phase (5 to 7 days post-primary PCI) and 6-month follow-up. The endpoint was left ventricular adverse remodeling which was defined as an increase of more than 20% in left ventricular end-diastolic volume (LVEDV) assessed by CMR at 6 months after primary PCI compared with LVEDV at 1 week after primary PCI. Based on serial CMR assessments, the patients were divided into left ventricular adverse remodeling group and non-remodeling group. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of infarct size change for left ventricular adverse remodeling, and according to the optimal cutoff value, improved infarct size was defined as a decrease of >20% in the infarct size measured by CMR at 6 months after primary PCI compared with infarct size at 1 week after primary PCI. Multivariate logistic regression analysis was performed to identify the protective factors and risk factors for left ventricular adverse remodeling. Results: A total of 267 patients were enrolled, aged (58±11) years, with 234 males (87.6%). And 73 cases in the left ventricular remodeling group and 194 cases in the non-remodeling group. Infarct size assessed by CMR at 6 months after primary PCI decreased significantly compared with infarct size at 1 week after primary PCI in the left ventricular remodeling group ((23±13)% vs. (27±12)%, P=0.004), the same as in the non-remodeling group ((18±10)% vs. (23±10)%, P<0.001). The area under the ROC curve for the rate of infarct size change in predicting left ventricular remodeling was 0.735 (95%CI 0.670-0.799, P<0.001), a 20% reduction was the optimal cut-off value. Compared to the patients with non-improved infarct size, the incidence of left ventricular adverse remodeling was significantly lower in the patients with improved infarct size (18% (24/133) vs. 37% (49/134), P=0.001). Multivariate logistic regression analysis showed that improvement in IS was a protective factor for left ventricular adverse remodeling (OR=0.376, 95%CI 0.236-0.721, P=0.002). Conclusion: Patients with STEMI who experience obvious reduction in infarct size after primary PCI have a significantly reduced risk of left ventricular adverse remodeling.

PMID:40528603 | DOI:10.3760/cma.j.cn112148-20240608-00324

Expert Rev Cardiovasc Ther. 2025 Jun 17. doi: 10.1080/14779072.2025.2520827. Online ahead of print.

ABSTRACT

INTRODUCTION: Bleeding risk stratification tools are essential for optimizing ischemic protection while minimizing bleeding complications, particularly in patients undergoing percutaneous coronary intervention (PCI) or dual antiplatelet therapy (DAPT).

AREAS COVERED: A structured search of PubMed, Scopus, and Web of Science was conducted for studies published from January 2005 to December 2024. This review evaluates traditional and novel bleeding risk models in MI management. Established tools like CRUSADE, ACUITY-HORIZONS, ACTION, and PRECISE-DAPT aid in predicting in-hospital and early post-discharge bleeding but have limitations in long-term risk assessment and adapting to modern PCI techniques. Emerging models - SWEDEHEART, ARC-HBR, BLEED-MI, CREDO-KYOTO, and BleeMACS - offer enhanced risk stratification by incorporating broader clinical variables and long-term bleeding predictors, improving their applicability to contemporary MI management.

EXPERT OPINION: Despite advancements, current models exhibit moderate predictive accuracy (c-statistics 0.70-0.80) and rely on static baseline factors, limiting real-time applicability. They also fail to integrate ischemic risk assessment, creating challenges in balancing thrombotic and bleeding risks. Future research should focus on AI-driven dynamic risk models, broader validation across diverse populations, and integrating bleeding and ischemic risk stratification into a unified framework. Embedding these tools into electronic health records (EHRs) will enhance clinical decision-making and improve patient outcomes.

PMID:40528388 | DOI:10.1080/14779072.2025.2520827

Acta Pharmacol Sin. 2025 Jun 17. doi: 10.1038/s41401-025-01593-9. Online ahead of print.

ABSTRACT

Ischaemic heart disease is an important cause of death in humans, and resupply of blood to damaged myocardium can exacerbate the risk of cardiac I/R injury. Circular RNAs (circRNAs) play an important role in cardiovascular disease. In this study we investigated the regulatory role of circDhx32 in the progression of I/R injury. Cardiac I/R model was established in mice by ligating the left anterior descending coronary artery (LAD) for 45 min, followed by blood reperfusion for 24 h or 2 weeks. For in vitro study, neonatal mouse ventricular cardiomyocytes were subjected to hypoxia-reoxygenation (H/R) assault. CircDhx32 was significantly upregulated in I/R-treated mice and H/R-treated cardiomyocytes. Cardiomyocyte-specific knockdown of circDhx32 ameliorated the pathological outcomes of cardiac I/R injury including improved cardiac function, reduced infarct size and reduced release of cardiac injury biomarkers. The protective effects of circDhx32 silencing were also observed in cardiomyocytes after H/R. We demonstrated that ALKBH5 functioned as an m6A demethylase, removing the m6A modification sites of circDhx32. Reduced m6A modification inhibited recognition and binding by the m6A readers YTHDF2 and YTHDC1, leading to circDhx32 degradation and diminished nucleoplasmic export under pathological conditions. Elevated circDhx32 inhibited the transcriptional activation of AdipoR1 by binding to FOXO1. Conversely, circDhx32 deficiency alleviated the inflammatory responses in I/R-treated mice and H/R-treated cardiomyocytes including decreased mRNA expression levels and release of inflammatory cytokines such as IL-6, TNF-α and IL-1β potentially through modulation of the AdipoR1-AMPK-NF-κB signaling pathway. In conclusion, ALKBH5 acted as m6A eraser accompanied by the m6A readers YTHDF2 and YTHDC1 to promote high expression and nuclear retention of circDhx32 under pathological conditions. CircDhx32 regulated the inflammatory responses to cardiac I/R injury by targeting the AdipoR1-AMPK-NF-κB signaling pathway, which competed with AdipoR1 for FOXO1. These results reveal a novel mechanism underlying cardiac ischaemic injury, and circDhx32 is expected to be a potential therapeutic target for early intervention in ischaemic cardiac disease.

PMID:40528033 | DOI:10.1038/s41401-025-01593-9

Mol Biol Rep. 2025 Jun 17;52(1):606. doi: 10.1007/s11033-025-10713-x.

ABSTRACT

Necroptosis is a regulated form of programmed cell death. It is integral to the development of various diseases, such as neurological disorders, lung injuries, liver fibrosis, and testicular toxicity. This process is orchestrated by essential molecular pathways that involve receptor-interacting protein kinases (RIP1/RIP3) and mixed lineage kinase domain-like protein (MLKL), which lead to membrane disruption, the release of damage-associated molecular patterns (DAMPs), and subsequent inflammation. Melatonin, recognized for its potent antioxidant and anti-inflammatory properties, has emerged as a promising therapeutic agent that can inhibit necroptosis through various mechanisms. In neurological diseases such as intracerebral hemorrhage, traumatic brain injury, and cerebral ischemia-reperfusion, melatonin suppresses necroptosis by downregulating RIP1/RIP3/MLKL signaling, upregulating A20 (TNFAIP3), and inhibiting the HMGB1/TLR4/NF-κB pathway. In lung disorders, melatonin attenuates cadmium- and LPS-induced necroptosis by modulating the Ang-II axis, reducing TNF-α-mediated signaling, and acting through MT1/MT2 receptors. In liver fibrosis models, melatonin inhibits RIP1-RIP3 necrosome formation, reduces oxidative stress, and decreases DAMPs-mediated immune responses. Similarly, in testicular toxicity induced by tetrabromobisphenol A (TBBPA), melatonin suppresses necroptosis by inhibiting the several pathways and reducing ROS overproduction. These findings highlight melatonin's ability to modulate necroptosis across diverse tissues, offering protection against inflammation, oxidative stress, and cell death. By targeting necroptosis-related pathways, melatonin presents a versatile therapeutic strategy for treating diseases characterized by excessive cell death and inflammation, including stroke, myocardial infarction, pancreatitis, and autoimmune disorders. This review underscores the potential of melatonin as a novel intervention for necroptosis-related pathologies, emphasizing its role in restoring cellular homeostasis and mitigating tissue damage.

PMID:40526280 | DOI:10.1007/s11033-025-10713-x

Echocardiography. 2025 Jun;42(6):e70221. doi: 10.1111/echo.70221.

ABSTRACT

BACKGROUND: Coronary artery disease (CAD) is one of the causes of morbidity and death worldwide. Recently, speckle tracking technologies allowed the assessment of the strain of each myocardial segment in an automated method that may decrease inter-operator variability.

OBJECTIVE: To compare the effectiveness of two-dimensional speckle tracking global longitudinal strain (GLS) during dobutamine stress echocardiography (DSE) with myocardial perfusion imaging (MPI) using single photon emission computed tomography (MPI SPECT) in the diagnosis of CAD.

METHODS: A cross-sectional study was conducted involving 103 patients with CAD suspicion. Each participant underwent MPI SPECT and GLS measurements at rest and during peak dobutamine stress. The outcomes from GLS-DSE and MPI SPECT were then compared against the results of ICA as the reference standard for diagnosis.

RESULTS: The mean age of included patients was 57.79 ± 8.08 years. The MPI-SPECT defect size results demonstrated a highly significant (p value < 0.001) and strong positive correlation with the number of affected vessels in invasive coronary angiography (ICA). The sensitivity and specificity of the MPI SPECT were 90.62% and 92.96%, respectively, with a PPV of 85.29% and an NPV of 95.65%. Additionally, a highly significant (p value < 0.001) and strong negative correlation was observed between GLS values at peak DSE and the number of affected vessels in ICA. GLS at peak DSE had 78.12% sensitivity and 88.73% specificity with PPV 75.76% and NPV 90%.

CONCLUSION: GLS at peak DSE looks to be another noninvasive tool for the assessment of patients with suspected CAD, with the benefits of being a quick, non-expensive, and radiation-free test.

PMID:40526261 | DOI:10.1111/echo.70221

J Med Virol. 2025 Jun;97(6):e70440. doi: 10.1002/jmv.70440.

ABSTRACT

Viral myocarditis is characterized by inflammatory cell infiltration and myocardial damage. However, the involvement of immune cells and the interaction between immune cells and stromal cells remain poorly understood. We successfully established a mouse model of viral myocarditis induced by Coxsackievirus B3 (CVB3) and systematically analyzed immune cell infiltration and myocardial injury at different time points. Single-cell RNA sequencing (scRNA-seq) was performed at the peak of immune cell infiltration to characterize the immune landscape of infected cardiac tissue and peripheral blood mononuclear cells (PBMCs). Macrophage depletion and vascular endothelial growth factor receptor (VEGFR) inhibition were performed to validate the immune-stromal crosstalk. Peak immune cell infiltration and myocardial injury occurred on the 7th day of infection. scRNA-seq revealed that endothelial cells and mononuclear phagocytes (MNPs) were the most substantially expanded cell populations in the hearts of mice with viral infection. Trem2 macrophage, characterized by tissue repair gene signatures, was the predominant MNP subcluster in the infected heart, while tip cells and capillaries were the most expanded endothelial cell clusters. Cell-cell communication analysis identified increased macrophage-endothelial cell interactions during CVB3 infection. Macrophage-derived VEGFA secretion, partially induced by CVB3 infection and apoptotic cardiomyocyte debris, promoted angiogenesis, while macrophage depletion resulted in reduced VEGFA secretion and endothelial proliferation. Moreover, inhibition of VEGFR exacerbated cardiac dysfunction, highlighting the protective role of angiogenesis in myocarditis progression. In summary, these results elucidated a cardioprotective role of macrophage-driven angiogenesis via vascular endothelial growth factor signaling during viral myocarditis, providing new insights into therapeutic strategies for inflammatory heart diseases.

PMID:40525609 | DOI:10.1002/jmv.70440

Cureus. 2025 May 17;17(5):e84268. doi: 10.7759/cureus.84268. eCollection 2025 May.

ABSTRACT

Penetrating cardiac injuries (PCI) from gunshot wounds are among the most fatal forms of trauma, with prehospital mortality rates exceeding 90%. While the right ventricle is most commonly affected due to its anterior location, retained intracardiac projectiles are rarely encountered and pose significant management challenges. Cardiac tamponade, though potentially fatal, can sometimes provide a protective mechanism by limiting hemorrhage. The decision to surgically remove retained bullets remains controversial, particularly in hemodynamically stable patients. We report the case of a 51-year-old male who sustained multiple gunshot wounds, including a thoracic injury with an 8 mm bullet fragment retained in the right ventricle. On arrival, the patient was hemodynamically stable despite imaging revealing a pericardial effusion and a sternal fracture. A median sternotomy with pericardiotomy was performed, revealing a right ventricular epicardial wound without active bleeding. Due to the absence of cardiopulmonary bypass, the intracardiac bullet was not removed. The patient received prophylactic heparin and was monitored with imaging and serial exams. He was discharged without complications. This case highlights a rare presentation of PCI without overt tamponade physiology, despite the presence of a pericardial effusion. The patient remained stable throughout hospitalization, supporting the hypothesis that tamponade can temporarily contain hemorrhage. Conservative management of retained intracardiac projectiles may be appropriate in select patients, particularly when the projectile is embedded in the trabeculated myocardium and the risk of embolization is low. Literature suggests that long-term outcomes can be favorable with nonoperative management in stable cases. This case reinforces the importance of rapid surgical intervention for PCI, even in stable patients, and supports individualized, conservative management of retained cardiac projectiles in the absence of cardiopulmonary bypass. Further research is needed to define standardized protocols for managing intracardiac foreign bodies in trauma.

PMID:40525047 | PMC:PMC12168663 | DOI:10.7759/cureus.84268

Case Rep Cardiol. 2025 Jun 7;2025:3481920. doi: 10.1155/cric/3481920. eCollection 2025.

ABSTRACT

Mechanical circulatory support devices, such as the Impella catheter (Abiomed, Danvers, Massachusetts), continue to become more commonplace in patients undergoing high-risk percutaneous coronary intervention (PCI) or those in cardiogenic shock. Thrombus in the left ventricle is a contraindication to Impella placement. Here, we present a patient with an anterior ST elevation myocardial infarction who underwent primary PCI with subsequent development of cardiogenic shock followed by Impella placement, who then later developed an LV thrombus. The Impella was removed after placement of a Sentinel cerebral protection device (Boston Scientific, Massachusetts). The left carotid filter of the Sentinel captured a thrombus fragment. The patient did not have any neurological compromise. This case represents the first report of actual capture of LV thrombus by a Sentinel system in this context. The case suggests the potential value of the Sentinel cerebral protection device to lower the risk of an embolic event during Impella removal in selective clinical scenarios.

PMID:40524828 | PMC:PMC12170058 | DOI:10.1155/cric/3481920

J Tradit Chin Med. 2025 Jun;45(3):538-551. doi: 10.19852/j.cnki.jtcm.2025.03.010.

ABSTRACT

OBJECTIVE: To investigate the mechanism of Dan Ze mixture (, DZM) in the treatment of lipotoxic cardiomyopathy.

METHODS: Ultra-performance liquid chromatography tandem mass spectrometry was employed to characterize the serum migration constituents of DZM. A lipotoxic cardiomyopathy rat model was established through high-fat diet and intervened by different doses of DZM. The cardiac function was assessed using echocardiography, and hematoxylin and eosin, oil red O, and Masson staining were conducted to evaluate morphological changes, lipid accumulation, and fibrosis in myocardial tissue. Serum myocardial enzyme activity, lipid levels, and lipid content of myocardial tissue were measured, while fluorescent staining and colorimetry were used to assess oxidation levels in myocardial tissue. Mitochondrial membrane potential was detected by 5,5', 6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanineio-dide (JC-1). Transmission electron microscopy was employed to observe ultrastructure and mitochondrial structure changes in myocardial tissue. Fluorescence double staining and colocalization were utilized to observe the binding of autophagosomes and mitochondria, while immunohistochemical staining was used to detect the expression of mitophagy-related proteins. Terminal deoxynucleoitidyl transferase mediated nick end labeling staining was employed for the identification of apoptosis in myocardial tissue, while quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot were utilized for the detection of apoptosis, B-cell lymphoma-2 adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/ mitophagy signaling pathway-related genes and proteins. In palmitic acid-induced Rat H9C2 cardiomyocytes (H9c2) cells, various cellular parameters including cell viability, lactate dehydrogenase release, apoptosis rate, oxidative stress level, mitochondrial structure and function, and mitophagy level were assessed after the treatment of DZM drug-containing serum for a duration of 24 h. The cellular expressions of BNIP3/mitophagy signaling pathway relevant genes and proteins were further evaluated using qRT-PCR and Western blot techniques.

RESULTS: A total of 295 prototypes (e.g., phenolic acids, quinones, terpenoids) were identified in serum of rats after oral administration of DZM. In vivo, DZM therapy has been shown to effectively enhance cardiac function, mitigate high-fat diet-induced myocardial structural damage and lipid accumulation. Furthermore, DZM has demonstrated the ability to reduce lipid levels, attenuate cell apoptosis, combat oxidative stress, enhance mitochondrial structure and function, and activate the BNIP3/mitophagy signaling pathway. Furthermore, the silencing of BNIP3 has been shown to exacerbate palmitic acid-induced damages in H9c2 cells, while inhibiting the BNIP3/mitophagy signaling pathway can mitigate the inhibitory effects of DZM on palmitic acid-induced apoptosis, lipid deposition and oxidative stress.

CONCLUSION: This study presents preliminary evidence for the therapeutic efficacy of DZM on lipotoxic cardiomyopathy through the activating BNIP3/mitophagy signaling pathway.

PMID:40524293 | PMC:PMC12134320 | DOI:10.19852/j.cnki.jtcm.2025.03.010

Free Radic Biol Med. 2025 Jun 14;237:542-557. doi: 10.1016/j.freeradbiomed.2025.06.017. Online ahead of print.

ABSTRACT

Myocardial ischemia-reperfusion injury (MI/RI) is a major contributor to poor outcomes after revascularization in patients with myocardial infarction, largely due to the absence of targeted therapies. Phillygenin (PHI), a bioactive compound isolated from Forsythia suspensa, has been found to confer various pharmacological properties, including anti-inflammatory, hepatoprotective, and renal protective effects. However, the specific role of PHI in MI/RI remains largely unclear. Thus, this study aims to investigate whether PHI exerted cardioprotective effects against MI/RI, and if so, to elucidate the underlying molecular mechanisms. Hypoxia/reoxygenation (H/R) models in H9c2 cardiomyocytes and MI/RI mouse models were established. PHI intervention markedly improved cardiac function, reduced myocardial infarct size, and attenuated cardiomyocyte damage in MI/RI mice. PHI treatment significantly reversed H/R-induced cellular injury and mitochondrial dysfunction in cultured cardiomyocytes. Notably, PHI administration significantly mitigated myocardial cuproptosis, rather than pyroptosis and ferroptosis. Specifically, PHI reduced cardiomyocyte cuproptosis by downregulating the protein expression of ferredoxin 1 (FDX1) and lipoyl synthase (LIAS), and suppressing copper accumulation. Induction of cuproptosis abolished the cardiac benefits of PHI in vivo and in vitro. Mechanistically, PHI promoted the lysosomal localization and degradation of the copper transporter 1 (CTR1), thus alleviating cuproptosis, inflammation, oxidative stress, and mitochondrial injury in cardiomyocytes. Overall, PHI may be a promising therapeutic agent for the alleviation of MI/RI-induced cardiac dysfunction through the inhibition of cuproptosis via facilitating the transfer of CTR1 to the lysosome for degradation.

PMID:40523538 | DOI:10.1016/j.freeradbiomed.2025.06.017

J Cardiovasc Pharmacol. 2025 Jun 16. doi: 10.1097/FJC.0000000000001721. Online ahead of print.

ABSTRACT

Paraquat, a widely used herbicide, is known to induce oxidative stress and inflammation, which leads to myocardial injury. Klotho, a protein with antioxidative and anti-inflammatory properties, has garnered as a potential cardioprotective factor. This study aimed to investigate whether cardiac-specific overexpression of klotho mitigates paraquat-induced myocardial injury through the activation of the NF-E2-related factor-2 (Nrf-2)/antioxidant response element (ARE) signaling pathway. Our results revealed that both mRNA and protein expressions of Klotho were significantly reduced in the myocardial tissue of paraquat-exposed rats. However, cardiac-specific overexpression of Klotho significantly restored Klotho levels and attenuated paraquat-induced myocardial injury, as evidenced by the decreased lactate dehydrogenase (LDH) and cardiac troponin I (cTnI) contents, and creatine kinase (CK) activity, alongside with apoptosis. Furthermore, cardiac-specific overexpression of Klotho inhibited oxidative stress and inflammation in myocardial tissue of paraquat-subjected rats. Mechanistically, Klotho activated of the Nrf2/ARE signaling pathway, upregulating cytoprotective genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate cysteine ligase catalytic (GCLC) subunit, and glutamate cysteine ligase modifier (GCLM) subunit. Our findings indicate that Klotho protects against paraquat-induced myocardial injury by suppressing oxidative stress and inflammation, primarily via the activation of the Nrf2/ARE signaling pathway. These results underscore the potential therapeutic role of Klotho in preventing paraquat-induced myocardial damage.

PMID:40521670 | DOI:10.1097/FJC.0000000000001721

Theranostics. 2025 May 15;15(13):6253-6254. doi: 10.7150/thno.115473. eCollection 2025.

ABSTRACT

[This corrects the article DOI: 10.7150/thno.15162.].

PMID:40521208 | PMC:PMC12159842 | DOI:10.7150/thno.115473

Cytotechnology. 2025 Aug;77(4):122. doi: 10.1007/s10616-025-00759-x. Epub 2025 Jun 11.

ABSTRACT

Atherosclerosis is a progressive pathological disorder resulting in various vital cardiovascular diseases such as myocardial infarction and stroke, leading to high mortality worldwide. Currently, the precise mechanisms of pathogenesis and progression of atherosclerosis remained unclear. Circular RNAs (circRNAs) have been implicated in vital processes of cardiovascular disease. In this study, we aimed to investigate the roles of circSirt1 in vascular smooth muscle cell (VSMC) injury during atherosclerosis. We found circSirt1 was significantly downregulated in VSMCs from atherosclerosis patients compared with those from healthy controls. Under oxidative stress, expression of circSirt1 was remarkedly suppressed in VSMCs. Notably, overexpression of circSirt1 effectively protected the oxidative stress-induced VSMC injury. On the other way, miRNA-27b-3p was high-expressed in VSMCs from atherosclerosis patients and was effectively induced under oxidative stress. Overexpression of miR-27b-3p exacerbated the oxidative stress-induced VSMC injury. From the non-coding RNA service, starBase, circSirt1 was predicted to interact with miR-27b-3p. This association was further validated by RNA pull-down and luciferase assays. We detected glutamine metabolism rate was depressed under oxidative stress and low glutamine supply rendered VSMCs more susceptible to oxidative stress. Furthermore, we identified the glutamine metabolism key enzyme, glutaminase (GLS) as a direct target of miR-27b-3p in VSMCs. miR-27b-3p blocked glutamine metabolism and promoted VSMC cell injury through direct targeting GLS. Finally, rescue experiments verified the circSirt1-protected VSMC injury was through regulating the miR-27b-3p-GLS axis that restoration of miR-27b-3p in circSirt1-overexpressed VSMCs successfully overrode the high-circSirt1-moduated miR-27b-3p and GLS expressions and the oxidative stress-induced VSMC injury. Summarily, these results unveiled vital roles and molecular mechanisms of circSirt1 in oxidative stress-induced VSMC injury during atherosclerosis by regulating the miR-27b-3p-GLS axis, indicating rescue of circSirt1 in VSMCs could be an effectively therapeutic approach to treat atherosclerosis.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-025-00759-x.

PMID:40521053 | PMC:PMC12158877 | DOI:10.1007/s10616-025-00759-x

Front Cardiovasc Med. 2025 May 30;12:1535401. doi: 10.3389/fcvm.2025.1535401. eCollection 2025.

ABSTRACT

Cardiovascular disease (CVD) remains a leading cause of death globally, posing a major public health challenge. Due to the complexity of CVD's etiology, understanding its pathogenesis has been a significant challenge and research focus. In recent years, the communication between organelles has gained increasing attention, with mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) emerging as a key structural component that facilitates dialogue between the mitochondria and the ER. Numerous studies have highlighted that proteins located in MAMs may play a role in the development of CVD. Among these, mitofusin 2 (MFN2), a protein found on the outer mitochondrial and ER membranes, has garnered particular interest due to its widespread presence in MAMs. This review aims to sort out current research on MFN2, focusing on its potential involvement in myocardial protection through its mediation of MAMs. We discuss how MFN2-mediated MAMs may contribute to the protection against various CVDs, including myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, dilated cardiomyopathy, pathological myocardial hypertrophy, cardiotoxicity, and heart failure. However, given the functional diversity of MFN2, the current body of research remains controversial, and further studies are urgently needed to clarify its precise mechanisms of action.

PMID:40520935 | PMC:PMC12163069 | DOI:10.3389/fcvm.2025.1535401

Cureus. 2025 May 13;17(5):e84064. doi: 10.7759/cureus.84064. eCollection 2025 May.

ABSTRACT

Right-sided heart failure (RHF) remains a clinically challenging and under-researched condition often managed through extrapolated guidance from left-sided heart failure data. This review explores the therapeutic promise of empagliflozin, a sodium-glucose co-transporter 2 inhibitor, for RHF management. While empagliflozin is currently approved for glycemic control and heart failure with reduced ejection fraction, its potential to improve symptoms, functional capacity, and cardiovascular outcomes in RHF warrants focused investigation. In the absence of RHF-specific randomized controlled trials (RCTs), this review synthesizes insights from preclinical models, subgroup analyses, and surrogate markers drawn from major trials such as EMPEROR-Reduced, EMPEROR-Preserved, and EMPIRE-HF. Empagliflozin's mechanisms are conceptually grouped as hemodynamic, reducing preload, afterload, and venous congestion, and improving right ventricle-pulmonary artery coupling and metabolic, enhancing myocardial energetics, reducing inflammation and fibrosis, and inhibiting the Na⁺/H⁺ exchanger (NHE1). Although RHF patients were not separately stratified in these trials, indirect benefits observed through TAPSE improvement, renal protection, and congestion relief support further exploration. This review emphasizes the need for RHF-specific RCTs, mechanistic studies, and real-world cohorts to validate and expand empagliflozin's therapeutic scope. Overall, empagliflozin emerges as a mechanistically sound and clinically promising candidate for transforming the management of RHF by targeting both cardiac and renal dysfunction.

PMID:40519498 | PMC:PMC12163198 | DOI:10.7759/cureus.84064

Int J Cardiol Cardiovasc Risk Prev. 2025 May 29;26:200443. doi: 10.1016/j.ijcrp.2025.200443. eCollection 2025 Sep.

ABSTRACT

BACKGROUND: S100A4 plays a crucial role in myocardial ischemia-reperfusion injury (MIRI), where the interplay between autophagy and inflammation shapes the progression of reperfusion injury. However, the specific mechanisms by which S100A4 influences autophagy and inflammation in this context remain unclear.

METHODS: An ischemia-reperfusion (I/R) model was established in mice. The optimal timing for inducing reperfusion injury was determined, and mice were divided into sham and experimental groups. The experimental group underwent 2 h of ischemia/reperfusion injury followed by a 2-day reperfusion period. In the I/R + S100A4-shRNA group, S100A4 silencing was achieved through the injection of short hairpin RNA (shRNA). Myocardial ischemia was induced by occluding the left anterior descending branch (LAD) of the coronary artery. Diagnostic procedures, including electrocardiogram assessments, cardiac function testing, cardiac enzyme analyses, and 2,3,5-triphenyl tetrazolium chloride (TTC) staining, were performed to assess myocardial injury. Immunohistochemistry, immunofluorescence staining, hematoxylin-eosin (HE) staining, and Masson trichrome staining were used to evaluate the expression levels of IL-1, TNF-a, morphological changes in cardiomyocytes, and cardiac fibrosis. Protein blotting was conducted to examine autophagy-related proteins and Bnip3 signaling-related proteins.

RESULTS: The study showed an increase in S100A4 expression, as well as upregulation of autophagy orchestrating proteins (Beclin-1 and LC3), contributing to myocardial injury and expansion of myocardial infarction (MI). S100A4 played a multifaceted role by regulating autophagy through the BNIP3 pathway in MIRI. Silencing S100A4 resulted in reduced autophagy and inflammation, leading to decreased infarct size and improved cardiac function.

CONCLUSIONS: S100A4 is upregulated during MIRI and orchestrates autophagy through the BNIP3 pathway, influencing the progression of reperfusion injury following myocardial infarction. Inhibition of autophagy and mitigation of inflammatory responses by S100A4-shRNA provide protection against the detrimental effects of IRI on the heart.

PMID:40519234 | PMC:PMC12164005 | DOI:10.1016/j.ijcrp.2025.200443