Protección miocárdica

Cells. 2025 Sep 16;14(18):1452. doi: 10.3390/cells14181452.

ABSTRACT

Sepsis-induced cardiomyopathy is a life-threatening complication lacking targeted therapies. While empagliflozin (Empa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, confers robust cardioprotection, its specific efficacy in treating sepsis-induced cardiomyopathy and the Empa mechanisms remain poorly defined, limiting its targeted therapeutic use. In this study, we investigated Empa's effects and its novel mechanisms in a murine lipopolysaccharide (LPS)-induced model of septic cardiomyopathy. Empa pre-treatment effectively prevented LPS-induced cardiac dysfunction, preserving ejection fraction and mitigating myocardial injury (assessed by histology and ELISA) and fibrosis. Transcriptomic analysis revealed that Empa's protective effects were profoundly linked to the preservation of cardiomyocyte cytoskeletal pathways, alongside its anti-inflammatory actions. The results indicate that LPS induced a pathological dissociation of the matrix protein Integrin α5 (ITGA5) from the cell-cell adhesion protein Desmocollin-2 (DSC2), a structural disruption completely abrogated by Empa in vivo. This ITGA5-DSC2 stabilization was further confirmed to be a cardiomyocyte-intrinsic effect, recapitulated in vitro in both neonatal mouse cardiomyocytes and human AC16 cells. Building on this mechanistic insight, a computational design was successfully employed to develop 13 novel helical protein binders specifically targeting the ITGA5, yielding candidates with favorable structural properties as potential therapeutic leads. These findings establish the cardiomyocyte structural homeostasis via the ITGA5-DSC2 adhesion axis as a novel, key SGLT2-independent mechanism for empagliflozin's cardioprotection, revealing promising new therapeutic approaches for sepsis-induced cardiomyopathy.

PMID:41002417 | PMC:PMC12468141 | DOI:10.3390/cells14181452

Drug Dev Res. 2025 Nov;86(7):e70171. doi: 10.1002/ddr.70171.

ABSTRACT

‌Oleuropein (OLEU), a natural polyphenol, exhibits cardioprotective potential through mitochondrial modulation, yet its precise mechanisms remain elusive. This study elucidates OLEU's role in alleviating oxidative stress and regulating mitochondrial quality control via the PINK1/Parkin pathway. In vitro, H9C2 cardiomyocytes exposed to H₂O₂-induced oxidative stress were treated with OLEU (0-200 μM), and analyses included cell viability, ROS, SOD, MDA, ΔΨm, ATP, PINK1/Parkin expression and detection of Mitophagic Flux. In vivo, myocardial infarction (MI) was induced in SD rats via coronary ligation, followed by OLEU administration, with assessments of cardiac function, histopathology, and mitophagy using echocardiography, electron microscopy, immunohistochemistry and immunofluorescence. Results showed that OLEU (≤200 μM) dose-dependently restored cell viability, reduced ROS, and normalized SOD/MDA (p < 0.05), while mitigating ΔΨm collapse and ATP depletion, indicating enhanced mitochondrial bioenergetics. OLEU upregulated PINK1/Parkin, promoting mitophagic clearance of damaged mitochondria, and metabolomic analysis revealed modulation of arginine/proline and lipid pathways. In MI rats, OLEU attenuated ROS, preserved myocardial structure, and improved cardiac function, supported by elevated mitophagy in electron microscopy. These findings demonstrate that OLEU protects cardiomyocytes by suppressing oxidative stress, stabilizing mitochondrial integrity, and activating PINK1/Parkin-mediated mitophagy, highlighting its therapeutic potential for myocardial injury and mitochondrial dysfunction.

PMID:41001689 | DOI:10.1002/ddr.70171

Res Sq [Preprint]. 2025 Sep 17:rs.3.rs-7556256. doi: 10.21203/rs.3.rs-7556256/v1.

ABSTRACT

Background: Disrupted cardiomyocyte energy metabolism is a hallmark of heart failure with preserved ejection fraction (HFpEF). Succinate, a key intermediate of the tricarboxylic acid cycle, is markedly decreased in HFpEF myocardium. Beyond its metabolic role, succinate functions as a signaling molecule that activates GPR91 to regulate metabolic and immune pathways. However, the precise contributions and mechanisms of cardiomyocyte succinate-GPR91 signaling in HFpEF pathogenesis remain largely unknown. Methods: HFpEF models were established in wild-type, global GPR91 knockout, and cardiomyocyte-specific GPR91 knockout mice with or without succinate supplementation. Cardiac structure, function, and metabolic phenotypes were assessed using echocardiography, histology, and molecular assays. Transcriptome sequencing of myocardial tissues was performed to identify succinate-GPR91-dependent signaling pathways. Mechanistic studies in isolated cardiomyocytes were conducted to validate pathway regulation and clarify downstream molecular mechanisms. Rescue experiments were further carried out to confirm the functional relevance of succinate-GPR91 signaling in cardiomyocyte metabolism and HFpEF progression. Results: Cardiac succinate levels and GPR91 expression were markedly decreased in HFpEF mice. Succinate supplementation restored systemic metabolism, improved diastolic function, and attenuated myocardial hypertrophy and fibrosis in wild-type (WT) HFpEF mice, but these protective effects were lost in both global Gpr91⁻/⁻ and cardiomyocyte-specific Gpr91 ΔCM knockouts. Transcriptomic analysis demonstrated that succinate activated AMPK signaling and enriched pathways related to glucose-lipid metabolism and NAD⁺ biosynthesis in Gpr91 fl/fl but not in Gpr91 ΔCM hearts. Mechanistically, succinate enhanced AMPK phosphorylation and NAD⁺ production via Gq-mediated signaling, thereby promoting metabolic reprogramming. Conclusion: These findings identify the succinate-GPR91 axis as a critical regulator of cardiometabolic homeostasis and a potential therapeutic target in HFpEF.

PMID:41001528 | PMC:PMC12458547 | DOI:10.21203/rs.3.rs-7556256/v1

Bull Exp Biol Med. 2025 Jul;179(3):305-311. doi: 10.1007/s10517-025-06479-8. Epub 2025 Sep 25.

ABSTRACT

Class III antiarrhythmic drugs used for the treatment of supraventricular tachyarrhythmias can induce polymorphic ventricular tachycardia known as "torsade de pointes" (TdP). This adverse side effect of antiarrhythmic drugs is more pronounced in impaired ventricular perfusion and limits the use of the drugs. In this work, the effects of the antiarrhythmic drug cavutilide were studied in a model of phenylephrine-induced potentiation of TdP. Cavutilide was administered acutely in combination with phenylephrine in non-anesthetized rabbits under continuous ECG monitoring. Cavutilide in the presence of phenylephrine induced pronounced ventricular extrasystoles almost without episodes of ventricular tachycardia or TdP paroxysms. The reference antiarrhythmic drug dofetilide under the same model conditions caused prolonged, multiple episodes of monomorphic ventricular tachycardia and frequent, repetitive paroxysms of high-frequency TdP. Thus, cavutilide demonstrates very low tendency to induce TdP under conditions of impaired myocardial perfusion, which can be explained by direct type of the dependence of its effect on the frequency of myocardium activation.

PMID:40996652 | DOI:10.1007/s10517-025-06479-8

Physiol Rep. 2025 Sep;13(18):e70580. doi: 10.14814/phy2.70580.

ABSTRACT

This study investigated the effects of high-intensity interval training (HIIT) on endoplasmic reticulum (ER) stress, ferroptosis, and iron deposition in rats with heart failure (HF). HF was induced by intraperitoneal injection of isoprenaline (130 mg/kg/day) for 4 days. Afterward, rats were divided into control healthy (Control), HF sedentary (HF-Sed), and HF HIIT (HF-HIT) groups. The HF-HIT group underwent HIIT (5 intervals of 4 min at 85%-90% VO2max, separated by 2 min at 50%-60% VO2max) for 8 weeks. Biomarkers of ER stress, ferroptosis, and oxidative stress, along with cardiac function, were measured post-intervention. HIIT reduced cardiac fibrosis and iron deposition while increasing cystine/glutamate transporter (SLC7A11), glutathione peroxidase 4 (GPX4), and SOD levels. Additionally, protein levels of glucose-regulated protein 78 (GRP78), protein kinase RNA-activated-like ER kinase (PERK), and activating transcription factor 4 (ATF4) decreased after HIIT. These findings suggest that HIIT alleviates ferroptosis and ER stress via the PERK/ATF4/SLC7A11/GPX4 pathway, offering protective effects against HF.

PMID:40999314 | PMC:PMC12463575 | DOI:10.14814/phy2.70580

Kyobu Geka. 2025 Sep;78(10):775-780.

ABSTRACT

Transesophageal echocardiography (TEE) is a valuable diagnostic and intraoperative tool that allows high-resolution, real-time imaging of deep cardiovascular structures without interfering with surgery. It offers dynamic information similar to computed tomography (CT) or magnetic resonance imaging (MRI) but without radiation exposure, making repeated assessments feasible. During cardiovascular surgery, TEE guides cannula placement, monitors myocardial protection, detects complications like air embolism and intraoperative aortic dissection, and facilitates real-time surgical navigation. Its utility extends to postoperative intensive care unit (ICU) care and emergency settings, where it helps diagnose complications when CT is not feasible. In thoracic surgery, TEE aids in assessing tumor invasion into cardiovascular structures. However, TEE's effectiveness heavily relies on the operator's skill, unlike the objectivity of radiologic modalities. Thus, fostering collaboration between anesthesiologists and surgeons is essential. As a critical part of perioperative management, TEE proficiency is now a requirement for board certification in cardiovascular anesthesia in Japan. Supporting anesthesiologists in developing TEE skills enhances surgical outcomes and institutional capability.

PMID:40998339

PLoS One. 2025 Sep 25;20(9):e0333027. doi: 10.1371/journal.pone.0333027. eCollection 2025.

ABSTRACT

OBJECTIVE: The aim of this study was to explore the differentially expressed miRNAs in the hearts of rats protected from early spontaneous hypertension by blood flow-restricted resistance training and to elucidate the effects of blood flow-restricted resistance training on the expression of these genes.

METHODS: Four-week-old SHRs and WKY rats were used and randomly divided into five groups: the normal group (WKY), SHR control group (SHR-SED), high-intensity resistance training group (HIRT), medium-intensity resistance training group (MIRT), and blood flow-restricted medium-intensity resistance training group (BFRT). During the experiment, the body weight, cardiac function and hemodynamic parameters of the rats were measured. After training, total RNA was extracted from the left ventricular myocardium of rats in the SHR-SED group and the BFRT group, miRNAs were sequenced, followed by GO enrichment and KEGG pathway analyses, and the differentially expressed miRNAs were subsequently validated via qRT‒PCR.

RESULTS: 1) Hemodynamic tests revealed that the blood pressure of SHRs in the BFRT decreased significantly and that the blood pressure level of SHRs in the BFRT decreased more significantly than that of the simple resistance training groups did (P < 0.05). 2) Cardiac function tests revealed that the EF, FS, and MV E/A of SHRs in the BFRT significantly increased, whereas the HR, IVSd, IVSs, LVIDd, LIVDs, LVPWd, LVPWs and LV mass significantly decreased (P < 0.05). 3) Transcriptome sequencing revealed 9 differentially expressed miRNAs in the BFRT group compared with the SHR-SED group (2 miRNAs were significantly upregulated, and 7 miRNAs were significantly downregulated), with P < 0.05 and |log2FoldChange| ≥ 1 used as the criteria for differential significance. The most prominent differentially expressed miRNA was miR-200b-3p (P = 0.00, |log2FoldChange| = 2.45). 4) The miRNA validation results revealed that BFRT significantly reduced the expression of miR-200a-3p, miR-200b-3p, miR-342-3p, miR-350, miR-429, miR-1249, miR-1949 in SHR myocardium, and increased the expression of miR-31a-5p and miR-224-5p (P < 0.01).

CONCLUSION: Eight weeks of blood flow-restricted medium-intensity resistance training could lower SHR blood pressure, and it might also improve early SHR cardiac function by regulating the expression of miR-224-5p, miR-31a-5p, miR-200b-3p, miR-200a-3p, miR-342-3p, miR-429, miR-1949, miR-1249, and miR-350, with the differential expression of miR-200b-3p being particularly significant.

PMID:40997050 | PMC:PMC12463276 | DOI:10.1371/journal.pone.0333027

Front Pharmacol. 2025 Sep 9;16:1624595. doi: 10.3389/fphar.2025.1624595. eCollection 2025.

ABSTRACT

BACKGROUND: Research has underscored the significance of targeting energy metabolic remodeling in heart failure (HF) as a crucial therapeutic avenue in recent years. Following the onset of heart failure, dysregulated energy metabolism induces multiple adverse effects, exemplified by the reduced expression of connexin 43 (Cx43)-a gap junction protein requiring substantial ATP for phosphorylation modification-in rats with post-myocardial infarction (MI) heart failure. In this study, we report that Wenxin Keli (also known as Wenxin granule), a clinically available Chinese patent medicine used for preventing and treating heart failure-related arrhythmias, modulates energy metabolism and improves Cx43 function by activating AMPK/SIRT1/PGC-1α signaling pathway. However, the pathological alterations after heart failure are intricate, and the underlying mechanism through which Wenxin Keli exerts its therapeutic effect on heart failure remains to be further elucidated.

METHODS: A post-myocardial infarction heart failure rat model was established via left anterior descending coronary artery ligation. Cardiac function was evaluated 4 weeks later using echocardiography, HE, and Masson trichrome staining. ELISA was employed to detect energy metabolism-related indices, while WB analysis was used to quantify the expression levels of proteins, including SIRT1, PGC-1α, and Cx43. IHC was further utilized to assess Cx43 protein content in tissue sections. Ventricular fibrillation (VF) was induced to determine the VF threshold, providing insights into arrhythmogenic susceptibility.

RESULTS: Wenxin Keli enhances energy metabolism and improves Cx43 function in post-MI heart failure rats by activating the AMPK/SIRT1/PGC-1α signaling pathway. Specifically, Wenxin Keli stimulates the SIRT1/PGC-1α axis, promoting interaction between PGC-1α and PPARs and ERRs. This dual mechanism addresses the combined impairments in fatty acid oxidation and glucose utilization after heart failure, restoring mitochondrial oxidative phosphorylation and increasing ATP production through the TCA cycle. Furthermore, Wenxin Keli boosts the positive regulatory effect of SIRT1 on PGC-1α by upregulating AMPK phosphorylation, thereby further activating the AMPK/SIRT1/PGC-1α signaling pathway and creating a positive feedback loop.

CONCLUSION: Wenxin Keli exhibits multi-target regulation of energy metabolic disorders in post-myocardial infarction heart failure while protecting Cx43. Its core mechanism is activating the AMPK/SIRT1/PGC-1α signalling pathway and its downstream regulatory network.

PMID:40994651 | PMC:PMC12455355 | DOI:10.3389/fphar.2025.1624595

Nat Commun. 2025 Sep 24;16(1):8363. doi: 10.1038/s41467-025-62285-w.

ABSTRACT

During development, myocardial contractile force and intracardiac hemodynamic shear stress coordinate the initiation of trabeculation. While Snail family genes are well-recognized transcription factors of epithelial-to-mesenchymal transition, snai1b-positive cardiomyocytes are sparsely distributed in the ventricle of zebrafish at 4 days post-fertilization. Isoproterenol treatment significantly increases the number of snai1b-positive cardiomyocytes, of which 80% are Notch-negative. CRISPR-activation of snai1b leads to 51.6% cardiomyocytes forming trabeculae, whereas CRISPR-repression reduces trabecular cardiomyocytes to 6.7% under isoproterenol. In addition, 36.7% of snai1b-repressed cardiomyocytes undergo apical delamination. 4-D strain analysis demonstrates that isoproterenol increases the myocardial strain along radial trabecular ridges in alignment with the snai1b expression and Notch-ErbB2-mediated trabeculation. Single-cell and spatial transcriptomics reveal that these snai1b-positive cardiomyocytes are devoid of some epithelial-to-mesenchymal transition-related phenotypes, such as Col1a2 production and induction by ErbB2 or TGF-β. Thus, we uncover snai1b-positive cardiomyocytes that are mechanically activated to initiate delamination for cardiac trabeculation.

PMID:40993149 | DOI:10.1038/s41467-025-62285-w

Open Heart. 2025 Sep 23;12(2):e003648. doi: 10.1136/openhrt-2025-003648.

ABSTRACT

BACKGROUND: Sudden cardiac death (SCD) is a common cause of cardiovascular mortality, often triggered by ventricular arrhythmias in the setting of myocardial vulnerability. The wearable cardioverter-defibrillator (WCD) offers temporary protection against SCD, particularly when an implantable device is contraindicated or premature.

OBJECTIVES: We conducted a comprehensive meta-analysis to assess the effectiveness of the WCD in appropriately terminating life-threatening arrhythmias such as sustained ventricular tachycardia (VT) and ventricular fibrillation (VF), preventing sudden cardiac death.

METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we systematically reviewed 40 studies comprising 59 647 adults fitted with a WCD for primary or secondary SCD prevention. Random-effects meta-analysis, subgroup analysis, meta-regression and sensitivity analyses were performed.

RESULTS: The pooled incidence of appropriate WCD intervention was 3% (95% CI 2% to 3%), with substantial heterogeneity (I²=88.9%). The prediction interval ranged from 1% to 8%, indicating that future studies conducted in selected high-risk populations may observe significantly higher WCD intervention. Life-threatening arrhythmias were higher during early follow-up (≤60 days). An appropriate daily WCD wearing time significantly influenced the results. Gender, age, ejection fraction and study design were not significant modifiers. No publication bias was detected.

CONCLUSIONS: The WCD represents an effective strategy for preventing SCD in early high-risk settings, with its benefit closely linked to adherence and appropriate patient selection.

PMID:40992797 | PMC:PMC12458791 | DOI:10.1136/openhrt-2025-003648

Ann Vasc Surg. 2025 Sep 22:S0890-5096(25)00619-3. doi: 10.1016/j.avsg.2025.09.014. Online ahead of print.

ABSTRACT

OBJECTIVE: Postoperative stroke and myocardial infarction (MI) are associated with devastating postoperative morbidity and mortality, therefore limiting the protective effect of carotid revascularization procedures. Moreover, there seems to be a relationship between the severity of stroke and the type of carotid revascularization technique. We aim to investigate the impact of in-hospital stroke or MI on one-year survival following carotid endarterectomy (CEA), transfemoral carotid artery stenting (TFCAS), and transcarotid artery revascularization (TCAR).

METHODS: This is a retrospective analysis of patients undergoing CEA, TFCAS, and TCAR in the VQI database (2016-2023). Our primary outcome was one-year mortality in patients who developed in-hospital stroke or MI following carotid revascularization. Kaplan-Meier survival estimate and multivariable Cox regression analysis were applied to calculate hazard ratios (HR) after adjusting for potential confounders. Additionally, we conducted sub-analyses based on patients' symptomatic status.

RESULTS: Our study included 125,513 (61.8%) CEA, 25,875 (12.8%) TFCAS, and 51,545 (25.4%) TCAR. Compared to patients who did not have a postoperative stroke, the hazard of 1-year mortality was higher for those who did have a stroke following CEA (adjusted hazards ratio [aHR] = 5.9[95%CI:5.1-6.8] P<0.001), TFCAS (aHR=4.2[95%CI:3.7-5.3] P<0.001), and TCAR (aHR=5.2[95%CI:4.1-6.5] P<0.001). The hazards of 1-year mortality after in-hospital MI were also higher following CEA (aHR=3.8[95%CI:3.1- 4.6] P<0.001), TFCAS (aHR=3.5[95%CI:2.3- 5.5] P<0.001), and TCAR (aHR=5.1[95%CI:3.6- 7.2] P<0.001). This trend persisted in sub-analysis based on symptomatic status. At one year, TFCAS showed the lowest survival following an in-hospital stroke or MI. There was no significant difference in one-year mortality among patients who developed in-hospital stroke between TCAR and CEA (aHR=0.93[95%CI:0.73- 1.2] P=0.55). On the other hand, TFCAS was associated with a 50% higher mortality hazard than CEA (aHR=1.5[95%CI:1.1-2.1] P=0.003), and TCAR was associated with a 30% reduction in one-year mortality compared to TFCAS (aHR=0.7[95%CI:0.55-0.94] P=0.015) among patients who developed in-hospital stroke.

CONCLUSION: This large multicenter study reveals critical insights into the impact of in-hospital major adverse events on one-year survival following carotid revascularization. The analysis indicates a significant increase in the hazard of one-year mortality following in-hospital stroke and MI. In patients who developed in-hospital stroke or MI, there was no significant difference in one-year survival between TCAR and CEA. On the contrary, among patients who developed in-hospital stroke or MI, TFCAS was associated with significantly higher mortality compared to CEA and TCAR. This study highlights the importance of selecting the appropriate revascularization method for each patient to improve one-year survival.

PMID:40992493 | DOI:10.1016/j.avsg.2025.09.014

Phytomedicine. 2025 Sep 15;148:157260. doi: 10.1016/j.phymed.2025.157260. Online ahead of print.

ABSTRACT

BACKGROUND: Rehabilitation exercise after acute myocardial infarction is helpful for cardiac function recovery. Isatin, an endogenous indole derivative of tryptophan metabolism, exhibits anti-inflammatory and antioxidant properties, but its role in myocardial injury repair post-myocardial infarction (MI) remains unclear.

PURPOSE: This study aimed to investigate isatin's cardioprotective effects and molecular mechanisms in post-rehabilitation AMI patients through multi-omics approaches.

STUDY DESIGN: This study aimed to systematically investigate the protective effects and molecular mechanisms of isatin on cardiac injury in patients with AMI following rehabilitation, using untargeted metabolomics, HuProt™ microarray, network pharmacology (NP), surface plasmon resonance (SPR), molecular docking, molecular dynamics (MD), animal models, and cell experiments.

METHODS: Serum isatin levels were measured in STEMI patients' pre-/post-Enhanced external counterpulsation (EECP) rehabilitation using untargeted metabolomics. HuProtTM microarray and NP was used to identify the downstream targets of isatin, validated through SPR, molecular docking, and dynamics. A murine AMI model was applied to assess the protective function of isatin. H2O2-treated cardiomyocytes and LPS-treated macrophages were used to explore the potential protective mechanisms of isatin.

RESULTS: EECP elevated serum isatin in STEMI patients, correlating with better cardiopulmonary function. S100A8 was identified as the primary target by HuProt™ microarray and NP. Isatin formed a 2.1 Å hydrogen bond with S100A8-GLU41. SPR KD=57.9 μM; Docking score=-5.37 kcal/mol; MD ΔG=-15.35 ± 1.95 kcal/mol. Isatin improved cardiac function in AMI mice. Isatin enhanced HL-1 cardiomyocyte viability while reducing apoptosis, and decreased macrophage IL-1β, IL-6, IL-1α, and TNF-α secretion.

CONCLUSION: This study demonstrates that EECP enhances cardiac rehabilitation in STEMI patients by upregulating endogenous isatin, which exerts cardioprotective effects through direct targeting of S100A8, leading to improved cardiac function and reduced oxidative stress and inflammation, with the molecular mechanism confirmed by integrated multi-omics analyses.

PMID:40992064 | DOI:10.1016/j.phymed.2025.157260

Cardiovasc Toxicol. 2025 Sep 24. doi: 10.1007/s12012-025-10062-y. Online ahead of print.

ABSTRACT

Ventricular aneurysm is a serious complication following myocardial infarction. Increasing evidence suggests that exercise-based cardiac rehabilitation plays a protective role in cardiovascular disease. However, the effects of exercise on ventricular aneurysm and the underlying mechanisms remain poorly understood. Therefore, this study aimed to establish a murine model of ventricular aneurysm and investigate the impact of exercise on this condition, along with its potential mechanisms. In this study, using proximal coronary artery ligation, a murine cardiac ventricular aneurysm model was established and evaluated by real-time myocardial contrast echocardiography. Wild-type male C57BL/6 mice with ventricular aneurysms were randomly assigned to three groups: a Sedentary group (no exercise, n = 7), a moderate-intensity exercise group (5 m/min adaptive exercise for 2 weeks, followed by 12-m/min moderate-intensity exercise for 8 weeks, n = 9), and a high-intensity exercise group (5-m/min adaptive exercise for 2 weeks, followed by 18-m/min high-intensity exercise for 8 weeks, n = 7). After 8 weeks of exercise intervention, moderate-intensity exercise was found to significantly enhance cardiac function, reduce myocardial fibrosis, and inhibit fibroblast activation. In contrast, high-intensity exercise resulted in deteriorated cardiac function and aggravated cardiac injury. Mechanistically, this paradoxical effect was linked to the regulation of PTEN stability and subsequent modulation of Smad2/3 signaling pathway. This study provides a theoretical foundation for the role of exercise in managing ventricular aneurysms and offers insights into optimal exercise intensity levels.

PMID:40991159 | DOI:10.1007/s12012-025-10062-y

J Inflamm Res. 2025 Sep 17;18:12929-12948. doi: 10.2147/JIR.S527105. eCollection 2025.

ABSTRACT

PURPOSE: To investigate the synergistic protective effects and underlying mechanisms of combining Acorus gramineus rhizoma volatile oil (VOA), known for its "Cardiotropic-channel-directing" properties, with Crebanine (Cre) in MIRI.

PATIENTS AND METHODS: An MIRI model was established in Sprague-Dawley rats to evaluate the synergistic cardioprotective effects of VOA combined with Cre. Myocardial injury was assessed by measuring the infarct size, apoptotic cardiomyocytes, myocardial injury biomarkers, and histopathological changes. Proinflammatory mediators and oxidative stress markers and results of Western blotting were analyzed to determine the underlying cardioprotective mechanisms of Cre and VOA. In addition, metabolomic analysis was conducted to identify alterations in relevant metabolic pathways.

RESULTS: Cre and VOA alleviated MIRI in rats by reducing infarct size, lowering the levels of myocardial injury biomarkers (Lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase (CK), and creatine kinase-myocardial band (CK-MB)), and ameliorating histopathological damage. Mechanistically, Cre and VOA attenuated oxidative stress by enhancing the activity of the antioxidant enzyme superoxide dismutase (SOD) and suppressing the expression of the oxidative stress marker malondialdehyde (MDA). In addition, they downregulated proinflammatory cytokines (interleukin-6 (IL-6) and interleukin-1β (IL-1β)) by inhibiting the MAPK/NF-κB/TNF-α signaling pathway. They mitigated endoplasmic reticulum (ER) stress and apoptosis by modulating the GRP78-PERK/ATF6-CHOP pathway. Metabolomic analysis identified 13 potential biomarkers, and glutamic, pantothenic, and oleic acids were the key metabolites. The glycine, serine, and threonine metabolism pathway, glutathione metabolism, the pentose phosphate pathway, and the biosynthesis of unsaturated fatty acids were the most relevant metabolic pathways involved in the cardioprotective effects of Cre and VOA.

CONCLUSION: Cre and VOA may alleviate MIRI by modulating energy metabolism and suppressing apoptosis and inflammatory responses triggered by oxidative and ER stress. This effect is mediated by GRP78-PERK/ATF6-CHOP and MAPK-NF-κB-TNF-α signaling pathways. Moreover, the volatile oil of Acorus tatarinowii significantly enhanced the cardioprotective effects of Cre against ischemia-reperfusion injury.

PMID:40989754 | PMC:PMC12451010 | DOI:10.2147/JIR.S527105

Open Life Sci. 2025 Sep 8;20(1):20251163. doi: 10.1515/biol-2025-1163. eCollection 2025.

ABSTRACT

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. A key pathological feature of AF is atrial fibrosis, which promotes arrhythmogenic remodeling. While myocardial fibrosis has been widely observed in AF models, the underlying molecular mechanisms driving fibrotic progression remain incompletely understood. AF rats were modeled using acetylcholine, followed by treatment with different concentrations of dapagliflozin (DAPA) or positive control amiodarone. To elucidate the role of the high-mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) pathway in AF, lipopolysaccharide (LPS; an HMGB1/RAGE pathway activator) and FPS-ZM1 (a RAGE inhibitor) were employed. Cardiac function, myocardial fibrosis, and inflammation-related proteins were assessed using echocardiography, enzyme-linked immunosorbent assay, histological staining, Western blotting, and reverse transcription quantitative polymerase chain reaction. AF rats exhibited marked cardiac dysfunction, fibrosis, and increased expression of inflammatory markers. DAPA restored cardiac function, attenuating fibrosis and inflammation. LPS aggravated cardiac injury, while DAPA attenuated the damage, with the greatest protective effects observed in the LPS + DAPA + FPS-ZM1 group. DAPA attenuates atrial fibrosis and cardiac dysfunction in AF rats by inhibiting the HMGB1/RAGE pathway. This study suggests the potential of DAPA as a therapeutic option for AF.

PMID:40989585 | PMC:PMC12451426 | DOI:10.1515/biol-2025-1163

Circulation. 2025 Sep 24. doi: 10.1161/CIRCULATIONAHA.124.072312. Online ahead of print.

ABSTRACT

BACKGROUND: PYGM (muscle glycogen phosphorylase), the rate-limiting enzyme in glycogenolysis, plays an indispensable role in maintaining cardiac energy metabolism. However, the role of PYGM in the pathogenesis of myocardial infarction (MI) remains unclear.

METHODS: The expression profiles of PYGM in cardiac tissues and plasma samples from subjects with MI were assessed using immunoblotting. The role of PYGM in MI was determined by evaluating the effects of PYGM deficiency and its replenishment through adeno-associated virus-mediated PYGM expression in mice with MI.

RESULTS: We found that circulating PYGM levels and their cardiac contents were significantly decreased in patients with MI, which was associated with impaired cardiac function. Loss of PYGM significantly exacerbated MI-induced cardiac dysfunction and damage in mice, and replenishment of PYGM profoundly reversed these adverse effects. Mechanistically, PYGM enhanced glycogenolysis by activating glycolysis and the pentose phosphate pathway, thereby improving cardiac energy homeostasis and mitigating oxidative stress. In addition, PYGM improved MI-induced autophagic flux obstacles and alleviated MI-induced cardiac damage by suppressing the expression of Thbs1 (thrombospondin-1). Moreover, genetic deficiency or pharmacological blockage of autophagy attenuated the protective effects of PYGM against MI-induced cardiac injury, and cardiac-specific knockdown of Thbs1 substantially improved the adverse impact of MI on cardiac dysfunction and damage in PYGM-null mice.

CONCLUSIONS: PYGM safeguards against MI-induced myocardial injury by stimulating glycogenolysis and promoting autophagic flux, thus preserving myocardial energy homeostasis.

PMID:40988610 | DOI:10.1161/CIRCULATIONAHA.124.072312

Cardiovasc Diabetol. 2025 Sep 23;24(1):364. doi: 10.1186/s12933-025-02864-9.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) patients are at high risk for micro- and macrovascular complications, and cardiovascular (CV) events are a major cause of their increased risk of early death. Despite well-established treatment guidelines for the management of CV disease in T2DM, little is known about the real-world implementation of these guidelines.

OBJECTIVES: To characterize the real-life treatment patterns of T2DM patients with an incident CV comorbidity in Germany, to establish whether treatment is in line with respective national guidelines, and to assess guideline adherence with respect to the occurrence of serious clinical outcomes.

METHODS: This was a retrospective observational study using claims data from the WIG2 benchmark database including more than 4.5 million insured individuals. T2DM-prevalent patients with an incident CV comorbidity (ischemic stroke, myocardial infarction [MI], heart failure, or coronary artery disease) were identified between 2016 and 2018. Data on patient demographics and comorbidities were collected at baseline. During follow-up, data on treatment patterns and medical outcomes (all-cause mortality, modified 3P-MACE [composite endpoint of all-cause death or inpatient diagnosis of MI or stroke]) were captured. Guideline adherence was assessed using the medication possession ratio and was categorized as completely, partly or non-adherent.

RESULTS: Overall, 17,175 T2DM patients with a mean age of 71.1 years experiencing an incident CV comorbidity during the study period were identified. The most frequently prescribed CV treatments during follow-up were renin-angiotensin-aldosterone system inhibitors (83.9%), diuretics (72.6%) and beta-blocking agents (71.8%). Around 40% of the study population were treated completely adherent to the respective CV guidelines. These patients had a significantly higher chance of survival compared to patients not treated in line with the guidelines (90.8% vs. 82.6% survival within 12 months follow-up). Patients not treated according to CV guidelines had a higher mortality and 3P-MACE risk vs. patients completely adherent to guidelines (HR 1.93, 95% CI 1.65-2.25 and HR 1.49, 95% CI 1.31-1.69, respectively).

CONCLUSIONS: The results from this claims database study provide important insights into real-world management of CV comorbidities in T2DM patients in Germany and underline that inconsistent guideline adherence is a major unmet challenge to healthcare providers.

PMID:40988027 | PMC:PMC12455844 | DOI:10.1186/s12933-025-02864-9

Sci Rep. 2025 Sep 23;15(1):32664. doi: 10.1038/s41598-025-19853-3.

ABSTRACT

The therapeutic efficacy of anthracycline antibiotic, doxorubicin (DOX), is hampered due to cardiotoxicity. The objective of the study was to explore the counteraction of blueberry (BB) extract and Dexrazoxane (DEX) in Dox-induced cardiotoxicity in Wistar rats. Screening of BB extract as well as DEX for protection the myocardium from Dox-induced oxidative stress was performed on seven groups (8 rats each): Control (normal diet for 14 days and IP injection of normal saline (10 ml/kg) on the 11th day), DOX control (normal diet for 14 days with a single DOX injection of 18 mg/kg on the 11th day), BB extract control (80 mg/kg), DEX (180 mg/kg on the 11th day), BB + DOX (80 mg/kg BB extract for 14 days with DOX on the 11th day, 18 mg/kg), DEX + DOX (180 mg/kg DEX 30 min before 18 mg/kg DOX on the 11th day), and a combined group BB + DOX + DEX. A significant increase in serum biomarkers cTnT, NT-proBNP, MPO and cardiac MDA, TOP II, and a significant decrease in GSH and SOD contents were observed in the cardiotoxic (DOX control) group. All these parameters were reversed significantly in all treated groups in comparison to cardiotoxic groups. The cardiotoxic group showed significant upregulation of miR-140-5p expression and significant downregulation of Sirt2 and Nrf2 expression reversed in all treated groups except miR-140-5p which showed unsignificant difference. The best ameliorative effect was observed in the combined group. The histopathological assessment of myocardial damage provided supportive evidence for the biochemical results obtained. In conclusion, the BB extract (80.0 mg/kg) can attenuate the DOX-induced oxidative stress, and it has the potential to be developed as an adjunct against DOX-induced cardiotoxicity in cancer patients who undergo anthracycline chemotherapy.

PMID:40987807 | PMC:PMC12457682 | DOI:10.1038/s41598-025-19853-3

Basic Res Cardiol. 2025 Sep 23. doi: 10.1007/s00395-025-01140-x. Online ahead of print.

ABSTRACT

Cardiovascular diseases (CVD) include a wide range of disorders affecting the heart and blood vessels, many of which are associated with atherosclerosis. Atherosclerosis is the main underlying cause of CVDs and represents a chronic inflammatory disease of the large arteries involving the build-up of plaques within the arterial wall. B cells play a dual role in CVD, particularly in the context of atherosclerosis, by producing antibodies and secreting cytokines that modulate inflammation. Depending on their subtype (B1 vs. B2 cells) and the specific context, B cells can have both protective and harmful effects on the cardiovascular system. B1 cells, which arise predominantly during fetal development, are found in body cavities, such as the perivascular adipose tissue (PVAT) and peritoneum. Guided by CXCL13 and CCR6, they migrate to sites, where they produce IgM and IgG3, contributing to immune regulation and pathogen defense. In contrast, B2 cells-central players in adaptive immunity-originate in the bone marrow and mature in secondary lymphoid organs. Within this subset, marginal-zone (MZ) B cells provide rapid, low-affinity IgM responses to blood-borne antigens, while follicular (FO) B cells mediate high-affinity, T-cell-dependent antibody production. For all of the latter chemokine-guided migration is essential for B-cell function, from immune surveillance to antibody secretion. Receptors such as CXCR4, CXCR5, and ACKR3 not only direct B-cell trafficking but also influence their phenotype in cardiovascular disease. Understanding how these chemokine-receptor interactions shape B-cell-mediated immunity in CVD may allow for developing targeted therapies for atherosclerosis, myocardial infarction, and stroke.

PMID:40986007 | DOI:10.1007/s00395-025-01140-x

Cureus. 2025 Aug 22;17(8):e90748. doi: 10.7759/cureus.90748. eCollection 2025 Aug.

ABSTRACT

Cardiac procedures carry a higher perioperative risk than other operations for major adverse cardiovascular events and kidney injury, especially since patients with multiple comorbidities have been accepted as candidates for undergoing surgical treatment. Dexmedetomidine (DEX) is an alpha-2 agonist and has been widely used as an adjuvant anesthetic in clinical anesthesia for many different types of operations, including cardiac surgery. While it can be associated with bradycardia as well as hypotension in hypovolemic patients, DEX has been shown to reduce surgical complications like atrial fibrillation (Afib) and acute kidney injury (AKI), and is associated with an improved survival rate. In this review, we discuss the effect of using perioperative DEX on hemodynamics, arrhythmia, AKI, cognitive function, and surgical outcome in patients undergoing cardiac surgery both with and without cardiopulmonary bypass (CPB), and we review the mechanisms.

PMID:40984901 | PMC:PMC12450391 | DOI:10.7759/cureus.90748