Protección miocárdica

Sci Rep. 2025 Jul 1;15(1):20725. doi: 10.1038/s41598-025-07576-4.

ABSTRACT

Doxorubicin (DOX) is an effective anticancer drug, but its clinical application is limited due to its severe adverse effects on multiple organs and tissues, particularly cardiotoxicity. Studies suggest that metformin and Coenzyme Q10 (CoQ10) may help reduce DOX-induced cardiotoxicity. This study investigated the individual and combined effects of metformin and CoQ10 on DOX-induced cardiotoxicity in rats. 36 male Wistar rats were divided into six groups consisting of N_C, C_Dox (25 mg/kg DOX), C_(Met + Q10) (200 mg/kg metformin + 10 mg/kg CoQ10), T_Met (200 mg/kg metformin + 25 mg/kg DOX), T_Q10 (10 mg/kg CoQ10 + 25 mg/kg DOX), and T_(Met + Q10) (200 mg/kg metformin + 10 mg/kg CoQ10 + 25 mg/kg DOX). DOX administration significantly elevated serum CK-MB, LDH (P < 0.05), and tissue MDA (P < 0.001). It also significantly decreased TAC, CAT, GPx (P < 0.001), and SOD (P < 0.01) in heart tissues. Treatment with metformin and CoQ10 significantly restored the biochemical parameters both in the serum and tissue samples and ameliorated the histopathological damage caused by DOX. In conclusion, the combination of metformin and CoQ10 exerted antioxidant and cardioprotective effects against DOX-induced cardiotoxicity.

PMID:40596564 | PMC:PMC12214982 | DOI:10.1038/s41598-025-07576-4

Sci Rep. 2025 Jul 1;15(1):20859. doi: 10.1038/s41598-025-08720-w.

ABSTRACT

Myocardial infarction is a leading cause of death and morbidity in individuals with cardiovascular diseases. Natural antioxidants, such as those found in green tea leaves, are beneficial in preventing these diseases. This study evaluated the protective effects of green tea leaves powder against isoprenaline (ISO)-induced myocardial infarction in rats. Four groups of male Long Evans rats were used: Control, Control + green tea leaves powder, ISO, and ISO + green tea leaves powder. Organ and blood plasma samples were collected to measure oxidative stress biomarkers, biochemical parameters, and gene expressions. Furthermore, tissue sections were prepared and stained histologically. ISO-induced rats showed decreased cellular antioxidants (catalase activity and glutathione concentration) and elevated oxidative stress markers. Notable inflammatory cell infiltration and fibrosis were observed in the heart and kidneys of ISO-induced rats. Supplementation with green tea leaves powder significantly restored catalase activity and glutathione concentration (p < 0.05) in plasma and tissues. It also considerably reduced lipid peroxidation, nitric oxide, and advanced oxidation protein products (p < 0.05) in ISO-administered rats. Furthermore, green tea leaves powder supplementation halted inflammatory gene expression (p < 0.05), restored antioxidant genes (p < 0.05) such as Nrf-2-HO-1, and prevented cardiac fibrosis in ISO-administered rats. Green tea leaves powder supplementation may reduce oxidative stress, inflammation, and fibrosis in ISO-administered rats, potentially through the Nrf-2-HO-1-mediated restoration of antioxidant enzymes and prevention of heart inflammation.

PMID:40596364 | DOI:10.1038/s41598-025-08720-w

Sci Rep. 2025 Jul 1;15(1):22067. doi: 10.1038/s41598-025-03419-4.

ABSTRACT

Doxorubicin (DOX) is an anthracycline class of chemotherapy drug, the application of which is limited due to its cardiotoxic effects. Recombinant Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), is a serine protease pivotal in lipid metabolism and has a profound correlation with the onset of cardiovascular diseases. This study uncovers a connection between PCSK9 and DOX-induced cardiotoxicity (DIC). This research found that injection of DOX in mice caused cardiac toxicity. DOX treatment up-regulated the expression of PCSK9 protein in myocardial tissue. Evolocumab (PCSK9 inhibitors) improved cardiac function, myocardial injury, and fibrosis in DOX-treated mice, indicating a protective effect against DIC. The mechanism involved modulation of cardiomyocyte apoptosis and regulation of apoptosis-related proteins, including Bax/Bcl-2 ratio and Cleaved Caspase-3/Pro Caspase-3 ratio. DOX exhibited concentration- and time-dependent cytotoxic effects on H9C2 cardiomyocytes, promoting apoptosis. PCSK9 nuclear aggregation occurred in H9C2 cardiomyocytes after DOX treatment, and PCSK9 interacted with the Importin subunit beta-1 (KPNB1) protein. Interference with PCSK9 up-regulated KPNB1 expression, affecting apoptosis-related proteins and improving DOX-induced H9C2 cardiomyocyte apoptosis. In short, the elucidation of this mechanism is helpful involve that PCSK9 inhibitor may be a potential drug for improving DIC.

PMID:40593844 | PMC:PMC12215775 | DOI:10.1038/s41598-025-03419-4

Nat Commun. 2025 Jul 1;16(1):5927. doi: 10.1038/s41467-025-61028-1.

ABSTRACT

Cardiac hypertrophy leads to ventricular dysfunction and heart failure. Deubiquitinating enzymes are responsible for preserving the substrate protein stability and are essential to myocardial hypertrophy. In this study, we aimed to explore the role and regulatory mechanism of a cardiomyocyte-derived deubiquitinating enzyme, USP13, in cardiac hypertrophy. Here we show that USP13 was increased in hypertrophic myocardium and was mainly distributed in cardiomyocytes. Cardiomyocyte-specific Usp13 knockout aggravated TAC or Ang II-induced myocardial hypertrophy and dysfunction in male mice. Correspondingly, USP13 overexpression by AAV9 in hearts exerted a therapeutic impact on cardiac hypertrophy in male mice. Mechanistically, we identified STAT1 as a substrate of USP13 through interactome analysis. USP13 deubiquitinated STAT1, thereby reducing its degradation. Subsequently, USP13 promoted the STAT1-targeted Nppb gene transcription and enhanced mitochondrial function in cardiomyocytes. This study illustrated a beneficial effect of USP13 in hypertrophic cardiomyocytes and identified a cardiomyocyte-specific USP13-STAT1 axis in regulating cardiac hypertrophy.

PMID:40593642 | PMC:PMC12217623 | DOI:10.1038/s41467-025-61028-1

Sci Rep. 2025 Jul 1;15(1):22207. doi: 10.1038/s41598-025-06772-6.

ABSTRACT

Homocysteine can cause damage to cardiomyocytes. However, Mitophagy is essential for preserving homeostasis in cardiomyocytes. So, we focused on investigating the impact of homocysteine on cardiomyocyte mitophagy and cardiac hypertrophy through the β-catenin/FUNDC1 pathway. Mice were administered water containing homocysteine (1.8 g/L) to induce hyperhomocysteinemia for 4 weeks. The overexpression of specific genes, including β-catenin and FUNDC1, were performed by gene delivery mediated with adeno-associated virus. In vitro, cardiomyocytes were exposed to homocysteine (1 mmol/L) and then transfected with plasmids to overexpress β-catenin and FUNDC1, respectively. The duration of cell experiments was 48 h. Western blotting was employed to assess the expression levels of β-catenin, active β-catenin, FUNDC1, LC3, p62, α-actin, and β-MHC. Immunohistochemistry and immunofluorescence techniques were applied to measure β-catenin and FUNDC1 in cardiomyocytes. Cell viability was assessed using a CCK-8 assay kit, and mitophagy was observed under transmission electron microscopy. The interaction between β-catenin protein and the promoter of the FUNDC1 gene was examined using ChIP assay and dual-luciferase reporter gene assay. Homocysteine inhibited β-catenin signaling and the FUNDC1-mediated mitophagy in the cardiomyocytes, simultaneously promoting cardiac hypertrophy in vitro and in vivo. Elevated β-catenin signaling promoted FUNDC1 expression, then restored the normal level of mitophagy, and consequently inhibited homocysteine-induced cardiac hypertrophy. Similarly, overexpression of FUNDC1 restored mitophagy and protected cardiomyocytes from hypertrophy. In addition, FUNDC1 served as a target gene of β-catenin. In summary, homocysteine induces cardiomyocyte hypertrophy by inhibiting β-catenin signaling and suppressing FUNDC1-mediated mitophagy.

PMID:40593088 | PMC:PMC12214670 | DOI:10.1038/s41598-025-06772-6

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 1. doi: 10.1007/s00210-025-04354-x. Online ahead of print.

ABSTRACT

Sepsis-induced acute myocardial injury is a major cause of morbidity and mortality, characterized by inflammation, apoptosis, and impaired cardiomyocyte survival. Lipopolysaccharide (LPS)-induced cardiac injury models are commonly used to mimic sepsis and study its pathophysiological mechanisms. In this study, we investigated the protective effects of Eupatilin, a flavonoid compound derived from Artemisia argyi, on LPS-induced cardiac injury in rats and H9c2 cardiomyocyte cells. Our results show that Eupatilin significantly attenuated LPS-induced injury, as evidenced by increased cell viability, reduced inflammatory cytokine release, and decreased apoptosis. Mechanistically, we found that Eupatilin reduced the ubiquitination of Mcl-1, thereby promoting its stability and inhibiting apoptosis. Additionally, Eupatilin activated the PI3K/Akt signaling pathway, which led to the phosphorylation of Foxo3a, resulting in the retention of Foxo3a in the cytoplasm and the inhibition of apoptosis. These findings suggest that Eupatilin exerts protective effects against sepsis-induced myocardial injury by modulating Mcl-1 ubiquitination and activating the PI3K/Akt/Foxo3a pathway. Our study provides novel insights into the potential therapeutic application of Eupatilin in the treatment of sepsis-induced acute myocardial injury.

PMID:40590921 | DOI:10.1007/s00210-025-04354-x

Front Cardiovasc Med. 2025 Jun 16;12:1581056. doi: 10.3389/fcvm.2025.1581056. eCollection 2025.

ABSTRACT

INTRODUCTION: Calcitonin gene-related peptide (CGRP), particularly its alpha isoform, might play a role in restoring physiological cardiovascular functioning. While its involvement in acute myocardial infarction (AMI) pathophysiology has been suggested, human data remain scarce. This study analyzed circulating alpha-CGRP levels during AMI, comparing them to healthy controls (HC) and post-AMI resolution levels.

METHODS: A total of 26 AMI patients and 26 age- and sex-matched HC were recruited. Blood samples were collected from patients within four hours of AMI onset and, when possible, six months post-event. Alpha-CGRP serum concentrations were measured using a validated ELISA assay.

RESULTS: Alpha-CGRP levels were significantly higher in AMI patients at admission (mean ± SD: 96.0 ± 77.4 pg/ml) compared to HC (42.0 ± 25.8 pg/ml, p < 0.0001), with an average increase of 129%. Among nine patients available for follow-up, levels normalized to the HC range (45.1 ± 26.7 pg/ml, p = 0.011). Patients with poor outcomes had numerically lower alpha-CGRP levels (72.6 ± 37.2 pg/ml) than those with a satisfactory resolution (100.3 ± 82.5 70.6 pg/ml; p = 0.241).

DISCUSSION: Alpha-CGRP is acutely elevated during AMI, likely as a compensatory vasodilator response to ischemia. Its post-AMI normalization suggests a transient protective mechanism. Further research is needed to explore its role in AMI-related pathophysiology and usefulness as a therapeutic agent.

PMID:40589453 | PMC:PMC12206774 | DOI:10.3389/fcvm.2025.1581056

Acta Pharmacol Sin. 2025 Jun 30. doi: 10.1038/s41401-025-01604-9. Online ahead of print.

ABSTRACT

Circular RNAs (circRNAs) are a distinct class of endogenous RNAs characterized by their covalently closed circular structure. CircRNAs play crucial regulatory roles in various biological processes and pathogenesis. In this study we investigated the role of circRNAs in cardiomyocyte pyroptosis and underlying mechanisms. Ischemia/reperfusion (I/R)-induced myocardial injury was induced in mice by ligation of the left anterior descending coronary artery (LAD). Neonatal mouse cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) assault. By using circRNA microarray, we found that the expression levels of a pyroptosis-related circRNA (designated PYRCR) were markedly decreased in H/R-exposed cardiomyocytes and I/R-injured mouse hearts. Overexpression of PYRCR inhibited cardiomyocyte pyroptosis, attenuated I/R-induced myocardial infarction and ameliorated cardiac function in mice. By RNA pull-down assays coupled with MS analysis followed by molecular validation, we identified developmental regulated GTP-binding protein 2 (DRG2) as the direct downstream target of PYRCR. Cardiac-specific DRG2 knockout mice displayed attenuated pyroptosis and enhanced cardiac function following I/R injury compared to DRG2fl/fl controls. DRG2 directly bound to dynamin-related protein 1 (Drp1), the master regulator of mitochondrial fission, and enhanced its protein stability and expression. Importantly, PYRCR competitively disrupted the DRG2-Drp1 interaction, thereby suppressing DRG2-mediated Drp1 expression and subsequently reducing mitochondrial fission, cardiomyocyte pyroptosis, and myocardial damage. In conclusion, we demonstrate that PYRCR, a novel pyroptosis-related circRNA, protects against I/R-induced myocardial injury through the DRG2-mediated modulation of Drp1 activity, offering promising new therapeutic strategies for preventing cardiac damage mediated by cardiomyocyte pyroptosis.

PMID:40588510 | DOI:10.1038/s41401-025-01604-9

Theranostics. 2025 Jun 9;15(14):6737-6752. doi: 10.7150/thno.110162. eCollection 2025.

ABSTRACT

Rationale: Myocardial ischemia reperfusion (I/R) injury is a major cause of adverse outcomes following revascularization therapy. Although alterations in metabolic activities during reperfusion have been implicated, the molecular mechanisms underlying the pathogenesis of I/R injury remain elusive. Metaxin 2 (MTX2), initially identified as a core component of protein import complexes, has recently been characterized in diverse cellular functions. Nevertheless, its involvement in myocardial I/R injury has yet to be fully elucidated. In this study, we aim to evaluate the role and the underlying mechanism of MTX2 in I/R injury. Methods: The myocardial I/R model was established, and the protein levels of MTX2 were determined at different time points following coronary occlusion. Loss-of-function and gain-of-function strategies were applied via genetic ablation or intra-myocardial adenovirus injection to ascertain the role of MTX2 in myocardial I/R injury. RNA sequencing, seahorse metabolic analysis, and mass spectrometry were conducted to uncover the underlying molecular mechanisms. Results: We observed that the expression of MTX2 was significantly decreased in I/R hearts. Tamoxifen-induced cardiomyocyte-specific deletion of Mtx2 led to aggravated myocardial I/R injury, resulting in impaired cardiac oxidative phosphorylation and glycolysis. Mechanistically, dimeric PKM2, a less active pyruvate kinase form compared with tetrameric PKM2, was found to be dramatically accumulated in Mtx2 deficiency mice after myocardial I/R surgery. The TOM37 domain of MTX2 interacted directly with PKM2 to promote PKM2 tetramerization, thereby modulating glucose metabolic flux. Pharmacological activation of PKM2 by a small-molecule PKM2 activator, TEPP-46, rescued the metabolic and functional outcomes of I/R in Mtx2 deficiency mice. Conclusions: Our results identified, for the first time, a cardioprotective role of MTX2 in modulating cardiac glucose metabolism by facilitating PKM2 tetramerization. Targeting metabolic homeostasis by restoring MTX2 might be a promising therapeutic strategy to mitigate myocardial I/R injury.

PMID:40585998 | PMC:PMC12203670 | DOI:10.7150/thno.110162

Theranostics. 2025 Jun 9;15(14):6753-6767. doi: 10.7150/thno.104124. eCollection 2025.

ABSTRACT

Rationale: Cardiomyocyte apoptosis critically contributes to ischemic heart failure (IHF) progression. While the endosome-lysosome system governs cellular homeostasis, the functional significance of its master regulator RAB7 in cardiac pathophysiology remains unexplored. Methods: Using myocardial infarction (MI) models via left anterior descending coronary artery ligation in cardiomyocyte-specific RAB7 knockout mice and adeno-associated virus-mediated RAB7 overexpression models, we assessed cardiac function and adverse remodeling through echocardiography and pathophysiological assessment. Mitophagy flux was quantified using mt-Keima mice and confocal imaging. Molecular mechanisms were dissected through immunoprecipitation coupled with mass spectrometry (IP-MS) analysis and molecular experiment validation. Results: RAB7 expression decreased in ischemic myocardium. Cardiomyocyte-specific RAB7 ablation exacerbated while RAB7 overexpression attenuated post-MI cardiac dysfunction and maladaptive remodeling. RAB7 enhanced mitophagic clearance of damaged mitochondria, reducing cardiomyocyte apoptosis under ischemic stress both in vitro and in vivo. Mechanistically, TUFM, a mitochondrial translation elongation factor, was identified as a novel effector of RAB7. RAB7 facilitated the recruitment of TUFM and LC3 to damaged mitochondria, thereby enhancing mitophagy. TUFM knockdown significantly diminished the protective effects of RAB7 on mitophagy and cardiomyocyte survival. Finally, administration of ML-098, a chemical RAB7 activator, promoted mitophagy and mitigated IHF progression in mice. Conclusion: We identify RAB7 as a novel coordinator of cardioprotective mitophagy through TUFM-mediated machinery assembly. The RAB7-TUFM axis represents a therapeutic target for IHF that warrants further clinical evaluation.

PMID:40585970 | PMC:PMC12203679 | DOI:10.7150/thno.104124

Geriatr Orthop Surg Rehabil. 2025 Jun 28;16:21514593251353114. doi: 10.1177/21514593251353114. eCollection 2025.

ABSTRACT

INTRODUCTION: Surgical fixation of hip fractures in older adults is associated with significant morbidity and mortality. We investigated whether regional anesthesia, which excluded epidural, spinal, or combined epidural-spinal, was associated with lower postoperative complication rates compared to general or spinal anesthesia in patients aged 50 years and older undergoing hip fracture surgery.

METHODS: A retrospective analysis was conducted using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Targeted Hip Fracture dataset from January 1, 2016, to December 31, 2022. Propensity score matching was used to compare regional anesthesia with general and spinal anesthesia. Given the NSQIP database excludes epidural, spinal, and combined epidural-spinal anesthesia from the regional classification, it was presumed that the remaining regional anesthesia patients received a peripheral nerve block. The primary outcome measure was a 30-day composite of death, myocardial infarction, or stroke.

RESULTS: The study analyzed 54,623 patients, from which 323 received regional anesthesia. These were separately matched with 323 cases of general anesthesia and 323 cases of spinal anesthesia. Regional anesthesia was associated with a lower incidence of the primary composite outcome compared to both general anesthesia (3% vs 7%, risk ratio 0.3, 95% CI: 0.2 to 0.6, P < 0.001) and spinal anesthesia (3% vs 7%, risk ratio 0.5, 95% CI: 0.3 to 0.9, P = 0.01). A subgroup effect was detected, with high-risk patients (ASA IV-V) experiencing the greatest protective benefit from regional anesthesia.

CONCLUSIONS: Regional anesthesia techniques, excluding epidural, spinal, or combined epidural-spinal techniques, were associated with lower rates of major postoperative complications in older adults undergoing hip fracture surgery compared to general or spinal anesthesia. This benefit was more pronounced in high-risk patients. Our findings suggest that regional anesthesia, most likely administered via a peripheral nerve block, may offer benefits beyond pain control in this population, potentially improving postoperative outcomes.

PMID:40585866 | PMC:PMC12206264 | DOI:10.1177/21514593251353114

Circulation. 2025 Jun 30. doi: 10.1161/CIRCULATIONAHA.124.069737. Online ahead of print.

ABSTRACT

BACKGROUND: Pathological cardiac remodeling after myocardial infarction (MI) is a leading cause of heart failure and sudden death. The detailed mechanisms underlying the transition to heart failure after MI are not fully understood. Disruptions in the endoplasmic reticulum (ER)-mitochondria connectivity, along with mitochondrial dysfunction, are substantial contributors to this remodeling process. In this study, we aimed to explore the impact of mitochondrial tumor suppressor 1A (Mtus1A) on cardiac remodeling subsequent to MI and elucidate its regulatory role in ER-mitochondria interactions.

METHODS: Single-nucleus RNA sequencing analysis was performed to delineate the expression patterns of Mtus1 in human cardiomyocytes under ischemic stress. MI models were induced in mice by left coronary artery ligation and replicated in vitro using primary neonatal rat ventricular myocytes exposed to oxygen glucose deprivation. Cardiac-specific deletion of Mtus1 was achieved by crossing floxed Mtus1 mice with the Myh6-MerCreMer mice. The impact of Mtus1A, a mitochondrial isoform of Mtus1, on cardiac function and the molecular mechanisms were investigated in both in vivo and in vitro settings. Mitochondria-associated ER membranes coupling levels were evaluated by transmission electron microscopy and live-cell imaging. Protein interactions involving Mtus1A were explored through immunoprecipitation-mass spectrometry, coimmunoprecipitation, and proximity ligation assay. The roles of Mtus1A and Fbxo7 (F-box protein 7) were validated in a murine MI model using adeno-associated virus serotype 9 (AAV9).

RESULTS: Bioinformatics analysis revealed a significant downregulation of Mtus1 expression in human cardiomyocytes under ischemic conditions, indicating its potential role in stress response. The predominant isoform in murine cardiomyocytes, Mtus1A, showed reduced expression in the left ventricle of mice after MI, which is consistent with the decreased levels of its orthologs in heart tissues from patients with MI. Cardiac-specific knockout of Mtus1 in mice exacerbated cardiac dysfunction after MI. Both in vitro and in vivo studies demonstrated the vital role of Mtus1A in modulating mitochondria-associated ER membranes coupling and preserving mitochondrial function. Mechanistically, Mtus1A functions as a scaffold protein that maintains the formation of inositol 1,4,5-trisphosphate receptor 1 (IP3R1)-glucose-regulated protein 75 (Grp75)-voltage-dependent anion channel 1 (VDAC1) complex through its amino acid sequence 189-219. In addition, Mtus1A protein is stabilized by K6-linked ubiquitination through the E3 ubiquitin ligase Fbxo7. Mtus1A overexpression in mice mitigated MI-induced cardiac dysfunction and remodeling by maintaining ER-mitochondria connectivity.

CONCLUSIONS: Our study demonstrates that Mtus1A is crucial for modulating MI-induced cardiac remodeling by preserving ER-mitochondria communication and ameliorating mitochondrial function in cardiomyocytes. Mtus1A may serve as a potential therapeutic target for treating heart failure after MI.

PMID:40583767 | DOI:10.1161/CIRCULATIONAHA.124.069737

J Control Release. 2025 Jun 27:113989. doi: 10.1016/j.jconrel.2025.113989. Online ahead of print.

ABSTRACT

Extracellular vesicles (EVs) derived from stem cells have shown therapeutic benefits in myocardial injury. However, the challenges in their large-scale production and elusive molecular mechanisms underlying their therapeutic effects have been hindering their clinical translation. Here, in a mouse model of myocardial ischemia-reperfusion, EVs isolated from human adipose tissue and EV-like nanovesicles fabricated with adipose stem cells (ADSCs) via a membrane extrusion approach, termed ADSC-derived nanovesicles (ADSC-CDNs), exhibited comparable cardioprotective effects, validating this EV-mimetic strategy. CDNs generated from the human monocytic cell line U937 similarly conferred protection, whereas those from HEK293 cells did not, highlighting the importance of cell source for therapeutic efficacy. microRNA profiling identified miR-24-3p as a predominant therapeutic cargo in ADSC EVs and ADSC-CDNs. This microRNA upregulates the cytoprotective transcription factor Nrf2, thereby suppressing cardiomyocyte apoptosis. Functional assays also confirmed that miR-24-3p was a key component mediating the cardioprotective effects of those nanovesicles. Importantly, this study introduces a cell-source-dependent, scalable, and high-yield production platform for ADSC-CDNs that preserves molecular cargo profile of the parent cells, ensuring consistent therapeutic content. This EV-mimetic platform is technically feasible and clinically translatable, demonstrating reproducible efficacy in both acute injury and post-infarction recovery phases. Taken together, the defined microRNA cargo and the robust vesicle production strategy highlight the translational potential of ADSC-CDNs as an off-the-shelf cardioprotective therapy.

PMID:40582645 | DOI:10.1016/j.jconrel.2025.113989

Biochem Biophys Res Commun. 2025 Jun 25;777:152235. doi: 10.1016/j.bbrc.2025.152235. Online ahead of print.

ABSTRACT

BACKGROUND: Environmental pollution, particularly noise exposure, may contribute to the development and progression of cardiovascular disorders by triggering oxidative stress and inflammatory pathways. This study evaluated the protective effects of benfotiamine (BFT) supplementation and moderate-intensity continuous training (MICT), alone or in combination, against noise-induced cardiac damage in male mice.

METHODS AND RESULTS: Eight-week-old mice (n = 8/group) were divided into six groups: control, noise-exposed (Noise) subjected to 100 dB (dB), noise + moderate-intensity continuous exercise training (MICT), noise + BFT group (200 mg/kg/day), noise + MICT + BFT, and noise + N-acetylcysteine (NAC) groups. Noise exposure and other treatments were administered over four weeks. Histopathological changes, oxidative stress parameters, and the gene expression of inflammatory markers were evaluated. Noise exposure markedly increased cardiac ROS, NO, MDA, and protein carbonyl content, while significantly decreasing GSH and FRAP levels (all p < 0.001 vs. control). Treatment with BFT or MICT partially restored redox balance, whereas combined BFT + MICT treatment produced more pronounced improvements (e.g.

, MDA: 9.91 ± 4.45; GSH: 101.2 ± 20.1 μM). Inflammatory markers IL-6, TNF-α, IL-1β, and NF-κB were upregulated by noise and significantly attenuated by all interventions, with the greatest reduction observed in the combined group. Histological analysis confirmed that the combined therapy more effectively preserved myocardial architecture compared to monotherapies.

CONCLUSION: Our findings suggest that BFT's antioxidant and anti-inflammatory properties, in combination with MICT as a non-pharmacological approach, may protect against noise-induced cardiovascular problems. BFT and MICT mitigate noise-induced cardiac injury via antioxidant and anti-inflammatory mechanisms, with additive benefits evident in the combined treatment group.

PMID:40582321 | DOI:10.1016/j.bbrc.2025.152235

Med Sci Monit. 2025 Jun 16;31:e947831. doi: 10.12659/MSM.947831.

ABSTRACT

BACKGROUND Acute coronary syndrome (ACS) is a prevalent cardiovascular disease with persistent risks of myocardial under-perfusion and adverse events after percutaneous coronary intervention (PCI). The combination of tirofiban and cilostazol has shown potential efficacy, but clinical validation remains limited. This study evaluated the effects of tirofiban combined with cilostazol on cardiac function recovery and prognosis in elderly ACS patients after PCI. MATERIAL AND METHODS This study included 80 elderly ACS patients treated between April 2020 and April 2022. Patients were assigned to the control group (n=40), receiving aspirin and clopidogrel, or the observation group (n=40), receiving tirofiban and cilostazol after PCI. We assessed cardiac function, myocardial markers, serum inflammatory factors, platelet aggregation rate, platelet count (PLT), quality-of-life scores, and the incidence of major adverse cardiovascular events (MACE). RESULTS The treatment effectiveness was 97.50% in the observation group versus 80.00% in the control group. One month after PCI, the observation group had lower left ventricular end-diastolic diameter and left ventricular end-systolic diameter and higher left ventricular ejection fraction. Inflammatory markers (IL-6, hs-CRP, TNF-alpha), platelet aggregation rate, and PLT levels were significantly decreased. Myocardial markers (CK-MB, hs-cTnT) were elevated at 24 hours but improved by 1 month. Quality-of-life scores improved significantly, and MACE incidence was lower in the observation group. CONCLUSIONS Tirofiban combined with cilostazol enhances cardiac function, reduces inflammation, platelet aggregation, and myocardial injury, and improves prognosis in elderly ACS patients after PCI.

PMID:40581838 | PMC:PMC12180374 | DOI:10.12659/MSM.947831

Lancet Glob Health. 2025 Jul;13(7):e1191-e1202. doi: 10.1016/S2214-109X(25)00109-3.

ABSTRACT

BACKGROUND: Stroke, ischaemic heart disease, and dementia share risk factors and influence one another, substantially affecting brain health. Limited health-care resources in Africa might exacerbate the burden of these diseases, with serious brain health consequences. We analysed trends from 1990 to 2021 to inform optimised prevention strategies.

METHODS: Using The Global Burden of Diseases, Injuries, and Risk Factors Study 2021 data, we assessed the burden of these conditions, measured by disability-adjusted life-years (DALYs) lost attributed to 12 risk factors, and their changes from 1990 to 2021. Bayesian modelling generated means and 95% uncertainty intervals (UIs) based on the 2·5th and 97·5th percentiles of 500 posterior distribution draws.

FINDINGS: In Africa in 2021, 17·3 (95% UI 15·5-19·2) million DALYs were lost due to strokes, 17·6 (15·5-19·6) million were lost due to ischaemic heart diseases, and 1·8 (0·8-4·0) million were lost due to dementia. New and prevalent cases doubled from 1990 to 2021, with two-thirds of DALYs occurring before age 70 years. Among five continents, Africa had the highest age-standardised DALY rates per 100 000 population for stroke (2628·1 [2367·4-2893·0]) and ischaemic heart disease (2743·5 [2451·8-3033·6]), and the lowest for dementia (423·4 [190·6-934·6]). Regionally, central and southern Africa showed higher stroke DALY rates, northern Africa had the highest rates for ischaemic heart disease, and central and northern Africa had the highest rates for dementia. Among 12 modifiable risk factors, high systolic blood pressure, unhealthy diet, and air pollution contributed most to DALYs. Stroke DALYs rose prominently due to high BMI, high fasting plasma glucose, high LDL cholesterol, low physical activity, and high systolic blood pressure.

INTERPRETATION: Africa faces substantial challenges from stroke, heart disease, and dementia, including the highest DALY rates globally, with worsening trends over the past three decades, including younger ages of onset. These patterns, coupled with limited health resources, necessitate urgent and targeted strategies to protect, preserve, and promote brain health in Africa.

FUNDING: Weston Family Foundation.

PMID:40580987 | DOI:10.1016/S2214-109X(25)00109-3

Biomed Pharmacother. 2025 Jun 27;189:118296. doi: 10.1016/j.biopha.2025.118296. Online ahead of print.

ABSTRACT

Lipid peroxidation and ferroptosis are critically for the development of cardiac ischaemia-reperfusion (I/R) injury. The proteasome complex is crucial for regulating inflammation and cardiac I/R injury. Proteasome-activating peptide 1 (PAP1) is an activator of the proteasome β5i subunit, but its role in cardiac I/R injury remains unknown. Our results indicate that the administration of PAP1 highly enhanced the expression and activity of the β5i in cardiac tissues possibly by inhibiting of STAT3. Moreover, compared with vehicle control, administration of PAP1 in wild-type mice greatly reversed the I/R-induced decline in myocardial contractility and increases in myocardial infarction, fibrosis, myocyte apoptosis, ROS production and inflammatory response. RNA sequencing revealed that PAP1 mainly affected the genes that were associated with heart contraction, ferroptosis, apoptosis, ROS production and p53. Furthermore, PAP1 clearly decreased the p53 protein and increased the protein levels of SLC7A11 and GPX4 both in mice and cultured cardiomyocytes. Conversely, these protective actions of PAP1 were significantly eliminated in the mice treated with the β5i inhibitor epoxomicin or in the cardiomyocytes transfected with shRNA-β5i but were enhanced by the inhibition of p53 with pifithrin-α. Mechanistically, PAP1 increased the β5i expression, which then bound to p53 and promoted its degradation, resulting in the upregulation of SLC7A11 and GPX4 proteins and the attenuation of oxidative stress and ferroptosis. In summary, our findings suggest that PAP1 can protect against myocardial I/R injury possibly via the β5i-p53-SLC7A11 axis and represent a novel drug candidate for the treating ischaemic heart injury.

PMID:40580875 | DOI:10.1016/j.biopha.2025.118296

Phytomedicine. 2025 Jun 16;145:156994. doi: 10.1016/j.phymed.2025.156994. Online ahead of print.

ABSTRACT

BACKGROUND: Tanshinone I (Tan I) is an essential active ingredient of the traditional cardiovascular medicine Salvia miltiorrhiza Bunge (S. miltiorrhiza). Although the protection of Tan I on cardiomyocyte has been reported, its anti-myocardial ischemia effects and mechanisms remain unknown.

PURPOSE: Systematic evaluation of the role of Tan I in reducing myocardial ischemia (MI) injury and elucidation of the underlying molecular mechanisms by which Tan I improves myocardial fibrosis and ventricular function in mouse MI models.

METHODS: In vivo and in vitro MI models were constructed to substantiate the anti-MI effects of Tan I. Through target fishing, molecular docking, and network pharmacology investigation, the effect mechanisms and potential target proteins of Tan I against MI were predicted further. Tandem mass tags (TMT)-based quantitative proteomics, transforming growth factor beta receptor I (TGFBR1)-overexpressing lentiviral vectors, molecular dynamics (MD) simulations, biolayer interferometry (BLI), cellular thermal shift assay (CETSA), TGFBR1 kinase activity, and drug affinity responsive target stability (DARTS) assay were subsequently used to validate the anti-MI-effect mechanisms and targets of Tan I.

RESULTS: Tan I can markedly increase the survival of oxidative stress cell models, improve intracellular environment, and inhibit the release of intracellular reactive oxygen species. Moreover, it can restore abnormal electrocardiograms, decrease myocardial infarction area, inhibit cardiac fibrosis, and reduce serum levels of key cardiac injury biomarkers in the MI mouse model. Mechanistically, Tan I considerably inhibited the phosphorylation modification levels of TGFBR1 and Smad2 and the aberrant expressions of Collagen I/III, α-smooth muscle actin, Bcl-2, and Bax proteins in MI mice. These findings were further verified in NIH-3T3 cells overexpressing TGFBR1 or activated by TGF-β1. MD simulations, CETSA, and DARTS showed that TGFBR1 binding to Tan I was relatively stable. In addition, BLI indicated that the equilibrium dissociation constant of Tan I binding TGFBR1 was 1.5 × 10-6 M. Based on the kinase activity assay, Tan I restrained TGFBR1 with a half-maximal inhibitory concentration of 739.6 nM.

CONCLUSION: This work reveals for the first time that Tan I can reduce MI injury and fibrosis by modulating the TGF-β signaling pathway via targeting of TGFBR1.

PMID:40580691 | DOI:10.1016/j.phymed.2025.156994

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 28. doi: 10.1007/s00210-025-04409-z. Online ahead of print.

ABSTRACT

PURPOSE: Cardiovascular diseases are one of the leading causes of death worldwide. Vitamin D (VITD) regulates cell proliferation, differentiation, apoptosis and angiogenesis. It boosts glutathione synthesis, reduces reactive oxygen species (ROS), protects tissues and exerts anti-inflammatory effects by lowering proinflammatory cytokines (IL-1β, IL-6, TNF-α) through VITD receptor activation. The aim of this study was to investigate the effects of VITD on liver tissue changes, oxidative stress and inflammation following myocardial infarction (MI) and ischemia/reperfusion (I/R) injury, focusing on its modulation of asprosin (ASP), spexin (SPX) and meteorin-like (METRNL) biomarkers to explore new therapeutic strategies.

METHODS: Rats were divided into four groups (n=7): Control (I), MI (II), VITD (III), and MI + VITD (IV). MI was induced with 200 mg/kg isoproterenol, and VITD (50 IU/day) was administered for 14 days as treatment.

RESULTS: Histopathologically; congestion, sinusoidal dilatation, necrotic hepatocytes and fibrosis, and immunohistochemically; ASP, SPX and METRNL immunoreactivity were examined in the liver tissues of rats. In the immunohistochemical examination of ASP, SPX and METRNL, the histoscore in the MI group was significantly higher compared to the control and VITD groups (p<0.001). The effect size of these differences was large.

CONCLUSION: ASP, SPX, and METRNL can be used as immunohistochemical biomarkers in order to demonstrate ischemia reperfusion injury in the liver of rats with MI. When the findings are evaluated, the application of VITD, a cytoprotective antioxidant, appears to play an effective role in preserving the biochemical and histological properties of hepatocytes. VITD is considered to contribute significantly to the histopathological and biochemical preservation of liver tissue.

PMID:40580311 | DOI:10.1007/s00210-025-04409-z

Proteomics. 2025 Jun;25(11-12):e00087. doi: 10.1002/pmic.202500087.

ABSTRACT

As space exploration becomes increasingly accessible, understanding the molecular and pathophysiological consequences of spaceflight on the human body becomes crucial. Space-induced modifications could disrupt multiple signaling pathways, with significant implications for the functional integrity of cardiovascular, nervous, and musculoskeletal systems, among others. In a recent study, Bourdakou et al. have focused on alterations in gene expression profiles linked to cardiovascular disease (CVD), using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) undergoing spaceflight and subsequent postflight conditions. Genes with known associations with CVD and nuclear factor erythroid 2-related factor 2 (NRF2) oxidative stress regulatory network have been identified to present consistent directional expression changes in both spaceflight and postflight. A computational drug repurposing analysis identified ten candidate agents with the potential to reverse observed transcriptomic modifications in spaceflight-exposed cardiomyocytes. These findings highlight the importance of molecular studies and emphasize the need for integrative, multi-omic research efforts to protect human health during and beyond spaceflight.

PMID:40579866 | DOI:10.1002/pmic.202500087