Protección miocárdica

PeerJ. 2025 Oct 3;13:e20145. doi: 10.7717/peerj.20145. eCollection 2025.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) significantly increases the risk of acute myocardial infarction (AMI). Polymorphisms in the ADIPOQ gene, which encodes the adiponectin hormone, are believed to influence cardiovascular disease risk. This study aims to evaluate the association between three ADIPOQ gene variants-rs266729, rs2241766, and rs1501299-and the risk of AMI in Vietnamese patients with T2DM.

METHODS: A case-control study was conducted from January 2023 to June 2024 at the University Medical Center, Ho Chi Minh City. The study included 275 T2DM patients with a history of AMI (case group) and 275 T2DM patients without AMI (control group). Participants were matched by age, gender, smoking status, and duration of T2DM to control for potential confounding factors. DNA was extracted from peripheral blood samples, and the three polymorphisms were genotyped using Sanger sequencing.

RESULTS: Significant associations were found between ADIPOQ gene polymorphisms and AMI risk. The G/G genotype of rs266729 and the T/T genotype of rs1501299 were associated with a reduced risk of AMI (OR = 0.45, 95% CI [0.23-0.89], p = 0.021; OR = 0.45, 95% CI [0.22-0.90], p = 0.025, respectively). In contrast, the T/G genotype of rs2241766 was significantly associated with an increased risk of AMI (OR = 2.07, 95% CI [1.44-2.97], p < 0.001).

CONCLUSION: This study suggests that rs266729 and rs1501299 may have protective effects, while rs2241766 may increase the risk of AMI in Vietnamese patients with T2DM. These findings highlight the importance of further research into adiponectin levels and long-term monitoring, and support the potential use of genetic variants in personalized cardiovascular risk management for patients with T2DM.

PMID:41059404 | PMC:PMC12499558 | DOI:10.7717/peerj.20145

Front Pharmacol. 2025 Sep 22;16:1625232. doi: 10.3389/fphar.2025.1625232. eCollection 2025.

ABSTRACT

Mitsugumin 53 (MG53), a member of the tripartite motif family proteins, is predominantly expressed in skeletal and cardiac muscles. Endogenous MG53 was first identified as a crucial component of the sarcolemmal membrane repair machinery. In cardiac muscles, MG53 prevented against ischemia/reperfusion-induced myocardial injury. Recent research has demonstrated that native MG53 is present in and performs significant functions within various non-striated muscle tissues, including lung epithelial cells, the inner cortex of the kidney, macrophages, aortic valves, corneal epithelial cells, as well as in the tear film and aqueous humor. These studies indicate a potential application of recombinant human MG53 (rhMG53) in various disease models. To date, an increasing number of studies have confirmed that rhMG53 exhibits broad protective effects in skeletal muscle injury, cardiovascular diseases, and other multiple-organ injuries. In this review, we clarify the therapeutic functions of rhMG53 and the molecular mechanisms involved in multiple organ injuries, emphasizing the development of rhMG53 protein as a potential therapeutic agent for treating a range of diseases.

PMID:41059189 | PMC:PMC12497760 | DOI:10.3389/fphar.2025.1625232

J Neuroendovasc Ther. 2025;19(1):2025-0092. doi: 10.5797/jnet.oa.2025-0092. Epub 2025 Oct 4.

ABSTRACT

OBJECTIVE: Carotid artery stenting (CAS) has been reported to be a safe and effective option for treating carotid atherosclerotic disease. However, reports and studies from resource-limited countries are scarce. The published data support the use of embolic protection devices (EPDs) to reduce periprocedural stroke. This study aimed to evaluate the outcomes of CAS procedures without EPDs in Yemen, one of the lowest-income countries.

METHODS: This is a retrospective cohort study regarding CAS for symptomatic carotid artery stenosis that was conducted at the stroke center of Borg Al-Atiba and American Modern Hospital during the period from March 2023 to March 2025. All patients with symptomatic carotid artery stenosis were included in the study. CAS procedures were performed by a single interventional neurologist. The primary outcomes included a 30-day periprocedural mortality, stroke, myocardial infarction, or arrhythmia. Any other complications were considered secondary outcomes.

RESULTS: A total of 62 patients (53 males) were included in this study, with a mean age of 60.2 ± 9.7 years. All patients had symptomatic carotid artery stenosis. The technical success rate was 100%. No perioperative cerebral infarctions were observed. One patient developed transient dysarthria, but diffusion-weighted-MRI was negative. Significant bradycardia occurred in 2 patients and responded immediately to atropine. Three patients developed mild local hematoma, and 1 patient had a femoral pseudoaneurysm. Closed-cell Carotid WALLSTENT (Boston Scientific, Marlborough, MA, USA) was used as a single stent in all patients.

CONCLUSION: CAS conducted by a trained interventional neurologist without EPDs demonstrates a low complication rate, and it is an effective and safe option in countries with limited resources.

PMID:41059090 | PMC:PMC12500383 | DOI:10.5797/jnet.oa.2025-0092

Nurs Res Pract. 2025 Sep 28;2025:7096059. doi: 10.1155/nrp/7096059. eCollection 2025.

ABSTRACT

Objective: This study aims to comprehend the current status of prehospital delay among patients with acute myocardial infarction. It analyzes the correlation between various factors and prehospital delay and explores the influencing factors. Methods: A cross-sectional survey was conducted. From February to June 2023, 260 AMI patients were selected by consecutive sampling from the study hospital in Yanji City, Jilin Province. General Data Questionnaire, Pain level Scale, Family Support Scale, Psychological distress scale, and Chinese version of the perceived impairment of medical decision-making scale were used. SPSS 28.0 and AMOS 28.0 were employed for t-test, chi-square test, Pearson correlation analysis, binary logistic regression analysis, and model construction. Results: The median prehospital delay time was 4.67 h. There were 174 patients with prehospital delay, accounting for 66.92%. The structural equation model indicated that the total effect values of prehospital delay influencing factors from strong to weak were pain level (-0.294), a perceptual disorder of medical decision-making (0.209), psychological distress (0.084), and family support (-0.068). Conclusions: Approximately two-thirds of patients experience a prehospital delay. Risk factors for prehospital delay include being female, lower family monthly income, lower education level, complications, symptom relief after taking medicine, lack of health care awareness, seeing a doctor alone, psychological distress, and perceptual disorder of medical decision-making. Protective factors are the pain level and family support. Patient or Public Contribution: No patient or public contribution. Reporting Method: The authors adhered to the EQUATOR network guidelines STROBE to report observational cross-sectional studies.

PMID:41058922 | PMC:PMC12497531 | DOI:10.1155/nrp/7096059

Cell Death Discov. 2025 Oct 7;11(1):453. doi: 10.1038/s41420-025-02725-0.

ABSTRACT

Recent studies found that treatment with an anti-T-cell immunoglobulin mucin-1 (TIM1) monoclonal antibody (RMT1-10) regulated immune responses by inducing regulatory B cells (Bregs). However, the role of these cells in myocardial ischemia-reperfusion injury (IRI) is unknown. This study aimed to investigate the protective effect of RMT1-10 on myocardial IRI and its potential mechanism. We established a myocardial IRI model, and Triphenyl tetrazolium chloride staining, Terminal deoxynucleotidyl transferase nick-end-labeling, hematoxylin and eosin, and transmission electron microscopy were performed to examine the myocardial infarction size, myocardial cell apoptosis, and cardiomyocyte morphology and structure. The data showed that RMT1-10 could alleviate myocardial IRI, increase the number of TIM1+Bregs and interleukin 10 (IL-10) secretion, and regulate the expression of inflammatory factors after myocardial IRI. However, treatment with RMT1-10 and Anti-CD20 abrogated the protective effect of RMT-10. In addition, RMT1-10 treatment inhibited T cells but significantly activated Tregs after IRI, while RMT1-10 combined with Anti-CD20 abolished this effect on Tregs. Furthermore, sequencing analysis showed marked expression changes among genes related to several classical signaling pathways in response to RMT1-10. Taken together, these findings indicated that RMT1-10 could increase the number of TIM1+ Bregs and regulate IL-10-mediated inflammatory reactions, activate Tregs to inhibit inflammation, and might regulate the above-mentioned signaling pathways to protect against myocardial IRI.

PMID:41057354 | DOI:10.1038/s41420-025-02725-0

Phytomedicine. 2025 Sep 25;148:157302. doi: 10.1016/j.phymed.2025.157302. Online ahead of print.

ABSTRACT

BACKGROUND: Xin-Ji-Er-Kang (XJEK), a traditional Chinese medicine formulation, has shown protective effects in various murine models of cardiovascular disease. However, its potential mechanisms in mitigating drug-induced cardiotoxicity, particularly its role in regulating ferroptosis, remain unclear.

AIM OF THE STUDY: This study aimed to evaluate the cardioprotective effects of XJEK against doxorubicin (DOX)-induced myocardial injury and to elucidate its potential mechanisms.

MATERIALS AND METHODS: The protective effects of XJEK were assessed using in vivo and in vitro models of DOX-induced cardiotoxicity (DIC). Cardiac function, related biomarkers, mitochondrial function, and indicators of ferroptosis were evaluated. To clarify the mechanism, NRF2 expression was silenced using small interfering RNA (siRNA).

RESULTS: XJEK significantly alleviated DIC both in vivo and in vitro by restoring mitochondrial function, reducing lipid peroxidation, lowering reactive oxygen species (ROS) production, and decreasing iron accumulation and ferroptosis-related protein expression. Mechanistically, XJEK exerted these protective effects by inhibiting ferroptosis through activation of the NRF2 pathway.

CONCLUSION: XJEK effectively attenuates DOX-induced cardiotoxicity by suppressing ferroptosis via NRF2 activation. These findings suggest that NRF2-mediated anti-ferroptosis signalling contributes to the cardioprotective effects of XJEK, highlighting its therapeutic potential for managing drug-induced myocardial injury.

PMID:41056858 | DOI:10.1016/j.phymed.2025.157302

Ecotoxicol Environ Saf. 2025 Oct 6;304:119156. doi: 10.1016/j.ecoenv.2025.119156. Online ahead of print.

ABSTRACT

Among adults without a history of cardiovascular diseases (CVD), we estimated the effects of urinary bisphenol A (BPA) and plasma nitric oxide metabolites (NOx) on risks of 24-h ST-segment depression events (STDE) and T-wave inversion events (TIE), two indicators of myocardial ischemia, recorded in five types of leads (i.e., anterior, anterolateral, lateral, inferior and all leads) by 12-lead Holter monitors. Target genes for BPA exposure and myocardial ischemia were identified by network toxicology analyses. Furthermore, we explored whether L-arginine (L-Arg, a substrate for NO synthesis) supplementation (9 g/day) could mitigate the potential adverse effects of BPA exposure on STDE and TIE. Among the 105 participants included in the final analyses, urinary BPA concentrations were associated with significant increases in the numbers of 24-h STDE in anterior, anterolateral and all leads, and in the numbers of 24-h TIE in all five types of leads. The inverse associations between NOx and the numbers of 24-h STDE and TIE were weakened along with the increasing BPA concentrations. A total of 1287 potential target genes were found to be associated with the influence of BPA on myocardial ischemia. Biological processes such as "response to nitric oxide" and pathways such as "vascular smooth muscle contraction" were significantly enriched. L-Arg supplementation significantly attenuated the BPA-STDE and BPA-TIE associations in most types of leads. This cross-sectional analysis, conducted in adults without a history of CVD, revealed that exposure to BPA is associated with increases in indicators of myocardial ischemia. Moreover, the adverse cardiac effects of BPA can be effectively mitigated by supplementation with L-Arg.

PMID:41056681 | DOI:10.1016/j.ecoenv.2025.119156

PLoS One. 2025 Oct 7;20(10):e0333264. doi: 10.1371/journal.pone.0333264. eCollection 2025.

ABSTRACT

Acute Myocardial Infarction (AMI) is characterized by the presence of injury caused by an ischemic event, which leads to various complications, including Heart Failure (HF), the most severe functional stage of the heart, reducing both quality of life and life expectancy. Among the factors involved in this process, essential trace elements such as zinc and selenium stand out, as they are related to cardiovascular health and may help mitigate the harmful changes resulting from AMI. The objective of this protocol is to detail the development of two systematic reviews to gather scientific evidence on the relationship between zinc and selenium and the prognosis following AMI. This protocol was developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guideline and registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the code CRD42024574424. Search strategies will be conducted using a combination of controlled and uncontrolled terms combined with Boolean operators, and the following databases will be used: MEDLINE/PubMed, EMBASE, LILACS, Scopus, Web of Science, Trip database, and World Wide Science. Cohort studies that evaluated zinc and selenium in the prognosis after AMI will be included. Two trained researchers will independently select articles, extract data, and assess the risk of bias and the quality of the evidence. A narrative synthesis will be performed, and the main findings will be presented in tables. If possible, a meta-analysis will also be conducted.

PMID:41056280 | DOI:10.1371/journal.pone.0333264

Acta Anaesthesiol Scand. 2025 Nov;69(10):e70118. doi: 10.1111/aas.70118.

ABSTRACT

BACKGROUND: Perioperative hyperoxia may be associated with increased long-term mortality, whereas perioperative antioxidants may be associated with reduced long-term mortality. This study aimed to determine if high perioperative inspiratory oxygen fraction (FiO2) (0.80) compared with normal FiO2 (0.30) would increase mortality, hospital admissions, and myocardial infarction (MI) within 1 year after surgery, and whether antioxidants compared with placebo would reduce this.

METHODS: This was the preplanned 1-year follow-up of 600 patients with cardiovascular risk factors, scheduled for noncardiac surgery. They were randomized in a 2 × 2 factorial design to perioperative FiO2 of 0.80 or 0.30 and to receive antioxidants (vitamin C and N-acetylcysteine) or matching placebo. The primary 1-year outcome was all-cause mortality, and secondary 1-year outcomes were one or more hospital admissions and MIs, respectively. All outcomes were assessed using medical records and analyzed with the Cox proportional hazards model.

RESULTS: Follow-up was completed for 594 patients (99%). Twenty-five of 298 patients (8.4%) allocated to FiO2 of 0.80 died within 1 year as compared with 17 out of 296 (5.7%) allocated to FiO2 of 0.30, HR 1.46 (95% CI, 0.79-2.70), p = 0.23. A total of 260 patients had one or more hospital admissions (44%), and seven patients had MI (1.2%) with no significant difference when comparing FiO2 of 0.80 with 0.30. Antioxidants had a HR of 0.98 (95% CI, 0.54-1.80), p = 0.96 for all-cause mortality vs. placebo. The interaction between the FiO2 and antioxidant administration was statistically significant (p = 0.04) with fatalities overrepresented in patients given 80% oxygen and placebo.

CONCLUSIONS: Differences in all-cause mortality, hospital admission, or MI were not statistically significant at 1-year follow-up for either oxygen fractions or antioxidant administration in patients undergoing major noncardiac surgery.

EDITORIAL COMMENT: In this preplanned long-term study of the VIXIE trial, no differences in total mortality, hospitalization, or myocardial infarction were found for oxygen fractions of 0.80 compared to 0.30 or antioxidant administration compared to placebo. Interestingly, the study showed a higher rate of fatalities with 80% oxygen which appeared only to be present in patients not given the antioxidant intervention, but this is hypothesis-generating and needs to be further investigated in new clinical trials.

TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03494387.

PMID:41055553 | PMC:PMC12503005 | DOI:10.1111/aas.70118

Magn Reson Med. 2025 Oct 7. doi: 10.1002/mrm.70130. Online ahead of print.

ABSTRACT

PURPOSE: The IEC 60601-2-33 standard provides consensus-based safety provisions for MRI equipment. Protection of patients against cardiac stimulation (CS) is based on limiting the maximum E-field induced by MRI gradient coils. In practice, this is achieved by imposing a conservative dB/dt threshold on any gradient waveform. The dB/dt-over-E-field conversion ratio currently used in IEC 60601-2-33 was derived in a homogeneous ellipsoid exposed to a uniform B-field and is 10 (T/s)*(V/m)-1. This limit is becoming increasingly restrictive in high performance clinical systems. We therefore evaluate dB/dt-over-E-field ratios in realistic body models and coils using state-of-the-art electromagnetic simulations.

METHODS: We performed two independent simulation studies in a total of 75 realistic body models and 13 commercial gradient systems and derived dB/dt-over-E-field ratios in the heart. We thresholded the E-field maps to mitigate the impact of staircasing artifacts in boundary voxels between the myocardium and the lungs.

RESULTS: Thresholding the E-field maps at the 99th percentile E-field value (E99) eliminates staircasing artifacts in both simulation studies. Study #1 predicts a larger range of dB/dt-over-E99 ratios (13-53 (T/s)*(V/m)-1) than study #2 (12-35 (T/s)*(V/m)-1). Despite differences in EM solvers, body models, coils, mesh resolution, and post-processing, both studies find similar worst-case ratios of dB/dt-over-E99 of 12-13 (T/s)*(V/m)-1.

CONCLUSION: Our simulations of dB/dt-over-E-field ratios for cardiac safety in MRI cover a large range of realistic clinical scenarios. An increase of the allowable dB/dt beyond the current CS limit in IEC 60601-2-33 may be feasible.

PMID:41055234 | DOI:10.1002/mrm.70130

Cardiovasc Diabetol. 2025 Oct 6;24(1):385. doi: 10.1186/s12933-025-02915-1.

ABSTRACT

BACKGROUND: Cardiovascular outcome trials have shown that glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce cardiovascular event rates more effectively than placebo and in patients with type 2 diabetes at increased cardiovascular risk. However, the generalizability of these findings to real-world settings remains uncertain.

AIM: This study aimed to evaluate the real-world cardiovascular effectiveness of sustained GLP1-RA use compared to dipeptidyl peptidase 4 inhibitor (DPP-4i) over 3.5 years.

METHODS: Using Danish nationwide registries, we emulated a target trial to assess the real-world effectiveness of GLP1-RAs in a population of individuals with type 2 diabetes mirroring the inclusion and exclusion criteria from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial. The study period was 2012-2022. Outcomes included the composite of myocardial infarction, stroke, and cardiovascular mortality (3P-MACE), as well as each component individually, alongside all-cause mortality, heart failure, angina pectoris, and revascularization. Longitudinal Targeted Minimum Loss-based Estimation, a method that adjusts for both baseline and time-varying confounding, was used to estimate absolute risks of cardiovascular outcomes under sustained use of GLP1-RA and DPP 4i (active comparator), adjusting for baseline and time-varying confounding.

RESULTS: We included 6,681 people initiating GLP1-RA and 19,072 initiating DPP-4i. Accounting for baseline and time-varying confounding, sustained GLP1-RA use showed a 2.5% (95% CI 0.8-4.1%) risk reduction of 3P-MACEover 3.5 years. Risk reductions for cardiovascular mortality, all-cause mortality, heart failure, and unstable angina pectoris were 2.3% (95% CI 1.4-3.1%), 2.5% (95% CI 0.7-4.3%), 0.9% (95% CI 0.01-1.8%), and 0.7% (95% CI 0.01-1.3%), respectively. No significant differences were observed for myocardial infarction, stroke, or revascularization with risk differences of 0.1% (95% CI -1.0 to 0.8%), 0.8% (95% CI -0.2 to 1.7%), and 0.2% (95% CI -0.7-1.1%), respectively.

CONCLUSIONS: This real-world study confirms the cardiovascular benefits of GLP1-RAs over DPP-4is, particularly for reducing cardiovascular and all-cause mortality under continuous treatment exposure in patients with type 2 diabetes at increased cardiovascular risk.

PMID:41053738 | PMC:PMC12502128 | DOI:10.1186/s12933-025-02915-1

Int J Biol Macromol. 2025 Oct 4:148069. doi: 10.1016/j.ijbiomac.2025.148069. Online ahead of print.

ABSTRACT

Global warming increases the risk of heart failure and sudden death in humans and animals due to heat stress (HS). HSP90 is important in maintaining protein structure and regulating ER homeostasis during HS. However, the exact mechanism of HS-induced myocardial injury and the specific regulatory role of HSP90 remain largely unclear. Therefore, we established the HS model using broilers and chicken primary myocardial cells (CPMCs) sensitive to HS and intervened with the ERS activator (tunicamycin, TM) or inhibitor (4-Phenylbutyric acid, 4-PBA), and the autophagy activator (Rapamycin) or antagonist (3-MA). The results showed that HS caused abnormal cardiac morphology and structure in broilers. Mechanistically, ERS, autophagy, and apoptosis were significantly promoted by HS in both the myocardial tissue and cardiomyocytes. However, intervention with TM or 4-PBA significantly exacerbated or reversed these changes, while Rapamycin or 3-MA alleviated or promoted apoptosis. Moreover, HSP90 directly regulates ERS by interacting with IRE1α or PERK. HSP90 knockdown enhances ERS-mediated autophagy and apoptosis, while HSP90 overexpression reverses these effects. In conclusion, the present research suggested that HS triggers ERS-mediated protective autophagy in broiler cardiomyocytes, which is beneficial for inhibiting apoptosis. Activating HSP90 may be a promising strategy to ameliorate HS-induced cardiac injury.

PMID:41052563 | DOI:10.1016/j.ijbiomac.2025.148069

J Pharmacol Exp Ther. 2025 Sep 10;392(10):103703. doi: 10.1016/j.jpet.2025.103703. Online ahead of print.

ABSTRACT

Sepsis is a life-threatening organ dysfunction syndrome triggered by infection and uncontrolled inflammatory responses, with sepsis-associated myocardial dysfunction being a leading cause of mortality and morbidity. Metformin, a widely prescribed antihyperglycemic drug, has shown emerging protective effects beyond glucose control. In this study, we investigated the protective role of metformin against LPS-induced injury and inflammation in H9C2 and AC16 cardiomyocytes and explored the underlying mechanisms. LPS stimulation significantly reduced cell viability, promoted apoptosis, and upregulated proinflammatory cytokines (TNFα, IL-6, and IL-1β) in H9C2 and AC16 cells. Metformin treatment markedly alleviated these effects, indicating its protective role against LPS-induced cytotoxicity and inflammation. Mechanistically, metformin significantly upregulated microRNA miR-497-5p, which directly suppressed β-transducin repeat containing E3 ubiquitin-protein ligase (BTRC) expression, leading to inhibition of IκBα degradation and NF-κB pathway activation. Importantly, miR-497-5p knockdown or BTRC overexpression partially reversed the protective effects of metformin, restoring NF-κB signaling and inflammatory cytokine production. These findings collectively demonstrate that metformin protects H9C2 and AC16 cardiomyocytes from LPS-induced injury through miR-497-5p/BTRC axis-mediated suppression of NF-κB activation and highlight the functional importance of miR-497-5p and BTRC in this regulatory process. SIGNIFICANCE STATEMENT: This study highlights the protective effects of metformin against LPS-induced H9C2 and AC16 cell injury and inflammation, revealing a novel mechanism involving miR-497-5p/BTRC axis-mediated NF-κB pathway inhibition. These findings offer insights into potential therapeutic strategies for sepsis-associated myocardial dysfunction.

PMID:41052485 | DOI:10.1016/j.jpet.2025.103703

Acta Clin Croat. 2024 Dec;63(3-4):611-618. doi: 10.20471/acc.2024.63.03-04.20.

ABSTRACT

The aim of the study was to determine major adverse cardiac events (MACE) related to the percutaneous coronary intervention (PCI) on saphenous vein graft (SVG) with a second-generation drug eluting stents in patients with previous coronary artery bypass graft (CABG). The research was conducted as a unicenter retrospective observational study which analyzed consecutive patients of both genders who had PCI on SVG from January 1, 2016 until June 30, 2019. The aim was to investigate the occurrence of MACE defined as development of periprocedural myocardial infarction, acute heart failure in the first 24 hours after PCI, unstable angina after PCI, periprocedural stroke, contrast induced nephropathy, death, acute/subacute/late stent thrombosis, and target lesion revascularization. The study included 97 consecutive patients. MACE was recorded in 20.6% of patients, more often in patients with thrombolysis in myocardial infarction grade flow ≤2. High thrombus burden (HTB) was detected in 44.3% of patients and it significantly contributed to the development of MACE. In conclusion, PCI on SVG is a highly challenging procedure, especially in patients with an acute coronary syndrome. In patients who have HTB recorded in SVG, the usage of thrombus aspiration and distal protection device can reduce the frequency of no-reflow phenomenon and consequential MACE.

PMID:41050241 | PMC:PMC12490448 | DOI:10.20471/acc.2024.63.03-04.20

Ann Med. 2025 Dec;57(1):2568722. doi: 10.1080/07853890.2025.2568722. Epub 2025 Oct 6.

ABSTRACT

BACKGROUND: Cardiomyopathy is a significant cause of mortality in dystrophinopathy, and early detection and intervention are critical to reduce the disease burden. Currently, cardiomyopathy detection primarily relies on echocardiography and cardiac magnetic resonance imaging (CMR), which are inconvenient for paediatric patients and those in remote areas. Uric acid (UA) is associated with various heart diseases and serves as a biomarker of injury severity, but its level changes and connection with myocardial injury in dystrophic cardiomyopathy remain unclear. Therefore, we investigated the relationship between UA and cardiomyopathy in dystrophinopathy, as its early detection may offer a more straightforward method for monitoring cardiac health.

METHOD: A total of 71 dystrophinopathy patients underwent biochemical, genetic, and echocardiography assessments to correlate UA, gene mutations types, and cardiac parameters.

RESULT: Patients with hyperuricaemia showed larger atria and ventricles, and thicker left ventricular walls compared to those with normal UA levels. This was reflected in increased left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left atrial diameter (LAD), right ventricular diameter (RVD), left ventricular posterior wall thickness (LVPWT), and interventricular septal thickness (IVST). Multivariate linear regression analysis revealed an independent positive correlation between UA and these echocardiographic parameters.

CONCLUSION: Elevated serum UA levels were independently associated with cardiac morphological changes, including cardiac dilation and left ventricular remodelling in dystrophinopathy patients. Consequently, UA may be considered as a potential biomarker for cardiomyopathy in dystrophinopathy.

PMID:41047935 | PMC:PMC12502115 | DOI:10.1080/07853890.2025.2568722

Apoptosis. 2025 Oct 5. doi: 10.1007/s10495-025-02192-z. Online ahead of print.

ABSTRACT

Myocardial ischemia-reperfusion (I/R) injury remains a major challenge in cardiovascular interventions. Although conventional reperfusion therapies restore coronary blood flow, they can often exacerbate myocardial damage. In recent years, ferroptosis, a novel form of regulated cell death characterized by iron-dependent lipid peroxidation, has emerged as a pivotal contributor to myocardial I/R injury. Unlike apoptosis and necrosis, ferroptosis is driven by the accumulation of reactive iron and the peroxidation of membrane phospholipids enriched with polyunsaturated fatty acids (PUFAs), processes that are tightly regulated by lipid metabolism. However, the precise mechanisms linking lipid metabolic reprogramming to ferroptosis during myocardial I/R injury remain incompletely understood. To address this gap, this review systematically examines the interplay between lipid metabolism and ferroptosis in myocardial I/R injury. We highlight the roles of fatty acid uptake, β-oxidation, phospholipid remodeling, cholesterol metabolism, and mitochondria-lipid droplet interactions in forming a deleterious cycle of metabolic disruption, oxidative stress, and membrane damage. Key regulators, such as acyl-CoA synthetase long-chain family member 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and cluster of differentiation 36 (CD36), are emphasized for their roles in contributing to ferroptotic vulnerability. Moreover, the review also explores the protective roles of short-chain fatty acids (SCFAs) and 7-dehydrocholesterol (7-DHC) as emerging anti-ferroptotic agents. Novel yet understudied mechanisms with therapeutic potential are also discussed, including Rab8a-PLIN5-mediated lipid droplet trafficking and 7-DHC reductase (DHCR7) deficiency-induced 7-DHC accumulation. Collectively, this review provides a comprehensive framework for understanding the lipid metabolism-ferroptosis axis in myocardial I/R injury, offering insights for future mechanistic studies and clinical translation.

PMID:41047443 | DOI:10.1007/s10495-025-02192-z

Am J Cardiol. 2025 Oct 3:S0002-9149(25)00556-9. doi: 10.1016/j.amjcard.2025.09.008. Online ahead of print.

ABSTRACT

Surgical revascularization is still considered the gold standard for patients with complex coronary artery disease and left ventricular dysfunction. The advent of Impella has sparked growing interest, yet current evidence on its efficacy remains inconclusive. All studies reporting outcomes beyond 30 days outcomes of pPCI with any Impella device were included. Pooled effect of estimated outcomes was calculated according to a random-effect model with generic inverse variance weighting. Primary endpoint was all-cause mortality. Secondary outcomes were myocardial infarction, repeat revascularization, rehospitalization for heart failure and stroke. Six studies globally encompassing 1,581 patients were included in the quantitative analysis. Median age was 70 years old (IQR 69 to 72) with a median left ventricular ejection fraction (LVEF) of 27 % (SD ± 6) and a SYNTAX SCORE of 31 (IQR 29 to 35). Impella 2.5 was the most common micro axial flow pump used to support high-risk PCI. All-cause of death was observed in 13.4% (95% CI: 10.4 to 16.4) of patients at 6 months median follow-up. Myocardial infarction occurred in 5.8% (95% CI 3.4 to 8.1) of patients, repeat revascularization in 9.1% (95% CI: 4.8 to 13.3) of patients, stroke in 1.6% (IQR 1.2 to 2.1) of patients and, finally, heart failure rehospitalization in 8.4% (95% CI 3.3 to 13.6) of patients. In conclusion, for high-risk patients, PCI with the Impella device represented a viable strategy with an acceptable risk profile when surgical revascularization is not an option, and a poor prognosis is predicted.

PMID:41046995 | DOI:10.1016/j.amjcard.2025.09.008

Tissue Cell. 2025 Sep 29;98:103163. doi: 10.1016/j.tice.2025.103163. Online ahead of print.

ABSTRACT

BACKGROUND: (STL) is an extensively used anti-depressant drug that has been reported to induce organ damage including cardiac impairments. Nepetin (NEP) is a naturally derived flavonoid which exhibits excellent biological as well as pharmacological properties.

METHODOLOGY: This research investigation explored the cardioprotective ability of NEP to counter STL induced cardiotoxicity in Sprague Dawley rats. Thirty-six male Sprague Dawley rats were categorized into control, STL (20 mg/kg), STL (20 mg/kg) + NEP (10 mg/kg), and NEP (10 mg/kg) alone treated group.

RESULTS: NEP intoxication significantly suppressed the expression of Notch 1, JAG1, DDL4, HES1, and HEY2 while escalating the levels of ROS and MDA. Besides, STL administration increased intraventricular septal thickness during IVSd and IVSs, promoted the internal diameter of left ventricular as well as elevated ESV as while reducing PWs and PWd, LVEF, and LVFS in echocardiographic examination. The enzymatic activities of HO-1, SOD, GPx, GSR, GST, CAT, and contents of GSH were reduced while the levels of CPK, ProBNP, troponin-T, CK-MB, LDH, C-reactive protein, BNP, and troponin-I were promoted after STL intoxication. Moreover, the levels of COX-2, IL-6, TNF-α, NF- κB, and IL-1β were elevated after STL exposure. Histopathological analysis showed abnormal cardiac architecture following the administration of STL. Importantly, NEP therapy significantly conferred cardio-protection via regulating redox state, reactivating Notch signaling, suppressing inflammatory responses, and improving histopathological alterations. Moreover, echocardiographic parameters were also found normal after NEP supplementation. These findings highlight the cardioprotective role of NEP in mitigating anti-depressant drugs induced cardiotoxicity.

CONCLUSION: NEP confers cardio-protection against STL-induced cardiotoxicity via regulating oxidative stress, notch signaling, inflammation and cardiac function markers. These findings suggest this compound a promising therapy to mitigate anti-depressant drug-induced cardiac damage.

PMID:41046804 | DOI:10.1016/j.tice.2025.103163

Histochem Cell Biol. 2025 Oct 4;163(1):94. doi: 10.1007/s00418-025-02426-w.

ABSTRACT

Coenzyme Q10 (CoQ10) is an antioxidant known for its potential protective effects against various types of cardiac injury. The aim of this study was to determine the protective effects of CoQ10 on cardiomyocytes, telocytes and progenitor cells in rats with isoproterenol (ISO)-induced cardiotoxicity. A total of 60 Sprague-Dawley rats were divided into six groups (n = 10): Group I: control, Group II: saline control, Group III: oil control, Group IV: ISO, Group V: CoQ10, Group VI: ISO and CoQ10. Isoproterenol was administered intraperitoneally at a dose of 85 mg/kg twice on the eighth and ninth days, and CoQ10 was administered by oral gavage at a daily dose of 20 mg/kg. Heart tissue samples were collected and analysed at the end of the study. CoQ10 reduced ISO-induced cardiac degeneration, necrosis, inflammatory infiltration and fibrosis. The stimulation of cell cycle activators such as histone H3 and proliferating cell nuclear antigen (PCNA) was found to play a role in the repair of cardiac injury in the cardiomyocytes known to be postmitotic. An increase in c-Kit and CD34 stem cells was seen with the beneficial effect of CoQ10 (P < 0.05). The presence of telocytes, which play an important role in cardiac regeneration, was visualised by double CD34-c-Kit and CD34-vimentin immunofluorescence staining. The results indicate that CoQ10, through its antioxidant effect, ameliorates cardiac lesions caused by ISO, induces a limited number of cell cycle activators in cardiomyocytes and interstitial cells and has a positive effect on the increase of progenitor cells in the heart.

PMID:41046280 | DOI:10.1007/s00418-025-02426-w

Clin Transl Med. 2025 Oct;15(10):e70494. doi: 10.1002/ctm2.70494.

ABSTRACT

OBJECTIVES: Although extensive research on septic cardiomyopathy has been conducted, effective therapies are still limited. Ubiquitin-specific peptidase 20 (USP20), a deubiquitinating enzyme, is critical in regulating protein ubiquitination and various cellular processes. whether USP20 is involved in the pathogenesis of septic cardiomyopathy remains unclear. This study investigated the impact of USP20 on septic cardiomyopathy.

METHODS: The cardiomyocyte-specific USP20 knockout mice (USP20CKO) and NLRP3 knockout mice (NLRP3-/-) were used in the present study. A sepsis mouse model was established using lipopolysaccharide (LPS) administration and the cecal ligation and puncture (CLP) procedure. Recombinant adeno-associated virus serotype 9 (AAV9) was used to achieve overexpression of USP20. Myocardial function, histopathological changes, and pyroptosis levels in heart tissues were evaluated. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis and co-immunoprecipitation (co-IP) were performed to identify the molecular mechanism of USP20 in septic cardiomyopathy.

RESULTS: Our results showed that USP20 was downregulated in the myocardium of septic mice. Cardiomyocyte-specific USP20 deficiency worsened myocardial injury and cardiac dysfunction induced by LPS and CLP. LC-MS/MS analysis and co-IP revealed NLRP3 as a substrate protein of USP20. Mechanistically, USP20 removed K63-linked ubiquitin from K243 via its active site C154, inhibiting NLRP3's interaction with ASC and suppressing its activation and subsequent pyroptosis. Moreover, overexpressing USP20 in cardiomyocytes reduced LPS-induced myocardial injury. Additionally, the protective effect of USP20 against LPS-induced damage was nullified in the absence of NLRP3 in mice.

CONCLUSIONS: These findings suggest that cardiomyocyte-derived USP20 is crucial in septic cardiomyopathy progression and may serve as a novel therapeutic target for managing septic cardiomyopathy.

KEY POINTS: Cardiomyocyte-derived USP20 is crucial in septic cardiomyopathy progression. NLRP3 is identified as a substrate protein of USP20. USP20 deubiquitinates NLRP3 by removing K63-linked ubiquitin at K243 residue via its active site C154, disrupting the interaction between NLRP3 and ASC, suppressing NLRP3 activation and subsequent pyroptosis. USP20 may serve as a novel therapeutic target for managing septic cardiomyopathy.

PMID:41042219 | PMC:PMC12493026 | DOI:10.1002/ctm2.70494