Protección miocárdica

In Vivo. 2025 Jul-Aug;39(4):2066-2072. doi: 10.21873/invivo.14001.

ABSTRACT

BACKGROUND/AIM: The aim of the present study was to investigate on the repurposing of glatiramer acetate (GA), a drug traditionally used to treat multiple sclerosis, as well as explore GA potential to treat cardiac ischemia in rodent models. It has been shown that GA exerts immunomodulatory effects that reduced inflammation and increased repair of heart tissue following myocardial infarction (MI) in mice and rats. GA has been shown to enhance cardiac function by promoting angiogenesis, reducing scar tissue, and protecting cardiomyocytes from ischemic damage.

MATERIALS AND METHODS: Risteys/FinnGen and MedWatch/OpenVigil data were used to assess the effects of GA on the heart.

RESULTS: There was significantly less ischemic heart disease (p<0.001, Fisher's exact test) and cardiovascular disease (p<0.001) in 457 subjects with MS who used GA in Risteys/FinnGen. Analysis of MedWatch/OpenVigil data showed a significantly reduced risk of acute MI in individuals using GA, with a proportional reporting ratio (PRR) of 0.101, indicating statistical significance at the 95% confidence level. Additionally, analysis of MedWatch/OpenVigil data indicated a decreased risk of cardiovascular disease in GA users, with a PRR of 0.345, reaching statistical significance at the 95% confidence level.

CONCLUSION: Despite rare adverse cardiovascular side-effects and given its established safety profile, GA shows promise as a novel treatment option for heart disease. Further studies could lead to an important new use of GA especially in patients who do not receive tissue plasminogen activator within the first few hours following an MI.

PMID:40579010 | DOI:10.21873/invivo.14001

Anticancer Res. 2025 Jul;45(7):2905-2916. doi: 10.21873/anticanres.17658.

ABSTRACT

BACKGROUND/AIM: Doxorubicin (DOX) is the most impactful drug developed for osteosarcoma. However, despite its therapeutic effects, it also causes serious side effects, such as cardiotoxicity and hemotoxicity. To address this, we developed a novel DOX prodrug that exhibits high antitumor activity specifically in hypoxic regions while demonstrating low toxicity in normal organs. Based on these properties, we evaluated its efficacy against osteosarcoma with the aim of significantly reducing side effects while maintaining therapeutic efficacy.

MATERIALS AND METHODS: To evaluate antitumor effects, tumor diameter changes were measured in osteosarcoma cell line-bearing mice divided into the following groups: control, DOX 8 mg/kg, DOX prodrug 8 mg/kg, and 5 doses of DOX prodrug 16 mg/kg every other day. To evaluate side effects, blood samples were collected 2 weeks after treatment in all groups to determine the complete blood count and aspartate aminotransferase, alanine aminotransferase, creatinine, and blood urea nitrogen levels. After the mice were sacrificed, sections of the liver, kidney, heart, and testes were prepared for histological evaluation.

RESULTS: Regarding antitumor effects, the DOX and DOX prodrug groups showed comparable reductions in tumor size when compared to the control group. Blood test results showed that mice in the DOX prodrug group had no leukopenia or liver dysfunction. Histological evaluation revealed that the DOX prodrug group showed significantly less myocardial damage and gonadal toxicity compared to the DOX group.

CONCLUSION: The DOX prodrug developed by our group showed tumor-suppressive effects comparable to those of DOX while being able to suppress blood toxicity, cardiotoxicity, as well as liver and testicular dysfunction.

PMID:40578960 | DOI:10.21873/anticanres.17658

Eur J Med Chem. 2025 Jun 10;296:117802. doi: 10.1016/j.ejmech.2025.117802. Online ahead of print.

ABSTRACT

Heart failure (HF) is a progressive disease characterized by persistent or episodic worsening of symptoms, leading to functional deterioration. Clinically, guidelines recommend the use of SGLT2 inhibitors for the treatment of heart failure. However, the SGLT2 inhibitors exist potential risks including weight loss and euglycemic diabetic ketoacidosis. We designed and synthesized a series of O-glucoside derivatives by introducing nitrogen-containing heterocyclic fragments. Among them, compound E9 showed the most protective effect on the glucose-free DMEM-induced injured cardiomyocytes, and the structure-activity relationships (SAR) of these compounds were preliminarily evaluated in cardiomyocyte injury model. Furthermore, compound E9 significantly enhanced the inhibition of SGLT2, NHE1, and SOD enzyme activity, increased ATP levels in damaged cardiomyocytes, and suppressed Ang II-induced myocardial fibrosis, the autophagy receptor protein P62 and the expression of cell injury markers. Additionally, compound E9 significantly improved cardiac function in TAC-induced HF mice, inhibited cardiomyocyte hypertrophy and collagen deposition, ameliorated myocardial tissue damage, enhanced mitochondrial autophagy in injured cardiomyocytes, and ultimately increased survival rates in HF mice. In conclusion, this study reveals that the novel O-glucoside derivative E9 was a promising compound for the treatment of heart failure.

PMID:40578252 | DOI:10.1016/j.ejmech.2025.117802

Environ Int. 2025 Jun 24;202:109617. doi: 10.1016/j.envint.2025.109617. Online ahead of print.

ABSTRACT

BACKGROUND: Air pollution has been linked to cardiovascular diseases (CVDs). In this study, we assess whether exposure to air pollutants and ambient temperature is associated with repeated admissions with adverse cardiovascular outcomes.

METHODS: We used data from Medicare beneficiaries between 2000 and 2016 to look at the effects of intermediate and long-term exposure to ambient PM2.5, NO2, O3, and temperature on second admissions with myocardial infarction (MI) and ischemic stroke. We derived exposure levels from high-resolution spatiotemporal models. We adjusted for demographic, socioeconomic, and access-to-care characteristics. Cox proportional hazards models were used to assess these relationships. We further looked at the effects of exposure at lower air pollution concentrations defined as PM2.5 < 9 µg/m3, NO2 < 25 ppb, and O3 < 50 ppb.

RESULTS: PM2.5 and NO2 increased the hazard of second admissions with both MI and stroke. For PM2.5, the effects were more pronounced for longer exposure time windows. Each µg/m3 increase in one-year PM2.5 levels before the first admission increased the hazard of a second admission with MI by 1.1% (95% CI: 1.0%-1.2%) and stroke by 0.9% (95% CI: 0.8%-1.1%). O3 exhibited a slight protective effect for both outcomes. Higher temperatures were associated with a higher hazard of second admissions with stroke. These results persisted at lower concentrations.

CONCLUSION: Our study demonstrates that exposures to PM2.5 and NO2 are associated with increased rates of second admissions with MIs and strokes. Higher temperatures were also further associated with an increase in the rate of second admissions with stroke.

PMID:40578117 | DOI:10.1016/j.envint.2025.109617

J Mol Histol. 2025 Jun 27;56(4):207. doi: 10.1007/s10735-025-10453-z.

ABSTRACT

Myocardial ischemia followed by reperfusion triggers a range of pathological events, among which excessive autophagy plays a key role. Theaflavin-3,3'-digallate (TF3) is a functional polyphenol of black tea and is beneficial in the prevention or/and treatment of various diseases. Here, we explored the therapeutic effect of TF3 on myocardial ischemia/reperfusion (I/R) injury. I/R injury was induced in rats through ischemia (30 min) followed by reperfusion (24 h). TF3 was administered seven days before the I/R. Cardiac function was determined by echocardiography. Infarct size and apoptosis were assessed using TTC and TUNEL, respectively. H9C2 cardiomyocytes were treated with TF3 or/and PI3K inhibitor (LY294002) and then exposed to hypoxia/reoxygenation (H/R). Content levels of myocardial injury indicators in rat hearts and H9C2 cardiomyocytes were detected using corresponding kits. H9C2 cardiomyocyte apoptosis was evaluated by flow cytometry. Protein levels of autophagy, apoptosis, and PI3K/Akt/mTOR signaling in vivo and in vitro were detected using western blotting. TF3 reduced myocardial infarct size and decreased serum CK-MB, cTnT, and LDH content levels in rat model of myocardial I/R. TF3 reduced apoptosis and autophagy in I/R rat hearts and H9C2 cardiomyocytes by reducing Bax, cleaved caspase-3, Beclin-1, and LC3B levels, and elevating Bcl-2 and p62 levels. TF3 administration activated PI3K/Akt/mTOR signaling in I/R rat hearts and H9C2 cells. PI3K inhibitor LY294002 reversed the inhibitory effect of TF3 on H/R-induced apoptosis and autophagy in H9C2 cells. Overall, TF3 alleviates I/R-induced myocardial injury by reducing autophagy and apoptosis by activating PI3K/Akt/mTOR signaling.

PMID:40576913 | DOI:10.1007/s10735-025-10453-z

Ann Nucl Med. 2025 Jun 27. doi: 10.1007/s12149-025-02077-w. Online ahead of print.

ABSTRACT

PURPOSE: The study aimed to assess the prognostic value of non-perfusion parameters for gated myocardial perfusion imaging (MPI) performed using Cadmium-Zinc-Telluride (CZT) single-photon emission computed tomography (SPECT) for individuals with normal myocardial perfusion.

METHODS: We analyzed data from consecutive patients who underwent thallium-201 MPI SPECT with normal perfusion. Major adverse cardiovascular events (MACEs) were recorded during a 2-year follow-up. Non-perfusion parameters were evaluated as predictors of MACEs.

RESULTS: Among 1570 patients with normal SPECT perfusion, 80 (5.1%) experienced MACEs over a mean follow-up of 22.5 ± 10.8 months: 12 (0.8%) had cardiac death, and 68 (4.3%) underwent coronary revascularization due to significant coronary artery disease. Independent predictors of MACEs included worsening post-stress ejection fraction (HR: 1.971; p = 0.008), and increased lung-to-heart ratio (HR: 2.207; p = 0.001). Kaplan-Meier analysis showed the highest MACEs' incidence in patients with two of these factors (p < 0.001). Among patients with normal resting ejection fraction, EF worsening (OR: 2.16; p = 0.004) and increased lung-to-heart ratio (OR: 1.91; p = 0.0013) both remained strong predictors.

CONCLUSIONS: Although normal myocardial perfusion typically indicates low risk for obstructive coronary artery disease, worsening post-stress ejection fraction and increased lung-to-heart ratio are crucial prognostic indicators. Importantly, these non-perfusion parameters retain their prognostic value even in patients without clinical heart failure, highlighting their relevance in comprehensive risk stratification beyond perfusion assessment alone.

PMID:40576735 | DOI:10.1007/s12149-025-02077-w

Mol Med Rep. 2025 Sep;32(3):237. doi: 10.3892/mmr.2025.13602. Epub 2025 Jun 27.

ABSTRACT

The specific mechanisms of doxorubicin (Dox)‑induced cardiotoxicity (DIC) remain unclear. In the present study, H9c2 cardiomyocytes were treated with Dox, and it was revealed that DEAD‑box RNA helicase 3 X‑linked (DDX3X), mitochondrial antiviral signaling (MAVS) and stress granules (SGs) were present at lower levels in the treated H9c2 cardiomyocytes compared with those in the control cells. The present study further investigated the mechanisms through which DIC occurs. Pretreatment with arsenite, which pharmacologically accelerates SGs, alleviated the myocardial injury caused by Dox. By contrast, anisomycin, an SG inhibitor, increased cardiomyocyte apoptosis induced by Dox. In addition, both DDX3X knockdown and pretreatment with RK‑33 (a DDX3X pharmacological inhibitor) decreased SG expression, whereas DDX3X overexpression promoted SG generation. These results indicated that DDX3X mitigated DIC through the regulation of SGs. In addition, MAVS knockdown inhibited SG assembly and reduced the expression of the anti‑apoptotic inhibitor Bcl2, and MAVS was influenced by DDX3X, thereby serving as a connector between DDX3X and SGs. The results from western blotting, reverse transcription‑quantitative PCR, immunofluorescence and flow cytometry analysis demonstrated that DDX3X, MAVS, and SGs may serve as key protective factors in DIC.

PMID:40576139 | DOI:10.3892/mmr.2025.13602

World J Cardiol. 2025 Jun 26;17(6):104832. doi: 10.4330/wjc.v17.i6.104832.

ABSTRACT

BACKGROUND: Right ventricular hypertrophy (RVH) occurs because of volume or pressure overload within the right ventricular (RV) system. RVH is associated with complex pathological changes, including myocardial cell injury, apoptosis, myocardial fibrosis, neuroendocrine disturbances, and abnormal water and liquid metabolism. Ferroptosis, a novel type of iron-dependent cell death characterized by lipid peroxide accumulation, is an important mechanism of cardiomyocyte death. However, the role of ferroptosis in RVH has rarely been studied. We hypothesize that hydrogen (H2), an experimental medical gas with superior distribution characteristics, inhibits ferroptosis.

AIM: To explore the protective effect of H2 on RVH and the mechanism by which H2 regulates ferroptosis.

METHODS: An in vivo RVH rat model was induced by monocrotaline (MCT) in 30 male Sprague-Dawley rats. An H9C2 cell model was treated with angiotensin II to simulate pressure overload in the RV system in vitro. H2 was administered to rats by inhalation (2% for 3 hours daily for 21 days) and added to the cell culture medium. The Nrf2 inhibitor ML385 (1 μM) was used to investigate anti-ferroptotic mechanisms.

RESULTS: In MCT-treated rats, H2 inhalation decreased RVH; the RV wall thickness decreased from 3.5 ± 0.3 mm to 2.8 ± 0.2 mm (P < 0.05) and the RV ejection fraction increased from 45 ± 3% to 52 ± 4% (P < 0.05). In H9C2 cells, H2 alleviated hypertrophy. H2 inhibited ferroptosis by modulating the iron content, oxidative stress, and ferroptosis-related proteins, thereby restoring the Nrf2/HO-1 signaling pathway.

CONCLUSION: H2 retards RVH by inhibiting ferroptosis via Nrf2/HO-1 restoration, suggesting a new treatment strategy.

PMID:40575431 | PMC:PMC12186143 | DOI:10.4330/wjc.v17.i6.104832

Front Physiol. 2025 Jun 12;16:1641580. doi: 10.3389/fphys.2025.1641580. eCollection 2025.

ABSTRACT

[This retracts the article DOI: 10.3389/fphys.2020.551318.].

PMID:40574900 | PMC:PMC12198966 | DOI:10.3389/fphys.2025.1641580

Medicina (Kaunas). 2025 May 30;61(6):1020. doi: 10.3390/medicina61061020.

ABSTRACT

Galectin-1 (Gal-1), a β-galactoside-binding lectin, plays a complex role in cardiovascular diseases (CVDs), exerting both protective and pathological effects depending on the context. This review synthesizes findings from the past decade to explore Gal-1's involvement in key aspects of CVD pathogenesis, including vascular homeostasis, inflammation regulation, atherosclerosis progression, myocardial remodeling, and heart failure. While Gal-1 supports endothelial integrity and immune modulation, its dysregulation contributes to disease progression through pro-inflammatory signaling, fibrosis, and adverse cardiac remodeling. Emerging evidence suggests that Gal-1 holds potential as both a biomarker for risk assessment and a therapeutic target. However, critical knowledge gaps remain, particularly regarding its context-dependent effects, the limited scope of clinical trials, and unresolved mechanistic insights. Addressing these challenges will be essential to fully harness Gal-1's therapeutic potential in cardiovascular medicine, guiding future research efforts toward precision interventions and clinical applications.

PMID:40572708 | PMC:PMC12195248 | DOI:10.3390/medicina61061020

Molecules. 2025 Jun 10;30(12):2527. doi: 10.3390/molecules30122527.

ABSTRACT

Anthracyclines play an irreplaceable role in cancer treatment, although their clinical application is limited due to severe side effects such as arrhythmia, cardiomyopathy, and myocardial infarction. The currently available clinical drugs for treating anthracycline-induced cardiotoxicity (AIC) are limited by numerous drawbacks, including the side effects of the therapeutic agents, single treatment mechanisms, and individual patient variations. Therefore, novel drugs with broader applicability and multitarget synergistic protective effects are, therefore, urgently needed. Ginsenosides, the primary bioactive constituents of plants belonging to the genus Panax (family Araliaceae), exhibit a wide range of pharmacological activities, including anti-inflammatory, antioxidative, and antitumor effects, and have demonstrated cardioprotective properties against AIC. This article examines the mechanisms of AIC and the modulatory effects of ginsenosides on these mechanisms. This review highlights the potential molecular targets and signaling pathways through which ginsenosides exert therapeutic effects on AIC, including the regulation of oxidative-stress-related pathways such as Keap1/Nrf2, MAPK, STAT, PI3K/Akt, and AMPK; the restoration of mitochondrial function; the modulation of autophagy; and the inhibition of pyroptosis, ferroptosis, and apoptosis. Therefore, this review serves as a theoretical basis and provides a research direction for future investigation regarding the prevention and treatment of AIC with ginsenosides, as well as clinical translation studies.

PMID:40572494 | PMC:PMC12196387 | DOI:10.3390/molecules30122527

Int J Cardiol. 2025 Jun 24:133542. doi: 10.1016/j.ijcard.2025.133542. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains debated, particularly for bifurcation lesions, which are associated with increased thrombotic risk. Shorter DAPT regimens may reduce bleeding but could compromise ischemic protection.

METHODS: This study analyzed data from the ULTRA and BIFURCAT registries, including patients treated with PCI for bifurcation lesions. Patients requiring oral anticoagulation were excluded. DAPT duration was categorized as ≤6 months, 6-12 months and > 12 months. The primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, target lesion revascularization, and stent thrombosis. Cox regression analysis was used to assess the association between DAPT duration and MACE.

RESULTS: Among 6729 patients, 425 (6 %) received DAPT ≤6 months, 3446 (51 %) for 6-12 months and 2858 (42 %) for >12 months. At 800-day follow-up, MACE rates were higher with shorter DAPT (19.5 % vs. 10 % vs. 5.9 %, p < 0.001). Adjusted hazard ratios for MACE were significantly higher for DAPT ≤6 months (HR 4.8, 95 % CI 1.8-12.7) and 6-12 months (HR 2.7, 95 % CI:1.5-4.7) compared to >12 months. This trend was consistent in acute coronary syndrome (ACS) patients but not in stable patients.

CONCLUSION: In PCI-treated bifurcation lesions, particularly in ACS patients, shorter DAPT duration (≤6 months) is associated with a higher risk of adverse events. These findings, albeit hypothesis generating, highlight the need to consider bifurcation lesions as a key factor in tailoring DAPT duration and may warrant confirmation in dedicated trials.

PMID:40571129 | DOI:10.1016/j.ijcard.2025.133542

PLoS One. 2025 Jun 26;20(6):e0326534. doi: 10.1371/journal.pone.0326534. eCollection 2025.

ABSTRACT

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) and diabetes mellitus (DM) are interrelated conditions associated with high morbidity and mortality. This study compared the cardiovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus sodium-glucose cotransporter-2 (SGLT2) inhibitors in this population.

METHODS: This retrospective cohort study used data from the TriNetX database. It included 2,177 matched pairs of patients with HFpEF and DM treated with either GLP-1 RAs or SGLT2 inhibitors. Outcomes assessed over three years were a composite of all-cause mortality and progression to systolic heart failure, acute myocardial infarction, or stroke.

RESULTS: GLP-1 RAs significantly reduced the risk of composite outcomes at one year (Hazard Ratio, HR 0.784; 95% CI, 0.658-0.934), two years (HR 0.813; 95% CI, 0.702-0.941), and three years (HR 0.825; 95% CI, 0.717-0.950). Specifically, GLP-1 RAs showed significantly reduced risks of progression to systolic heart failure (HR 0.60) and stroke (HR 0.75) compared to SGLT2 inhibitors. These protective effects were most pronounced in the first year and showed a slightly diminishing trend. While not statistically significant, GLP-1 RAs also exhibited a trend towards fewer myocardial infarctions (HR 0.83) and lower mortality rates (HR 0.83) than SGLT2 inhibitors. Subgroup analyses revealed more significant benefits in patients aged ≥60, women, Caucasians, those without moderate-to-severe chronic kidney disease or chronic ischemic heart disease, and those with better-controlled DM.

CONCLUSIONS: Among HFpEF patients with DM, GLP-1 RAs demonstrated superior cardiovascular protective effects compared with SGLT2 inhibitors over a 3-year follow-up period. Further randomized trials are required to confirm these findings.

PMID:40570020 | PMC:PMC12200838 | DOI:10.1371/journal.pone.0326534

J Funct Morphol Kinesiol. 2025 Jun 2;10(2):206. doi: 10.3390/jfmk10020206.

ABSTRACT

Background: Sprinting, a high-intensity, short-duration exercise, induces oxidative stress. This causes molecular and ultrastructural alterations. Antioxidant supplementation may mitigate side effects of near or complete exhaustion. Methods: Twenty-eight healthy male adult rats received orally normal saline, carboxymethylcellulose (vehicle), artificial, N-acetylcysteine or a natural antioxidant, Rutin. Rats were subjected to treadmill sprinting at increasing speeds for 5 days/week. After 26 days, samples were collected to measure oxidative stress (malondialdehyde, MDA; the ratio of reduced-to-oxidized glutathione, GSH/GSSG), inflammation markers (enzymatic level of inducible nitric oxide synthase, iNOS; cytokine level of tumor necrosis factor alpha, TNFα) and for transmission electron microscopy (TEM) analysis. Results: Rutin attenuated MDA levels and increased antioxidant protection in all tissues, while NAC decreased the lipid peroxidation in all tissues except the lungs. NAC increased aortic inflammation, with higher TNF-α and iNOS. Sprinting caused intimal detachment in the heart and aorta. Rutin and NAC minimized endocardium alterations. Additionally, Rutin prevented myocardial disorganization. Conclusions: Rutin mitigated the oxidative stress damage of sprinting in the heart, aorta, skeletal muscle and lung. NAC protected against oxidative injury caused by sprinting in the heart, aorta and muscle but not the lung, and it induced aortic inflammation.

PMID:40566456 | PMC:PMC12194789 | DOI:10.3390/jfmk10020206

Int J Mol Sci. 2025 Jun 11;26(12):5612. doi: 10.3390/ijms26125612.

ABSTRACT

Low-density lipoprotein cholesterol (LDL-C) plays a central role in lipid metabolism and is a well-established therapeutic target for the prevention of atherosclerotic cardiovascular diseases (CVDs). In recent years, increasingly aggressive lipid-lowering strategies have been adopted to achieve ultra-low LDL-C concentrations (<55 mg/dL or even <30 mg/dL) in high-risk patients. While the benefits of LDL-C reduction in lowering the incidence of myocardial infarction and ischemic stroke are well documented, emerging clinical evidence has raised concerns about a potential association between very low LDL-C levels and an increased risk of bleeding, particularly hemorrhagic stroke and gastrointestinal hemorrhage. This review critically examines the molecular mechanisms by which reduced LDL-C levels may influence the hemostatic system and vascular integrity. It explores the complex interplay between cholesterol availability and platelet function, endothelial barrier stability, and coagulation pathways. In addition, we assess experimental and clinical studies supporting this association and discuss how these findings may inform risk stratification and personalized lipid-lowering strategies. A deeper understanding of the biological basis of this paradoxical risk is essential for achieving a safe, balanced, and effective approach to cardiovascular prevention.

PMID:40565076 | PMC:PMC12192760 | DOI:10.3390/ijms26125612

Int J Mol Sci. 2025 Jun 10;26(12):5542. doi: 10.3390/ijms26125542.

ABSTRACT

Resveratrol is a natural polyphenol found in grapes, berries, and red wine, commonly studied for its biological activity. In vitro research often uses high concentrations of resveratrol applied for short incubation times. However, resveratrol reaches relatively low concentrations in vivo when it is used as a dietary supplement. Therefore, the aim of this study was to investigate the cellular response of cardiomyocytes to low, physiologically relevant concentrations of resveratrol and, in particular, to compare these responses depending on the duration of exposure. Cardiomyocytes were treated with resveratrol for either 1 day, 1 week, or 1 month. Functional assays assessing metabolic activity, cell cycle distribution, and apoptosis intensity were performed, along with analysis of selected pathways at protein levels. The results showed that the cellular response differed markedly depending on the duration of resveratrol treatment. Observed changes indicated alterations in energy metabolism and effects consistent with anti-aging activity.

PMID:40565004 | PMC:PMC12193273 | DOI:10.3390/ijms26125542

Int J Mol Sci. 2025 Jun 6;26(12):5453. doi: 10.3390/ijms26125453.

ABSTRACT

Surgical myocardial revascularization, regardless of the technique used, causes ischemia-reperfusion injury (IRI) in the myocardium mediated by inflammation and degradation of the endothelial glycocalyx (EG). We investigated the difference between on-pump and off-pump techniques in terms of the concentration of proinflammatory interleukin (IL)-18 and the EG degradation products syndecan-1 and hyaluronic acid measured by ELISA in the peripheral and cardiac circulation during open heart surgery and in the early postoperative period. The concentration of IL-18, C-reactive protein (CRP), and cardiac troponin T (cTnT) and the leukocyte count increased statistically significantly in revascularized patients at 24 and 72 h after revascularization compared to the beginning of the procedure and was always statistically significantly higher in on-pump patients. Syndecan-1 and hyaluronic acid only increased in on-pump patients 24 and 72 h after revascularization. IL-18 correlated positively with syndecan-1 and CRP only in the pump setting and with the number of leukocytes in both revascularization regimens 24 and 72 h after the surgery. cTnT and hyaluronic acid did not correlate with IL-18. Our results suggest that IL-18 plays an important role in the early inflammatory response in patients during open heart surgery and in the early postoperative period, leading to additional damage to the EG, while it is probably not responsible for myocardial necrosis. It could serve as a biomarker to identify high-risk patients and as a therapeutic target to reduce inflammation and EG degradation. In addition, measurement of IL-18 could help improve the treatment, recovery, and outcomes of patients after heart surgery.

PMID:40564918 | PMC:PMC12193331 | DOI:10.3390/ijms26125453

Biomedicines. 2025 Jun 13;13(6):1466. doi: 10.3390/biomedicines13061466.

ABSTRACT

Background: Estrogens play a protective role during the early stages of life. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression. Aim: The purpose of this study was to test for the significance of the sex-specific associations of gonadal hormones with the extent of the inflammatory response, myocardial damage, and ventricular arrhythmia risk in acute myocardial infarction (MI). Materials and Methods: Study design: single-center cohort study. Blood samples for the assessment of sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitivity C-reactive protein (CRP), white blood cell (WBC) counts, and cardiac enzymes were collected 48 h after the onset of symptoms (and within 6 h after PCI) from 111 patients (37% women) with acute MI. Coronary disease severity, left ventricular systolic function (LV), and indices of ventricular repolarization were assessed using coronary angiography, echocardiography, and a conventional electrocardiogram, respectively. Results: In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels, peak WBC count, and peak CRP plasma levels. T levels and the E2/T ratio were associated with post-PCI CRP in these men. For women, peak WBC count was a marker of highest testosterone, and only WBC count was a significant indicator of myocardial injury extent. The incidence of acute ventricular tachycardia detected in AMI was significantly associated with left ventricular ejection fraction and with peak WBC count (as a tendency) regardless of sex. A longer duration of cardiac repolarization prior to PCI was predicted by lower ejection fractions in men and by age, CRP, and testosterone levels in female patients. Conclusions: During acute MI, elevated endogenous estradiol levels in men and increased leukocytes in women indicate acute myocardial damage. Post-PCI plasma inflammatory markers are sex-specific confounding factors for acute endogenous E2 levels, T levels, and the E2/T ratio. LV systolic function in men and, characteristically, the acute inflammatory response and testosterone levels in women are predictors of longer ventricular repolarization and arrhythmia risk.

PMID:40564184 | PMC:PMC12190329 | DOI:10.3390/biomedicines13061466

Biomolecules. 2025 May 28;15(6):783. doi: 10.3390/biom15060783.

ABSTRACT

PURPOSE: Doxorubicin (DOX) is a broad-spectrum anti-tumor anthracycline drug. However, its clinical application is greatly limited due to the side effect of cardiotoxicity. Caffeic acid phenethyl ester (CAPE) is one of the major biologically active compounds isolated from propolis, which is effective in the treatment of cardiovascular diseases. The purpose of this study aimed to explore the possible mechanism of CAPE's protective effect on DOX-induced cardiotoxicity (DIC).

METHODS: In vivo, a DIC model was established by the intraperitoneal injection of 3 mg/kg DOX. The cardiac function of mice was monitored by electrocardiograms. Histopathological changes in myocardial tissue were detected by H&E staining. Serum samples were tested for the level of markers of myocardial injury. In vitro, transmission electron microscopy was used to assess the mitochondrial damage. Oxidative stress was measured by flow cytometry and mitochondrial respiration analysis. Necroptosis pathway changes were detected by Western blotting. Furthermore, the overexpression plasmid of a key necroptosis gene, necroptosis inhibitor or ROS inducer/inhibitor was applied to H9c2 and AC16 cells to explore whether CAPE exerted a protective effect against DIC through the cross-talk mediated by ROS and MLKL.

RESULTS: CAPE could improve the cardiac function and protect against myocardial tissue. CAPE pre-administration treatment attenuated the DOX-induced generation of ROS, protected mitochondrial functions and inhibited necroptosis. Moreover, there was cross-talk between the ROS and necroptosis. CAPE could protect against DIC by inhibiting the ROS-MLKL signaling that regulated the cross-talk.

CONCLUSIONS: CAPE alleviated the oxidative stress and necroptosis of DIC, indicating that the cross-talk mediated by ROS-MLKL signaling may be a potential therapeutic mechanism for clinical DIC.

PMID:40563424 | PMC:PMC12190673 | DOI:10.3390/biom15060783

Antioxidants (Basel). 2025 May 31;14(6):671. doi: 10.3390/antiox14060671.

ABSTRACT

Ginnalin A (GA), a polyphenolic compound derived from amur maple trees, has been identified as a powerful scavenger of reactive oxygen species (ROS). Recognizing the pivotal role of ROS in exacerbating secondary damage during myocardial ischemia-reperfusion injury (MIRI), we fractionated GA-enriched extracts from the leaves of the amur maple tree, Acer tataricum L. subsp. ginnala (Maxim.) Wesm., using common solvents of dichloromethane (DCM) and ethyl acetate (EA). When co-administered for 30 min, the DCM- and EA-fractioned extracts effectively protected cardiomyocytes from H2O2-induced damage. ROS-sensitive probes indicated that treatment with ginnala extracts significantly reduced both intracellular and mitochondrial ROS levels. Instead of enhancing the activity of antioxidative enzymes, the ginnala extracts acted as natural antioxidases, directly scavenging various ROS such as superoxide, H2O2, hydroxyl radical, and Fe2+ within just 20 min. In a MIRI rat model, the in vivo administration of ginnala extracts provided significant cardioprotection by preserving viable myocardia and enhancing cardiac functions. Additionally, treatment with ginnala extracts significantly reduced cardiac fibrosis and denatured collagen. Our study suggests that the ultrafast ROS scavenging capability of ginnala extracts offers substantial heart protection during MIRI. Incorporating ginnala extracts as a pharmacological intervention during reperfusion could effectively mitigate ROS-induced cardiac injury.

PMID:40563305 | PMC:PMC12189229 | DOI:10.3390/antiox14060671