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Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 26. doi: 10.1007/s00210-025-04252-2. Online ahead of print.

ABSTRACT

Nitric Oxide Synthase 3 (NOS3) G894 T (rs1799983) is an important regulator of cardiac development. Its role in congenital heart disease (CHD) has been extensively studied in recent years, but the results are contradictory. The aim of the present study was to better elucidate the relationship between the NOS3 G894 T gene polymorphism and susceptibility of CHD and its specific subtypes. A comprehensive literature search was conducted across several databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, and Wan Fang. Meta-analysis was carried out using RevMan 5.4 software, and the odds ratio (OR) with 95% confidence intervals (CI) was used as the effect measure. Additionally, bioinformatics analysis was employed to explore the impact of NOS3 gene mutations on tetralogy of Fallot (TOF), using publicly available microarray datasets to assess NOS3 gene expression. Nine studies were included, comprising 1931 CHD cases and 1910 controls. Meta-analysis showed that the NOS3 G894 T polymorphism was associated with an increased risk of CHD in three genetic models: allele model (T vs G, OR = 1.31, 95% CI [1.02, 1.68], P = 0.04), homozygous model (TT vs GG, OR = 1.60, 95% CI [1.13, 2.26], P = 0.007), and dominant model (GT + TT vs GG, OR = 1.44, 95% CI [1.02, 2.05], P = 0.04). Subgroup analyses revealed a strong association with atrial septal defect (ASD), conotruncal defects (CTD), and septal defects, with the most significant correlation found for ASD. The NOS3 G894 T polymorphism was associated with the risk of CHD in ethnic subgroup, increasing the risk of CHD in white race. Bioinformatics analysis did not find significant differences in NOS3 gene expression between individuals with TOF. The NOS3 G894 T (rs1799983) gene polymorphism is significantly associated with the risk of CHD, with notable variations in this association across different regions and ethnic groups. The T allele increases the risk of CHD by 31% compared to the G allele. Additionally, this polymorphism is linked to specific CHD subtypes, especially ASD.

PMID:40571825 | DOI:10.1007/s00210-025-04252-2

Cureus. 2025 May 26;17(5):e84818. doi: 10.7759/cureus.84818. eCollection 2025 May.

ABSTRACT

ST-elevation criteria miss a substantial number of acute coronary occlusions, resulting in treatment delays and worse prognosis. The Aslanger pattern has been proposed as a new pattern that, despite not meeting the definition of ST-elevation myocardial infarction, represents an acute coronary occlusion. Therefore, patients with this pattern could benefit from early revascularization. The case of a man with acute chest pain is presented, whose initial electrocardiogram showed an Aslanger pattern. Due to the misdiagnosis at the primary care center and the emergency room, the patient did not receive timely optimal management. This case remarks the importance of recognition of this new pattern and its impact on decision-making in patients with acute coronary syndrome.

PMID:40568275 | PMC:PMC12188695 | DOI:10.7759/cureus.84818

Med Sci Monit. 2025 Jun 15;31:e948085. doi: 10.12659/MSM.948085.

ABSTRACT

BACKGROUND Quantitative flow ratio (QFR) is a non-invasive angiographic tool that provides functional assessment of coronary stenosis without the need for pressure wires or hyperemia. This prospective study aimed to evaluate the procedural and inpatient treatment outcomes of QFR-guided percutaneous coronary intervention (PCI) compared with that of angiography-guided PCI in patients with ST-elevation myocardial infarction (STEMI) undergoing staged revascularization of non-culprit lesions. MATERIAL AND METHODS This randomized prospective single-center study was conducted at the Hospital of the Lithuanian University of Health Sciences Kaunas Clinics (July 2020-June 2021). After successful culprit-lesion PCI for STEMI, 124 participants with residual angiographically significant non-culprit stenosis (50-75%) were randomized to QFR-guided (n=62) or angiography-guided PCI (n=62). Procedural characteristics, fluoroscopy time, contrast usage, stent number/length, and inpatient treatment outcomes were compared between groups using SPSS 28.0 software. RESULTS Compared with PCI guided by visual estimation alone, the QFR-guided PCI group showed significant reductions in fluoroscopy time (median 6.2 vs 8.0 min, P=0.009), contrast volume (median 100 vs 120 mL, P=0.038), number of stents implanted (median 1.5 vs 2.0, P=0.002), and stent length (median 28 vs 45 mm, P<0.001). No significant differences were found between the groups in terms of periprocedural complications or length of inpatient stay. CONCLUSIONS QFR-guided PCI of the non-culprit lesion resulted in shorter fluoroscopy time, lower contrast volume, and a smaller number and average length of implanted stents. These findings highlight the potential of QFR to enhance procedural efficiency and reduce unnecessary stenting in clinical practice without compromising patient outcomes.

PMID:40566730 | PMC:PMC12178142 | DOI:10.12659/MSM.948085

Med Sci Monit. 2025 Jun 26;31:e948348. doi: 10.12659/MSM.948348.

ABSTRACT

BACKGROUND Many randomized controlled trials have explored the optimal revascularization strategy for patients with diabetes, but real-life outcomes are still poorly investigated. We assessed the complete 6-year outcomes of diabetic individuals with multivessel coronary artery disease (MVD) treated either with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). MATERIAL AND METHODS We reviewed data of all patients from 176 local Heart Team meetings and their treatment recommendations and assessed primary and secondary endpoints of 317 MVD patients with diabetes qualified either for CABG or PCI (98 and 219 patients, respectively) with subsequent optimal medical therapy. RESULTS At 6 years, no significant difference in overall mortality was observed (16.3% vs 20.5% for PCI, P=0.38). The incidence of myocardial infarction (MI) was higher in patients treated percutaneously (4.1% vs 12.3% for PCI, P=0.02), while those undergoing CABG had significantly longer postprocedural hospital stay (10.7 vs 4.4 days for PCI, P<0.01). The occurrence of major adverse cardiac and cerebrovascular events (MACCE), mainly driven by the increased rate of repeat revascularization (RR), was higher in the PCI group (83.6% vs 44.9%, P<0.01 and 47.0% vs 17.3%, P<0.01, respectively). The rates of stroke and in-hospital mortality were similar between the 2 groups. CONCLUSIONS For MVD patients with diabetes, CABG was superior in real-life clinical practice in terms of rates of MI, RR, and MACCE, while postprocedural hospital stays were shorted with PCI. The rates of all-cause death, stroke, and in-hospital mortality were comparable between groups.

PMID:40566650 | PMC:PMC12211400 | DOI:10.12659/MSM.948348

Life (Basel). 2025 Jun 4;15(6):908. doi: 10.3390/life15060908.

ABSTRACT

BACKGROUND: Matrix metalloproteinase 9 (MMP9) has recently emerged as a risk predictor in patients with cardiovascular diseases (CVD). However, little is known regarding the significance of elevated plasma MMP9 levels in patients during the long-term period following myocardial revascularisation. We aimed to investigate the role of MMP9 in relation to myocardial status before and after myocardial revascularisation and to assess its long-term prognostic value.

METHODS: This prospective observational study included 200 male patients with ischaemic heart disease. All patients underwent direct myocardial revascularisation on a beating heart (off-pump surgery). Plasma MMP9 levels were analysed preoperatively, at 48 h postoperatively, and during the long-term follow-up period (one year postoperatively). Key echocardiographic parameters, specifically left ventricular ejection fraction (LVEF) and Left Ventricular End-Diastolic Volume (LVEDV), were also assessed.

RESULTS: MMP9 levels decreased significantly at 48 h postoperatively (p < 0.0001). During the long-term postoperative period, a clear relationship was demonstrated: higher 1-year MMP9 levels were associated with lower 1-year LVEF, whilst lower 1-year MMP9 levels were associated with higher 1-year LVEF. No significant correlation was observed between preoperative MMP9 levels and age or most other baseline laboratory parameters.

CONCLUSIONS: Our study established an association between 1-year postoperative MMP9 levels and key parameters of left ventricular function during the long-term follow-up period. This suggests that MMP9 may serve as a novel biomarker for predicting outcomes following myocardial revascularisation.

PMID:40566560 | PMC:PMC12194191 | DOI:10.3390/life15060908

J Clin Med. 2025 Jun 17;14(12):4304. doi: 10.3390/jcm14124304.

ABSTRACT

Multiple sclerosis (MS) is a chronic progressive neurodegenerative disease that leads to disabilities such as difficulty moving and slowed cognitive processing. It is the leading non-traumatic cause of disability worldwide. MS also has a high potential to become a model for neurodegenerative diseases with a progression like Alzheimer's or Parkinson's. Cardiovascular diseases (CVDs) remain the leading cause of global deaths and have a considerable economic impact. The higher incidence of cardiovascular comorbidities in patients with MS compared to healthy individuals of the same age worsens the prognosis of neurological pathology, leading to a higher level of disability, poorer physical outcomes, higher depression scores, cognitive aging, and diminished quality of life. Classical observational studies often have questionable elements that can represent a source of error, making it difficult to establish a causal relationship between MS and CVD. Genetic studies, including genome-wide evaluation, may resolve this issue and may represent a topic for future research. We report the case of a 31-year-old male patient with a history of multiple sclerosis (MS) diagnosed seven years prior, who presented with acute chest pain upon returning from vacation. Despite the previous recommendation for disease-modifying therapy, the patient had discontinued treatment by personal choice. Electrocardiography (ECG) revealed ST-segment elevation in inferior leads, and emergent coronary angiography identified severe multi-vessel coronary artery disease (CAD), requiring immediate revascularization. This case highlights the potential cardiovascular risks in young patients with MS and the importance of continuous medical supervision.

PMID:40566048 | PMC:PMC12194425 | DOI:10.3390/jcm14124304

J Clin Med. 2025 Jun 12;14(12):4191. doi: 10.3390/jcm14124191.

ABSTRACT

Background/Objectives: The clinical implications of sarcopenia and visceral obesity in patients with cardiovascular disease (CVD) are poorly understood. We evaluated the impact of sarcopenia and visceral obesity on clinical outcomes among older adults with CVD. Methods: This retrospective cohort study included patients aged 65 years and older who had cardiovascular disease and had undergone body composition analysis using dual-energy X-ray absorptiometry (DXA) between November 2021 and October 2022 and been followed through February 2024. Sarcopenia was defined using the 2019 Asian Working Group for Sarcopenia criteria, and visceral obesity was defined using Korean sex-specific visceral adipose tissue area. The primary outcome was a composite of all-cause mortality and major cardiovascular events, including myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines. Results: A total of 317 patients were included, of whom 118 patients (37.2%) had sarcopenia, 184 (58.0%) had visceral obesity, and 55 (17.4%) had sarcopenic obesity. The prevalence of sarcopenia or visceral obesity was 93.8% in patients with obesity and 69.3% in those without obesity. Sarcopenic obesity showed a mixture of characteristics of two metabolic conditions in terms of demographics and body mass index. Sarcopenia was associated with an increased risk of primary outcomes (hazard ratio [HR], 1.93; 95% CI, 1.02-3.66), with the highest risk observed in patients with sarcopenic obesity (HR, 6.74; 95% CI, 1.81-25.16). Conclusions: Sarcopenia was associated with 1.9-fold increased risk of cardiovascular events among older adults with CVD, with a greater than 6-fold increased risk when combined with visceral obesity.

PMID:40565935 | PMC:PMC12194000 | DOI:10.3390/jcm14124191

J Clin Med. 2025 Jun 11;14(12):4130. doi: 10.3390/jcm14124130.

ABSTRACT

The current management of patients with acute coronary syndrome (ACS) and bleeding disorders, such as hemophilia, is supported by small retrospective studies or expert consensus documents. Moreover, people with hemophilia are less likely to receive invasive treatments like percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for ACS compared to those without hemophilia, which could affect their cardiovascular outcomes. A multidisciplinary team with an expert hematologist is essential to properly define the therapeutic strategy, which should balance both the thrombotic and bleeding risks. We report a clinical case that illustrates an alternative revascularization strategy for hemophilic patients presenting with ACS and with a pattern of diffuse coronary atherosclerotic disease (CAD), encompassing drug-coated balloons (DCBs) in combination with spot stenting. The proposed approach might avoid a full-length drug-eluting stent (DES) implantation and also allow a short dual antiplatelet therapy (DAPT) regimen that is desirable in patients at a very high bleeding risk (HBR) like hemophiliacs. Furthermore, we have provided a review of the available literature on this topic and a focus on the main recommendations for managing ACS, in response to the presented clinical case. Finally, this article aims to share information and develop more confidence in the current guidelines on the treatment of hemophiliacs who need myocardial revascularization.

PMID:40565875 | PMC:PMC12194593 | DOI:10.3390/jcm14124130

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 14;13(6):1470. doi: 10.3390/biomedicines13061470.

ABSTRACT

Background/Objectives: Polymer-free drug-eluting stents (PF-DESs) aim to mitigate long-term adverse effects associated with polymer-based platforms. However, clinical comparisons with biodegradable polymer DESs (BP-DESs) remain limited. The objective of this review is to assess the efficacy and safety of PF-DESs versus thin-struts (<100 μm) BP-DESs in patients undergoing percutaneous coronary intervention (PCI). Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PF-DESs and BP-DESs in adults undergoing PCI. PubMed, Embase, and CENTRAL were searched up to 1 February 2025. A random-effects model was used to calculate pooled risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). Outcomes included myocardial infarction (MI), all-cause and cardiac death, target lesion revascularization (TLR), stent thrombosis, and angiographic/OCT parameters. Subgroup and sensitivity analyses were conducted for outcomes with high heterogeneity (I2 > 50%). Results: Nine RCTs (n = 9597) were included. At 12 months, no significant differences were found between PF-DESs and BP-DESs for TLR (RR 1.51; 95% CI: 0.83-2.75), MI, or stent thrombosis. At 24 months, MI and all-cause death were similar between groups. A subgroup analysis showed lower cardiac death with the BioFreedom stent (RR 0.57; 95% CI: 0.35-0.90), not observed in non-BioFreedom devices. No significant differences were detected in angiographic or OCT outcomes, though heterogeneity was high. Conclusions: PF-DESs and BP-DESs demonstrated comparable clinical performance. The observed benefit in cardiac death with BioFreedom may reflect device-specific effects and merits further investigation.

PMID:40564189 | PMC:PMC12190656 | DOI:10.3390/biomedicines13061470

Biomedicines. 2025 May 23;13(6):1289. doi: 10.3390/biomedicines13061289.

ABSTRACT

Coronary microvascular disease (CMVD) is not an uncommon complication after acute myocardial infarction (AMI), independent of prompt revascularization. It is a serious yet underdiagnosed disease that has a major impact on patient outcomes. Even when the infarct-related artery is successfully revascularized, a significant percentage of patients still have compromised microvascular circulation, which is linked to higher cardiovascular mortality and hospitalization for heart failure. The well-known invasive methods, such as the index of microvascular resistance (IMR) and the coronary flow reserve (CFR), have been considered as gold standards. However, they are constrained by their hazards and complexity. Non-invasive techniques, such as echocardiography Doppler for CFR assessment, positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), and some other techniques provide alternatives, but their accessibility, cost and implementation during the peri-AMI period raise obstacles to their wider use. This review highlights both invasive and non-invasive modalities as it examines the diagnostic methods and prognostic significance of CMVD development early after AMI. Enhancing long-term results in this high-risk population requires a thorough understanding of pathophysiology and a commitment to larger diagnostic and prognostic studies for CMVD.

PMID:40564009 | PMC:PMC12189317 | DOI:10.3390/biomedicines13061289

Cardiol Rev. 2025 Jun 26. doi: 10.1097/CRD.0000000000000989. Online ahead of print.

ABSTRACT

Peripheral artery disease (PAD) is a severe manifestation of systemic atherosclerosis, affecting over 230 million individuals worldwide and leading to both limb-threatening ischemia and catastrophic cardiovascular events. This progression is driven in part by thrombosis, which arises from complex interactions of endothelial dysfunction, platelet activation, and thrombin generation. These processes culminate in acute limb ischemia, major amputations, and myocardial infarction. Antithrombotic therapy is fundamental to PAD management, with antiplatelet monotherapy (aspirin or clopidogrel) remaining first-line for symptomatic patients. However, the paradigm has shifted with dual-pathway inhibition (DPI), combining low-dose rivaroxaban (2.5 mg twice daily) with aspirin, which reduces major adverse cardiovascular events by 24% and limb events by 46%, particularly in high-risk subgroups including postrevascularization or chronic limb-threatening ischemia patients. Despite these advances, bleeding risks (eg, gastrointestinal hemorrhage with DPI) and global disparities in access to therapies pose significant challenges. Current guidelines now stratify recommendations by risk: the American Heart Association/American College of Cardiology endorses DPI for postrevascularization (class IIa), while the European Society of Cardiology reserves it for recurrent ischemia (class IIb). Emerging strategies target residual inflammatory risk (eg, colchicine) and vascular regeneration (stem cell therapy), yet cost and scalability limit widespread adoption, especially in developing nations bearing 70% of the PAD burden. The future of PAD care demands personalized approaches that integrate antithrombotic efficacy, bleeding mitigation, and socioeconomic realities. Further research is needed to refine risk stratification, expand access to DPI, and develop adjunctive therapies for this growing global health crisis.

PMID:40569059 | DOI:10.1097/CRD.0000000000000989

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

Br J Surg. 2025 May 31;112(6):znaf113. doi: 10.1093/bjs/znaf113.

NO ABSTRACT

PMID:40568914 | PMC:PMC12199258 | DOI:10.1093/bjs/znaf113