Cardiovasc Diabetol. 2025 Jun 23;24(1):260. doi: 10.1186/s12933-025-02822-5.
NO ABSTRACT
PMID:40551100 | PMC:PMC12183802 | DOI:10.1186/s12933-025-02822-5
Anal Bioanal Chem. 2025 Jun 23. doi: 10.1007/s00216-025-05969-y. Online ahead of print.
ABSTRACT
Diabetic cardiomyopathy (DCM), a cardiac complication of diabetes, is characterized by diastolic dysfunction, myocardial fibrosis, and structural remodeling. Carbonyl-containing metabolites (CCMs) play a critical role in driving DCM pathogenesis through metabolic dysfunction, oxidative stress, and lipid peroxidation. In this study, we employed an on-tissue chemical derivatization (OTCD)-based air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) approach to investigate spatial metabolic alterations of CCMs in the diabetic rat heart. This method enabled the spatial profiling of 369 CCMs-including 137 fatty aldehydes (FALs), 214 oxo fatty acids (OFAs), and 18 sterol-type lipids (STs)-across cardiac tissue sections. This expanded metabolite coverage revealed marked spatial heterogeneity in cardiac metabolism. Comparative analysis between diabetic and control rats identified 162 significantly altered CCMs, highlighting localized metabolic dysregulation associated with DCM. To explore potential therapeutic interventions, we further evaluated the metabolic impact of ferulic acid, a candidate agent for myocardial protection. High-dose ferulic acid treatment significantly modulated 43 differential CCMs, attenuated pyruvate accumulation, restored fatty aldehyde levels, and improved the profile of oxidized fatty acids. These findings suggest that ferulic acid ameliorates metabolic dysfunction by exerting antioxidant and anti-inflammatory effects, while enhancing mitochondrial function and lipid metabolism. Overall, this study demonstrates the utility of OTCD-AFADESI-MSI for spatially resolved metabolomic analysis of carbonyl stress in DCM and supports the therapeutic potential of ferulic acid in managing diabetic heart injury.
PMID:40551014 | DOI:10.1007/s00216-025-05969-y
BMJ Open. 2025 Jun 23;15(6):e096433. doi: 10.1136/bmjopen-2024-096433.
ABSTRACT
INTRODUCTION: Total hip arthroplasty (THA) is an effective treatment for severe osteoarthritis. However, THA has a high surgical risk for patients with concomitant diseases and is associated with several serious complications, such as myocardial infarction, acute kidney injury and cognitive dysfunction. This study will explore the potential protective effects of remote ischaemic preconditioning (RIPC) in cemented THA patients.
METHODS AND ANALYSIS: The PRINCIPAL study is designed as a randomised, controlled, parallel-group, blinded trial to assess the impact of RIPC in cemented THA patients. The study will compare two patient groups-one group will have the RIPC procedure, and the second will have the sham procedure. The primary outcome is the peak troponin T concentration during the three postoperative days. Secondary outcomes include markers of arterial stiffness (augmentation index (AIx), carotid-femoral pulse wave velocity, central blood pressures), neural (neuron-specific enolase, S100B) and renal injury biomarkers (estimated glomerular filtration rate, creatinine, cystatin C), markers of systemic inflammation (hypoxia-inducible factor 1-alpha, interleukin (IL)-6, IL-1β, tumour necrosis factor-alpha, IL-10) and oxidative stress (total peroxide concentration, total antioxidant capacity), as well as clinical outcome measures such as major adverse cardiovascular events and all-cause mortality.
ETHICS AND DISSEMINATION: The ethical board of the University of Tartu has granted approval for the study (no. 384T-26). The results of this study will be disseminated in international peer-reviewed journals.
TRIAL REGISTRATION NUMBER: NCT06323018.
PMID:40550717 | PMC:PMC12186052 | DOI:10.1136/bmjopen-2024-096433
Circulation. 2025 Jun 24;151(25):e1093-e1094. doi: 10.1161/CIRCULATIONAHA.125.074590. Epub 2025 Jun 23.
NO ABSTRACT
PMID:40549847 | DOI:10.1161/CIRCULATIONAHA.125.074590
Circulation. 2025 Jun 24;151(25):e1091-e1092. doi: 10.1161/CIRCULATIONAHA.124.072438. Epub 2025 Jun 23.
NO ABSTRACT
PMID:40549843 | DOI:10.1161/CIRCULATIONAHA.124.072438
World J Diabetes. 2025 Jun 15;16(6):103685. doi: 10.4239/wjd.v16.i6.103685.
ABSTRACT
BACKGROUND: Erianin is a natural bibenzyl compound extracted from Dendrobium chrysotoxum and is known for its anti-inflammatory and antioxidant properties.
AIM: To explore the possible therapeutic mechanisms of erianin and determine if it can reduce cardiac damage in mice with type 2 diabetes.
METHODS: High-fat diet and intraperitoneal injections of streptozotocin were used to induce type 2 diabetes mellitus in C57BL/6 mice. Mice were divided into different groups including control, model, and treatment with various doses of erianin (10, 20, and 40 mg/kg) as well as ML-385 + erianin group.
RESULTS: Erianin reduced oxidative stress and inflammation and alleviated diabetic cardiomyopathy through the activation of the adenosine monophosphate-activated protein kinase (AMPK)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) pathway. Treatments with erianin-M and erianin-H promoted weight stabilization and normalized fasting glucose levels relative to diabetic controls. Echocardiographic assessment demonstrated that erianin dose-dependently enhanced left ventricular systolic function (left ventricular ejection fraction, left ventricular fractional shortening) and mitigated ventricular remodeling (left ventricular internal diameter at end-diastole, left ventricular internal diameter at end-systole; P < 0.05 vs model group). No significant differences were observed between the ML-385 + erianin and placebo-treated groups. Histopathological examination through hematoxylin-eosin staining indicated that erianin ameliorated myocardial fiber fragmentation, structural disorganization, inflammatory cell infiltration, and cytolytic damage. Furthermore, it significantly reduced the serum levels of cardiac troponin I, creatine kinase, and its MB isoenzyme. However, the ML-385 + erianin co-treatment failed to alleviate myocardial injury. Metabolic profiling revealed erianin-mediated improvements in glycemic regulation (glycated hemoglobin: P < 0.001), plasma insulin homeostasis, and lipid metabolism (total cholesterol, triglycerides, low-density lipoprotein cholesterol reduction, and high-density lipoprotein cholesterol restoration; P < 0.05 vs model group). Proinflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were markedly suppressed in the erianin-M and erianin-H groups compared with the model group, whereas no significant differences were detected between the model and ML-385 + erianin groups. Oxidative stress parameters showed decreased malondialdehyde levels accompanied by elevated superoxide dismutase and catalase activities in erianin-treated groups, with the most pronounced effects in the erianin-H group (P < 0.05). Western blot analysis confirmed the significant upregulation of proteins associated with the AMPK/Nrf2/HO-1 pathway in erianin-M and erianin-H groups. These protective effects were abolished in the ML-385 + erianin co-treatment group, which showed no statistical differences from the model group.
CONCLUSION: Erianin can effectively alleviate myocardial injury in type 2 diabetic mice by activating the AMPK-Nrf2-HO-1 pathway.
PMID:40548264 | PMC:PMC12179885 | DOI:10.4239/wjd.v16.i6.103685
Adv Sci (Weinh). 2025 Jun 23:e08673. doi: 10.1002/advs.202508673. Online ahead of print.
ABSTRACT
Mitochondrial dysfunction is related to etiopathogenesis and progression of heart failure (HF). The underlying molecular mechanisms are not fully understood. Transcription factor FOXM1 plays an essential role in cardiovascular development. The present study explores its role in mitochondrial bioenergetics in postmitotic cardiomyocytes (CMs). FOXM1 is significantly upregulated in ischemic heart tissues from humans, mice, and pigs. CM-specific Foxm1-knockout mice exhibit dilated cardiomyopathy features associated with mitochondrial dysfunction. Transcriptomic and proteomic profiling of Foxm1-knockout mice reveal robust, specific downregulation of gene programs important for mitochondrial energetics and homeostasis. Analysis of proteome and ubiquitinome data reveal that FOXM1 deficiency in CMs promotes LKB1 ubiquitination and impairs the AMPK signaling and energy metabolism pathways. Bioinformatics analysis identifies that E3 ligase MKRN1 promotes the K48-linked ubiquitination of LKB1 on Lys146, which in turn, inhibits the AMPK signaling pathway and impairs energy homeostasis in mice with HF. CM-specific Mkrn1 knockout ameliorates cardiac dysfunction by rejuvenating the impaired mitochondrial bioenergetics induced by FOXM1 deficiency. FOXM1 overexpression preserves mitochondrial bioenergetics and protects against myocardial I/R injury in both rodent and porcine models. In conclusion, FOXM1 is actively involved in mitochondrial bioenergetics during HF. FOXM1 may be a potential promising therapeutic target for myocardial I/R injury and HF.
PMID:40546121 | DOI:10.1002/advs.202508673
Toxicol Appl Pharmacol. 2025 Jun 20;502:117448. doi: 10.1016/j.taap.2025.117448. Online ahead of print.
ABSTRACT
Pyroptosis is one of the major forms of cardiomyocyte death following ischemia/reperfusion (I/R). Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1)/Tumor necrosis factor receptor associated factor 6 (TRAF6) pathway is involved in cardiomyocyte pyroptosis in mouse heart following I/R, and telaprevir, a hepatitis C virus protease inhibitor, has been predicted as a potential inhibitor of MALT1. This study aims to explore the effect of telaprevir on I/R-induced cardiomyocyte pyroptosis. The C57BL/6J mouse was subjected to 45 min-ischemia plus 24 h-reperfusion to establish the myocardial I/R injury model, while H9c2 cardiomyocytes were exposed to hypoxia for 8 h plus reoxygenation for 24 h (H/R) to simulate the I/R pathological process in vitro. Compared to the control group, pyroptosis was significantly increased in the I/R-treated mouse heart or the H/R-treated cardiomyocytes, evidenced by the elevated GSDMD and caspase-11 cleavage. Compared to the vehicle, telaprevir reduced myocardial infarcted size and cleavage of caspase-11 and gasdermin D (GSDMD) in mouse heart following I/R and cultured cardiomyocytes subjected to H/R in a dose-dependent manner. Mechanistically, telaprevir inhibited the recruitment of TRAF6 by MALT1, concomitant with the reduced recruitment of caspase-11 by TRAF6, and in turn, attenuated caspase-11 K63 poly-ubiquitination and activation, which was further confirmed by knockdown of TRAF6. Based on these results, we concluded that telaprevir could protect mouse heart against I/R injury by reducing caspase-11-dependent pyroptosis through inhibition of MALT1/TRAF6 pathway.
PMID:40545203 | DOI:10.1016/j.taap.2025.117448
Cell Signal. 2025 Jun 20;134:111956. doi: 10.1016/j.cellsig.2025.111956. Online ahead of print.
ABSTRACT
Endogenous ghrelin and its synthetic mimetics are peptide growth hormone (GH) secretagogues (GHSs) that exert a variety of cardioprotective effects. There are experimental evidence suggesting the beneficial effects of GHSs on ischemia/ reperfusion (I/R) injury, myocardial infarction (MI), heart failure (HF), isoproterenol-induced injury, and doxorubicin-induced cardiotoxicity. The effects of GHS were mediated by improving contractility and cardiac output, vasodilation, boosting cardiac antioxidant potential, reducing infarct size, and inhibition of cardiac apoptosis and fibrosis. The existing literatures have confirmed the improvement of cardiac function, attenuation of inflammation, rebalancing the autonomic nervous system (ANS), suppression of cardiac remodeling, improving arrhythmia and HF by GHS in experimental animal models and clinical patients. However, the molecular mechanisms of GHS on HF have not been fully elucidated. Here, we summarize available recent data on improving HF by GHS through molecular signaling pathways, to propose a novel strategy for the prevention and treatment of HF.
PMID:40545112 | DOI:10.1016/j.cellsig.2025.111956
Metabolism. 2025 Jun 19;170:156332. doi: 10.1016/j.metabol.2025.156332. Online ahead of print.
ABSTRACT
Cardiovascular diseases (CVDs), the leading cause of global mortality, are now understood to be profoundly influenced by the endocrine regulatory functions of the skeletal system. Emerging evidence suggests that osteocrine factors, including fibroblast growth factor-23 (FGF23), lipocalin-2 (LCN2), Dickkopf-1 (DKK1), myeloid-derived growth factor (MYDGF), osteocalcin (OCN), and sclerostin (SOST), establish bidirectional regulatory networks with the cardiovascular system, termed the "bone-heart axis". This axis regulates critical pathological processes, including mineral metabolism, vascular calcification, and myocardial energy homeostasis. Dysregulation of this crosstalk accelerates the progression of atherosclerosis (AS), heart failure (HF), and other CVDs. Therefore, current research necessitates a paradigm shift from univariate analyses to elucidating the spatiotemporal dynamics of interorgan communication, thereby facilitating the development of precision therapeutic strategies for integrated skeletal and cardiovascular protection.
PMID:40543811 | DOI:10.1016/j.metabol.2025.156332
Mol Med Rep. 2025 Sep;32(3):232. doi: 10.3892/mmr.2025.13597. Epub 2025 Jun 20.
ABSTRACT
The present study aimed to identify differentially expressed circRNAs in hypertrophic cardiac tissues and explored the potential regulatory role and mechanism of one differentially expressed circRNA in myocardial hypertrophy. RNA sequencing was used to identify differentially expressed circRNAs in hypertrophic and control cardiac tissues. CircRNA expression levels were verified by reverse transcription‑quantitative PCR. Isoproterenol (ISO) was used to induce hypertrophy of AC16 cells. The extent of cell hypertrophy was indicated by the cell size, protein/DNA ratio and levels of B‑type natriuretic peptide (BNP) and β‑myosin heavy chain (β‑MHC). The interactions between hsa_circ_0072107 and miR‑516b‑5p, as well as between miR‑516b‑5p and zinc ring finger protein 36 (ZFP36), were confirmed through dual luciferase assays, biotinylated probe pull‑down and anti‑AGO2 RNA immunoprecipitation assays. hsa_circ_0072107 was one of the most upregulated circRNAs in hypertrophic cardiac tissues. hsa_circ_0072107 overexpression and ISO treatment increased cell size, elevated the protein/DNA ratio and increased the levels of BNP and β‑MHC in AC16 cells, indicating that hsa_circ_0072107 aggravates AC16 hypertrophy. These changes induced by ISO treatment could be blocked by the knockdown of hsa_circ_0072107. The dual‑luciferase activity assay indicated that miR‑516b‑5p can bind to hsa_circ_0072107. miR‑516b‑5p binding site mutation blocked the effect of hsa_circ_0072107. ZFP36 is a target gene of miR‑516b‑5p, which suppresses AC16 hypertrophy. hsa_circ_0072107 overexpression alleviated the effect of miR‑516b‑5p overexpression on cell hypertrophy and ZFP36 expression. hsa_circ_0072107 is up‑regulated in hypertrophic cardiac tissues and potentially promotes AC16 hypertrophy and may play its role by acting as a competitive endogenous RNA of miR‑516b‑5p. Thus, hsa_circ_0072107 may be a novel target for the treatment of myocardial hypertrophy.
PMID:40539438 | DOI:10.3892/mmr.2025.13597
Physiol Rep. 2025 Jun;13(12):e70425. doi: 10.14814/phy2.70425.
ABSTRACT
This study aims at defining a standardized workflow based on a customized ImageJ macro combined with a machine-learning algorithm to analyze morphometric features of isolated cardiomyocytes using high-resolution/high-content photomicrographs and to identify key and specific morphological features of cardiomyocytes isolated from various murine cardiac hypertrophy models. For that purpose, we set up and optimized a Langendorff based protocol for isolating cardiomyocytes from mouse hearts. This optimized protocol yielded in a significantly high number of formaldehyde-fixed cardiomyocytes, with more than 97% of rod shaped cells. Moreover, our method allowed for reliable gene expression analysis and conservation of cell integrity through multiple freeze-thaw cycles. Next, we successfully applied our analytical workflow on formaldehyde-fixed cardiomyocytes isolated from various murine cardiac hypertrophy models and defined distinct morphological features in Angiotensin II, Isoproterenol, and age-induced hypertrophy. Taken together, our study provides an effective and standardized workflow for high-throughput morphological and molecular characterization of isolated cardiomyocytes, and could constitute a robust and reliable analytical tool to distinguish healthy versus diseased states and assess the ability of a potential therapeutic agent or strategy to reverse the situation.
PMID:40538075 | PMC:PMC12179408 | DOI:10.14814/phy2.70425
Sci Rep. 2025 Jun 20;15(1):20195. doi: 10.1038/s41598-025-06206-3.
ABSTRACT
Acute myocardial infarction (MI), a serious manifestation of ischemic heart disease, remains the culprit for mortality among coronary heart disease patients. Astaxanthin has demonstrated the ability to alleviate inflammation-induced myocardial damage while maintaining a balance between oxidants and antioxidants. This study investigates the cardioprotective potential of astaxanthin (ASX), particularly when encapsulated in nanostructured lipid carriers (NLCs), in isoprenaline (ISO)-induced myocardial infarction in rats. The study involved 48 rats separated into 6 groups. ASX and Nano-ASX (5 mg/kg) were administrated orally for 21 days before MI induction (isoprenaline, 85 mg/kg, subcutaneously). Blood and cardiac tissue samples were taken 24 h following the last isoprenaline injection for biochemical and histopathological investigation. The findings reveal that nano-formulated ASX significantly reduces oxidative stress and cardiac injury markers, including CK-MB, Troponin-I, and LDH. Additionally, it enhances antioxidant enzyme activities (GSH, GPx, and GSH-RD) and decreases inflammatory markers (COX-2 and VEGF). The study further demonstrates that nano-ASX stimulates autophagy by upregulating critical genes such as Beclin-1, ULK1, and LC3B, which are vital for cardiac protection and repair. Histological analysis confirms these biochemical outcomes, showing reduced myocardial damage and inflammation in the nano-ASX-treated groups. This study concludes the potential of ASX nano-formulations as an advanced therapeutic approach for myocardial infarction, leveraging improved bioavailability and targeting oxidative stress, inflammation, and autophagic mechanisms.
PMID:40542058 | PMC:PMC12181253 | DOI:10.1038/s41598-025-06206-3
Chem Biol Interact. 2025 Jun 18;418:111607. doi: 10.1016/j.cbi.2025.111607. Online ahead of print.
ABSTRACT
Myocardial ischemia can induce myocardial infarction, posing a severe threat to human health. Although restoration of blood and oxygen supply alleviates tissue damage and reduces infarct size, reperfusion may trigger additional injury that exacerbates myocardial structural and functional disturbances, a phenomenon termed myocardial ischemia-reperfusion injury (MIRI). Ginkgolide B (GB), a terpenoid compound extracted from Ginkgo biloba leaves, exhibits cardiovascular protective properties. This study investigates the potential anti-MIRI effects of GB, with specific emphasis on elucidating the role of the GAS6/Axl signaling pathway in its cardioprotective mechanisms. In vivo experiments demonstrated that GB improved cardiac function and serum biochemical parameters in mice, concurrently suppressing apoptosis and mitigating oxidative stress. In vitro studies further revealed that GB protected HL-1 cardiomyocytes from hypoxia-reoxygenation (HR) injury, as evidenced by enhanced cell viability, reduced apoptosis rates, decreased ROS and LDH levels, alongside upregulated expression of GAS6, Axl, Bcl2, antioxidant-related proteins, and mitochondrial function-associated proteins. Crucially, the protective effects of GB were reversed by GAS6 knockdown or genetic ablation in the HL-1 cell HR model. Collectively, this study confirms the definitive cardioprotective efficacy of GB against MIRI and delineates the critical involvement of the GAS6/Axl signaling pathway, thereby establishing a robust theoretical foundation and scientific rationale for the clinical application of GB in MIRI management.
PMID:40541647 | DOI:10.1016/j.cbi.2025.111607
Cardiovasc Revasc Med. 2025 May 30:S1553-8389(25)00284-2. doi: 10.1016/j.carrev.2025.05.031. Online ahead of print.
ABSTRACT
BACKGROUND: High-risk percutaneous coronary intervention (HRPCI) procedures supported by percutaneous left ventricular assist devices (pLVAD) are increasingly common, but existing PCI risk scores were developed in patients across the risk spectrum, including few pLVAD-assisted patients.
OBJECTIVES: Assess the performance of existing PCI risk scores in patients receiving pLVAD-assisted HRPCI and create a novel risk score specific to this group.
METHODS: Patients in the PROTECT III multicenter, observational (46 US centers) study undergoing pLVAD-assisted HRPCI were assessed. The National Cardiovascular Data Registry (NCDR) bedside risk score and the Complex High-Risk Indicated PCI (CHIP-PCI) risk score were calculated for each patient, and their accuracy in predicting in-hospital events was assessed. A novel risk score for in-hospital mortality was created using pre-procedural variables which were significant in univariable and multivariable regressions.
RESULTS: Among 1237 patients, the NCDR bedside risk score showed modest discrimination (C-index 0.71) but poor goodness of fit (R2 = 0.30). The CHIP-PCI score had poor discrimination (C-index 0.61) and reasonable goodness of fit (R2 = 0.62). Five independent predictors of in-hospital mortality were identified: age >80 years, eGFR <30, left main disease, acute myocardial infarction, and left ventricular ejection fraction <30 %. These formed the "HRPCI" risk score (C-index 0.75), which correlated with 30-day mortality (5.4 % vs. 17.0 %, p<0.0001).
CONCLUSIONS: Existing PCI risk scores perform poorly in patients undergoing pLVAD-assisted HRPCI. A novel easily, calculable HRPCI risk score can assist in clinical decision making once validated.
CLINICAL TRIAL INFORMATION: Trial Name: The Global cVAD Study (cVAD). URL: https://clinicaltrials.gov/ct2/show/NCT04136392?term=cvad&draw=2&rank=2 ClinicalTrial.gov Identifier: NCT04136392.
PMID:40541479 | DOI:10.1016/j.carrev.2025.05.031
FASEB J. 2025 Jun 30;39(12):e70734. doi: 10.1096/fj.202402897RR.
ABSTRACT
ELABELA (ELA) has been identified as a potential cardiovascular protective factor. However, the source of endogenous ELA and its molecular mechanism in myocardial fibrosis inhibition remain incompletely understood. Herein, we found that aerobic exercise significantly improved renal apoptosis caused by MI, inhibited inflammation, attenuated structural damage, enhanced renal function, and increased expression and secretion levels of renal ELA. Aerobic exercise stimulated the circulation of renal-derived ELA to reach the MI heart and played a protective role. Under aerobic exercise intervention, renal-specific Elabela overexpression improved myocardial pathological remodeling, decreased cardiomyocyte apoptosis, and enhanced cardiac function. Renal-specific Elabela knockdown significantly increased cardiac apoptosis, inflammation, and fibrosis levels in MI mice, leading to severe impairment of cardiac function. Following AMPK agonist intervention, ELA expression in HKC cells and culture medium increased in a concentration-dependent manner. ELA-14 significantly activated the APJ-AMPK-Sirt1 signaling pathway and inhibited Tgf-β1 transcription by regulating Sirt1 translocation, and AMPK inhibitor weakened ELA-14 function. In cultured cardiac fibroblasts (CFs), the intervention of ELA-14 significantly inhibited the activity of the TGFβ1-Smad2/3 signaling pathway, downregulated the expression of fibrosis-related proteins, increased apoptosis, and lowered the cell migration rate. After TGFβR1 inhibitor intervention, ELA-14 showed a loss of regulation of CFs. Aerobic exercise stimulates the expression of renal-derived ELA, which reaches the MI heart through blood circulation. Renal-derived ELA partly exerts its antifibrotic effects by activating the APJ-AMPK-Sirt1 pathway and inhibiting the TGFβ1-Smad2/3 signaling pathway, contributing to its cardiac protective effects.
PMID:40540261 | DOI:10.1096/fj.202402897RR
Cardiol Rev. 2025 Jun 20. doi: 10.1097/CRD.0000000000000971. Online ahead of print.
ABSTRACT
Dual antiplatelet therapy is a standard treatment after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS), but the optimal monotherapy agent post-dual antiplatelet therapy remains unclear. Clopidogrel and aspirin are widely used, yet their comparative effectiveness and safety in this patient population have not been fully established. This systematic review and meta-analysis compared the efficacy and safety of clopidogrel and aspirin monotherapy following PCI in patients with ACS. A comprehensive search of PubMed, Embase, and Web of Science was conducted from inception to March 31, 2025. Randomized controlled trials (RCTs) comparing clopidogrel and aspirin monotherapy in adult ACS patients post-PCI were included. Primary outcomes were all-cause death, myocardial infarction (MI), and ischemic stroke. Secondary outcomes included target-vessel and target-lesion revascularization, cardiovascular and noncardiovascular death, and stent thrombosis. The risk of bias was assessed using the Cochrane RoB 2 tool, and the GRADE methodology was applied to evaluate the certainty of evidence. Three RCTs involving 16,056 patients (clopidogrel: 8103; aspirin: 7953) were included. Clopidogrel significantly reduced MI (risk ratio = 0.71; 95% confidence interval: 0.55-0.92; P = 0.01) and target-vessel revascularization (risk ratio = 0.77; 95% confidence interval: 0.60-0.97; P = 0.03). No significant differences were found in all-cause death, ischemic stroke, or other secondary outcomes. Sensitivity analysis suggested a potential reduction in noncardiovascular death favoring clopidogrel. Clopidogrel monotherapy after PCI may offer superior protection against MI and target-vessel revascularization compared with aspirin, with no increased risk of death or stroke.
PMID:40539811 | DOI:10.1097/CRD.0000000000000971
Cytojournal. 2025 May 6;22:49. doi: 10.25259/Cytojournal_12_2025. eCollection 2025.
ABSTRACT
OBJECTIVE: Ischemia-reperfusion (I-R) injury in the myocardium is a considerable challenge in cardiovascular medicine, posing a severe threat to life. Given that galectin-3 possibly regulates myocardial I-R damage, this study aims to investigate the detailed mechanisms underlying galectin-3's effects on myocardial I-R injury.
MATERIAL AND METHODS: The expression levels of galectin-3 in vivo and in vitro myocardial I-R models were determined by Western blot and quantitative real-time polymerase chain reaction. The effects of galectin-3 on inflammatory factors and oxidative stress factors in myocardial I-R were measured with an enzyme-linked immunosorbent assay, and the extent of myocardial tissue damage was assessed using hematoxylin-eosin staining. The influence of galectin-3 on peroxisome proliferator-activated receptor g (PPARg) signaling pathway-related proteins in myocardial I-R was determined by Western blot.
RESULTS: Myocardial I-R damage was associated with increased galectin-3 expression, and the blood levels of creatine kinase-myocardial band and creatine kinase were favorably correlated with the messenger RNA levels of galectin-3 in mice with cardiac I-R damage. The inhibition of galectin-3 alleviated oxidative stress and inflammatory response, and galectin-3 promoted reactive oxygen species production in myocardial I-R cells. Furthermore, the cardiac I-R damage mouse model exhibited decreased expression of proteins linked to the PPARg signaling pathway, but galectin-3 inhibition enhanced the expression of these proteins.
CONCLUSION: Galectin-3 plays a crucial role in exacerbating myocardial I-R injury, and its up-regulation is associated with increased oxidative stress, inflammatory responses, and inhibition of the protective PPARg signaling pathway. The alleviation of these harmful effects by galectin-3 inhibition suggests that targeting galectin-3 is a potential therapeutic method for reducing myocardial I-R injury.
PMID:40539121 | PMC:PMC12178088 | DOI:10.25259/Cytojournal_12_2025
Front Pharmacol. 2025 Jun 5;16:1516836. doi: 10.3389/fphar.2025.1516836. eCollection 2025.
ABSTRACT
INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and disability globally. Several studies have shown that 5-lipoxygenase (5-LOX) inhibition reduces leukotriene (LT) release and the inflammatory response, attenuating the development of respiratory diseases, myocardial infarction, and ischemic cerebral injury. However, its role in the pathophysiology of TBI remains unclear.
METHODS: Controlled cortical impact injury was induced to construct a mouse model of TBI. Pericontusional brain tissue samples from sham and TBI mice at 7 days after injury were used for RNA-seq analysis. Altered gene enrichment following TBI, based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, was quantified through real-time polymerase chain reaction (RT-PCR). Immunocytochemistry, Western blotting, and single-cell sequencing experiments were also performed to analyze 5-Lox protein expression. Arachidonic acid (AA) was detected through liquid chromatography mass spectrometry/mass spectrometry. Enzyme-linked immunosorbent assay was used to detect LTB4 release after TBI with or without zileuton treatment. Brain damage, blood-brain barrier disruption, and neuronal apoptosis were detected through histological examination. Neurological outcomes were determined through rotarod and fear conditioning tests.
RESULTS: TBI induced significant upregulation of genes related to the AA metabolic pathway, particularly the AA/5-LOX/LT axis, as verified by RT-PCR. AA and LTB4 production increased significantly after TBI. The expression levels of Pla2g4a, which hydrolyses phospholipids to release AA, and 5-Lox, which in turn act downstream to convert AA to LT, were dramatically upregulated up to 7 days after TBI. 5-LOX accumulated in the cytoplasm of activated ameboid microglial cells. In vivo, 5-LOX inhibition with zileuton blocked LT release and reduced microglial activation and the production of inflammatory cytokines, including Il-1β, Ccl7, Spp1, Ccr1, Ccl2, and Il-10. Zileuton also reduced TBI-induced lipid ROS and neuronal cell apoptosis, ameliorating brain damage compared to the vehicle group and improving neurological outcomes after TBI. Mechanically, TBI-induced LT upregulation may stimulate BV2 microglial activation through the ERK, NF-κB, and Akt pathways.
CONCLUSION: Our findings demonstrated the role of 5-LOX in TBI and its potential as a therapeutic target in TBI treatment.
PMID:40538546 | PMC:PMC12176805 | DOI:10.3389/fphar.2025.1516836
IUBMB Life. 2025 Jun;77(6):e70035. doi: 10.1002/iub.70035.
ABSTRACT
Peroxisome proliferator-activated receptors (PPARs), particularly PPAR-α and PPAR-γ, are key regulators of cardiac energy metabolism and have been implicated in cardiac remodeling. However, their roles in cardiomyocyte proliferation and hypertrophy remain incompletely understood. In this study, we investigated the effects of PPAR-α and PPAR-γ modulation on neonatal rat cardiomyocytes (NRCMs) using pharmacological agonists (WY-14643 for PPAR-α and pioglitazone for PPAR-γ) and inhibitors (MK-886 for PPAR-α and GW9662 for PPAR-γ), as well as siRNA-mediated knockdown approaches. Cardiomyocyte proliferation and hypertrophy were assessed by immunofluorescence, cell size measurements, and proliferation assays. Our findings demonstrate that PPAR-α activation significantly promotes cardiomyocyte proliferation and reduces hypertrophy, whereas PPAR-α inhibition induces hypertrophic changes and suppresses proliferation. Similarly, PPAR-γ activation enhances both proliferation and hypertrophy of cardiomyocytes, suggesting its involvement in physiological hypertrophy and a potential protective role in pathological remodeling. In contrast, pharmacological activation or genetic inhibition of PPAR-δ showed no significant effects on cardiomyocyte proliferation or hypertrophy, highlighting its distinct role in metabolic homeostasis rather than structural remodeling. PPAR-α and PPAR-γ play distinct but complementary roles in regulating cardiomyocyte proliferation and hypertrophy. These results suggest that targeting PPAR-α and PPAR-γ may represent promising therapeutic strategies for cardiac hypertrophy and heart failure. Further in vivo studies are warranted to clarify their molecular mechanisms and potential clinical applications.
PMID:40536211 | DOI:10.1002/iub.70035