Basic Research in Cardiology最新文献

{"title":"Tyrosine phosphorylation of Kir6.2 subunit negatively regulates cardiac KATP channel activity","authors":"Yating Zhi, Bin Yang, Jianyi Huo, Haojie Wang, Bo Yang, Ya-Feng Zhou, Fei Xiao, Hua-Qian Yang","doi":"10.1007/s00395-025-01108-x","DOIUrl":"https://doi.org/10.1007/s00395-025-01108-x","url":null,"abstract":"<p>The plasma membrane ATP-sensitive potassium (K_ATP) channel in cardiac myocytes plays a critical role in protecting the heart against ischemic injury. Post-translational modifications regulate K_ATP channel activity and play a role in cardioprotection. However, the role of tyrosine phosphorylation in K_ATP channel regulation remains unclear. In this study, we investigated the cardiac K_ATP channel subtype Kir6.2/SUR2A and demonstrated that a protein tyrosine kinase inhibitor significantly increased the current amplitude through blunting the ATP sensitivity of K_ATP channels without altering the single-channel current or the channel surface expression. Mutation screening identified Y258 in the Kir6.2 subunit as the tyrosine phosphorylation site of the K_ATP channel. In cardiomyocytes, K_ATP channel currents can be reversibly enhanced or weakened by inhibiting the tyrosine kinase epidermal growth factor receptor or the protein tyrosine phosphatase 1B. Furthermore, in a perfused mouse heart model, the inhibitor of epidermal growth factor receptor exhibited a significant cardioprotective effect in a K_ATP channel dependent manner, indicating the pharmacological potential for treatment of ischemic heart disease.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"34 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of chronic hyperglycaemia on the coronary microcirculation – benefits of targeting IL-36 and diet reversal","authors":"Juma El-Awaisi, Dean Kavanagh, Silke Heising, Ina Maria Schiessl, Simon J. Cleary, David J. Hodson, Neena Kalia","doi":"10.1007/s00395-025-01107-y","DOIUrl":"https://doi.org/10.1007/s00395-025-01107-y","url":null,"abstract":"<p>Following myocardial infarction (MI), patients with type 2 diabetes mellitus (T2DM) have poorer prognosis which may be linked to increased susceptibility of coronary microvessels to injury. Interleukin-36 (IL-36) may mediate this injury but its role in the microcirculation of the chronically hyperglycaemic injured heart is unknown. Intravital and laser speckle imaging of the anaesthetised mouse beating heart evaluated the impact of a 16-week high fat diet (HFD)-induced hyperglycaemia ± myocardial ischaemia–reperfusion injury (IR) injury on coronary microvessels. Neutrophil/platelet recruitment, neutrophil extracellular trap formation, cellular necrosis, vascular leakage, vascular tonal changes, functional capillary density, overall ventricular perfusion and levels of circulating inflammatory cytokines were assessed alongside the vasculoprotective ability of an IL-36 receptor antagonist (IL-36Ra). Whether heightened microvessel damage in injured HFD mice was permanent or reversible was investigated after normalising hyperglycaemia through diet reversal (DR). Microcirculatory events assessed were perturbed basally in HFD mice and further after injury. IL-36Ra mitigated these effects and improved infarct size. DR was also beneficial, decreasing neutrophil recruitment to levels below those seen in untreated mice. Mechanistically, benefits of both IL-36Ra and DR could be explained by decreased endothelial oxidative stress and VCAM-1 expression and possibly by raised levels of IL-4/IL-13. Basal changes in chronically hyperglycaemic coronary microvessels that are heightened in the aftermath of reperfusion may explain the poorer outcomes in MI patients with T2DM. These findings are the first to highlight the specific benefits of IL-36 inhibition and reversing hyperglycaemia through dietary modification on the coronary microcirculation in a preclinical model of T2DM.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"26 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triiodothyronine protects infarcted myocardium by reducing apoptosis and preserving mitochondria","authors":"Domenico Cerullo, Polyxeni Mantzouratou, Angelo M. Lavecchia, Melissa Balsamo, Daniela Corna, Laura Brunelli, Christodoulos Xinaris","doi":"10.1007/s00395-025-01106-z","DOIUrl":"https://doi.org/10.1007/s00395-025-01106-z","url":null,"abstract":"<p>Myocardial infarction (MI) is a leading cause of heart failure, with thyroid hormone (TH) signaling playing a key role in heart function and postinfarct recovery. Despite evidence of TH administration's safety in cardiac patients, inconsistent therapeutic outcomes and limited understanding of its mechanisms hinder clinical translation. This study aims to investigate the long-term effect of acute triiodothyronine (T3) administration following MI and to elucidate the mechanisms of its cardioprotective actions. To this end, two doses (40 μg/kg) of T3 were administered immediately after injury and 24 h later in a cryoinjury mouse model of left ventricle (LV) infarction. Remarkably T3 administration significantly reduced scar expansion. Echocardiographic analysis conducted 28 days post-injury revealed that T3 administration improved LV remodeling and prevented LV hypertrophy. At molecular level, T3 administration strongly reduced apoptosis in the peri-infarcted area, without inducing cardiac cell proliferation. Furthermore, T3 prevented the accumulation of long-chain acylcarnitines and the subsequent mitochondrial damage. These findings demonstrate that acute T3 treatment following MI improves long-term LV function and reduces LV remodeling by limiting apoptosis in the peri-infarct region and by preserving mitochondrial function and structural integrity.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"23 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ketone body 3-hydroxybutyrate increases cardiac output and cardiac contractility in a porcine model of cardiogenic shock: a randomized, blinded, crossover trial","authors":"Oskar Kjærgaard Hørsdal, Alexander Møller Larsen, Kasper Lykke Wethelund, Frederik Flyvholm Dalsgaard, Jacob Marthinsen Seefeldt, Ole Kristian Lerche Helgestad, Niels Moeslund, Jacob Eifer Møller, Hanne Berg Ravn, Roni Ranghøj Nielsen, Henrik Wiggers, Kristoffer Berg-Hansen, Nigopan Gopalasingam","doi":"10.1007/s00395-025-01103-2","DOIUrl":"https://doi.org/10.1007/s00395-025-01103-2","url":null,"abstract":"<p>Cardiogenic shock (CS) is characterized by reduced cardiac output (CO), reduced end-organ perfusion, and high mortality. Medical therapies have failed to improve survival. The ketone body 3-hydroxybutyrate (3-OHB) enhances cardiac function in heart failure and CS. We aimed to elucidate the cardiovascular and cardiometabolic effects of 3-OHB treatment during CS. In a randomized, assessor-blinded crossover design, we studied 16 female pigs (60 kg, 5 months of age). CS was induced by left main coronary artery microsphere injections. Predefined criteria for CS were a 30% reduction in CO or mixed venous saturation (SvO₂). Intravenous 3-OHB infusion and a matching control solution were administered for 120 min in random order. Hemodynamic measurements were obtained by pulmonary artery catheterization and a left ventricular (LV) pressure–volume catheter. Myocardial mitochondrial function was assessed using high resolution respirometry. During CS, infusion with 3-OHB increased CO by 0.9 L/min (95%CI 0.4–1.3 L/min) compared with control infusion. SvO₂ (<i>P</i> = 0.026) and heart rate (<i>P</i> &lt; 0.001) increased. Stroke volume (<i>P</i> = 0.6) was not altered. LV contractile function as determined by LV end-systolic elastance improved during 3-OHB infusion compared with control infusion (<i>P</i> = 0.004). Systemic and pulmonary vascular resistance decreased, and diuresis increased. LV mitochondrial function was higher after 3-OHB infusion compared with control. We conclude that 3-OHB infusion enhances cardiac function by increasing contractility and reducing vascular resistance, while also preserving myocardial mitochondrial respiratory function in a large animal model of ischemic CS. These novel findings support the therapeutic potential of exogenous ketone supplementation in CS management.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"75 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical analysis of descriptive microRNA data in the translational research on cardioprotection and cardiac repair: lost in the complexity of bioinformatics","authors":"Mariann Gyöngyösi, Julia Guthrie, Ena Hasimbegovic, Emilie Han, Martin Riesenhuber, Kevin Hamzaraj, Jutta Bergler-Klein, Denise Traxler, Maximilian Y. Emmert, Matthias Hackl, Sophia Derdak, Dominika Lukovic","doi":"10.1007/s00395-025-01104-1","DOIUrl":"https://doi.org/10.1007/s00395-025-01104-1","url":null,"abstract":"<p>The unsuccessful translation of cardiac regeneration and cardioprotection from animal experiments to clinical applications in humans has raised the question of whether microRNA bioinformatics can narrow the gap between animal and human research outputs. We reviewed the literature for the period between 2000 and 2024 and found 178 microRNAs involved in cardioprotection and cardiac regeneration. On analyzing the orthologs and annotations, as well as downstream regulation, we observed species-specific differences in the diverse regulation of the microRNAs and related genes and transcriptomes, the influence of the experimental setting on the microRNA-guided biological responses, and database-specific bioinformatics results. We concluded that, in addition to reducing the number of in vivo experiments, following the 3R animal experiment rules, the bioinformatics approach allows the prediction of several currently unknown interactions between pathways, coding and non-coding genes, proteins, and downstream regulatory elements. However, a comprehensive analysis of the miRNA-mRNA-protein networks needs a profound bioinformatics and mathematical education and training to appropriately design an experimental study, select the right bioinformatics tool with programming language skills and understand and display the bioinformatics output of the results to translate the research data into clinical practice. In addition, using in-silico approaches, a risk of deviating from the in vivo processes exists, with adverse consequences on the translational research.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"43 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exendin-4 improves cerebral ischemia by relaxing microvessels, rapidly increasing cerebral blood flow after reperfusion","authors":"Yujie Chen, Lei Wang, Yutong Zhou, Yuguang Wang, Wei Qin, Mingxiao Wang, Bo Liu, Qian Tian, Huisen Xu, Hui Shen, Chen Zheng","doi":"10.1007/s00395-025-01096-y","DOIUrl":"https://doi.org/10.1007/s00395-025-01096-y","url":null,"abstract":"<p>Intravenous thrombolysis remains the cornerstone for restoring cerebral reperfusion post-stroke. Despite recombinant tissue plasminogen activator (rtPA) achieving arterial reperfusion within 6 h, persistent microcirculatory blood flow reduction often hampers recovery. Exendin-4, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has demonstrated potential for improving stroke outcomes, though its mechanisms remain partially unclear. This study investigated the role of Exendin-4 in restoring microcirculatory blood flow post-stroke. Using ischemic stroke models in 8-week-old male C57BL/6j mice, induced by transient middle cerebral artery occlusion or bilateral common carotid artery ligation, Exendin-4 (150 μg/kg) was administered intravenously. Infarct size and neurological deficits were evaluated using TTC staining and neurological severity scores. Real-time cerebral blood flow (CBF) and microvascular changes were measured with laser speckle imaging and two-photon microscopy. Mechanistic studies employed immunofluorescence and infrared differential interference contrast microscopy. Our findings demonstrated that Exendin-4 significantly reduced infarct size and improved neurological outcomes, independent of blood glucose levels. Immunofluorescence revealed GLP-1 receptor expression in arteriolar smooth muscle cells, endothelial cells, and pericytes. Exendin-4 enhanced microvascular blood flow via vasodilation, confirmed through real-time imaging. In vitro, Exendin-4 relaxed pre-constricted vessels, an effect that was abolished by eNOS and adenylate cyclase (AC) inhibitors. However, guanylate cyclase (GC) inhibition failed to block Exendin-4-induced vasodilation, suggesting a non-cGMP-dependent NO pathway may be involved. Furthermore, prostaglandin E2 (PGE2) signaling via EP4 receptors was identified as a critical contributor to Exendin-4’s vasodilatory effect, highlighting the involvement of multiple signaling pathways. These findings suggest that Exendin-4 preserves cerebral microcirculation through a multifaceted mechanism involving GLP-1R-mediated AC–cAMP signaling, PGE2–EP4 signaling, and a non-cGMP-dependent NO pathway. This study positions GLP-1 receptor agonists as promising therapeutic candidates for enhancing cerebral microcirculation and improving outcomes following stroke.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"70 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Necrosis-like cell death modes in heart failure: the influence of aetiology and the effects of RIP3 inhibition","authors":"Izabela Jarabicová, Csaba Horváth, Jaroslav Hrdlička, Almos Boroš, Veronika Olejníčková, Eva Zábrodská, Soňa Štemberková Hubáčková, Hana Mauer Šutovská, Ľuboš Molčan, Libor Kopkan, Martin Chudý, Branislav Kura, Barbora Kaločayová, Eva Goncalvesová, Jan Neckář, Michal Zeman, František Kolář, Adriana Adameová","doi":"10.1007/s00395-025-01101-4","DOIUrl":"https://doi.org/10.1007/s00395-025-01101-4","url":null,"abstract":"<p>Since cell dying in heart failure (HF) may vary based on the aetiology, we examined the main forms of regulated necrosis, such as necroptosis and pyroptosis, in the hearts damaged due to myocardial infarction (MI) or pressure overload. We also investigated the effects of a drug inhibiting RIP3, a proposed convergent point for both these necrosis-like cell death modes. In rat hearts, left ventricular function, remodelling, pro-cell death, and pro-inflammatory events were investigated, and the pharmacodynamic action of RIP3 inhibitor (GSK'872) was assessed. Regardless of the HF aetiology, the heart cells were dying due to necroptosis, albeit the upstream signals may be different. Pyroptosis was observed only in post-MI HF. The dysregulated miRNAs in post-MI hearts were accompanied by higher levels of a predicted target, HMGB1, its receptors (TLRs), as well as the exacerbation of inflammation likely originating from macrophages. The RIP3 inhibitor suppressed necroptosis, unlike pyroptosis, normalised the dysregulated miRNAs and tended to decrease collagen content and affect macrophage infiltration without affecting cardiac function or structure. The drug also mitigated the local heart inflammation and normalised the higher circulating HMGB1 in rats with post-MI HF. Elevated serum levels of HMGB1 were also detected in HF patients and positively correlated with C-reactive protein, highlighting pro-inflammatory axis. In conclusion, in MI-, but not pressure overload-induced HF, both necroptosis and pyroptosis operate and might underlie HF pathogenesis. The RIP3-targeting pharmacological intervention might protect the heart by preventing pro-death and pro-inflammatory mechanisms, however, additional strategies targeting multiple pro-death pathways may exhibit greater cardioprotection.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"23 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): a small animal acute myocardial infarction randomized-controlled multicenter study on the effect of ischemic preconditioning","authors":"Sauri Hernandez-Resendiz, Reinis Vilskersts, David Aluja, Ioanna Andreadou, Péter Bencsik, Maija Dambrova, Panagiotis Efentakis, Fei Gao, Zoltán Giricz, Javier Inserte, Roisin Kelly-Laubscher, Attila Kiss, Thomas Krieg, Brenda R. Kwak, Sandrine Lecour, Gary Lopaschuk, Michał Mączewski, Michał Waszkiewicz, Marta Oknińska, Pasquale Pagliaro, Bruno Podesser, Hiran A. Prag, Marisol Ruiz-Meana, Tamara Szabados, Coert J. Zuurbier, Péter Ferdinandy, Derek J. Hausenloy","doi":"10.1007/s00395-025-01102-3","DOIUrl":"https://doi.org/10.1007/s00395-025-01102-3","url":null,"abstract":"<p>Although many cardioprotective interventions have been shown to limit infarct size (IS), in preclinical animal studies of acute myocardial ischemia/reperfusion injury (IRI), their clinical translation to patient benefit has been largely disappointing. A major factor is the lack of rigor and reproducibility in the preclinical studies. To address this, we have established the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) small animal multisite acute myocardial infarction (AMI) network, with centralized randomization and blinded core laboratory IS analysis, and have validated the network using ischemic preconditioning (IPC). Eight sites from the COST Innovators Grant (IG16225) network participated in the IMPACT AMI study. Mice and rats were randomly allocated into Sham, Control, or IPC groups. The IRI group underwent 45 min (mice) or 30 min (rats) of left coronary artery occlusion followed by 24 h reperfusion. IPC comprised three cycles of 5 min occlusion/reperfusion before IRI. IS was determined by a blinded core lab. The majority of site showed significant cardioprotection with IPC. In pooled mouse data, IPC (<i>N</i> = 42) reduced IS/AAR by 35% compared to control (<i>N</i> = 48) (30 ± 16% versus 46 ± 13%; <i>p</i> &lt; 0.005), and in rat data, IPC (<i>N</i> = 36) reduced IS/AAR by 29% when compared to control (<i>N</i> = 39) (32 ± 19% versus 45 ± 14%; <i>p</i> &lt; 0.01). The IMPACT multisite mouse and rat AMI networks, with centralized randomization and blinded core IS analysis, were established to improve the reproducibility of cardioprotective interventions in preclinical studies and to facilitate the translation of these therapies for patient benefit.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"56 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing customized multivalent chemokine-binding peptide treatment in a murine model of coxsackievirus B3 myocarditis","authors":"Nicolas Kelm, Meike Kespohl, Gintare Smagurauskaite, Serena Vales, Kalimuthu Karuppanan, Philomena Mburu, Arne Thiele, Sandra Pinkert, Thomas Bukur, Michael Mülleder, Nikolaus Berndt, Karin Klingel, Matthias M. Gaida, Shoumo Bhattacharya, Antje Beling","doi":"10.1007/s00395-025-01098-w","DOIUrl":"https://doi.org/10.1007/s00395-025-01098-w","url":null,"abstract":"<p>Myocarditis, an inflammatory disease of the heart muscle, is often triggered by viral infections. This inflammation, which can lead to severe cardiac dysfunction and adverse outcomes, is mediated by various CC and CXC chemokines that interact with receptors in a “one-to-many” fashion. Ticks have evolved chemokine-binding salivary proteins known as Evasins, which efficiently suppress inflammation. This study explores a tailored Evasin-derived CC chemokine-targeting strategy using a 17-mer synthetic dimeric peptide, BK1.3. This peptide inhibits the inflammatory chemokines CCL2, CCL3, CCL7, and CCL8 in murine Coxsackievirus B3 (CVB3) infection, a viral trigger of myocarditis. Administered at a dose of 5 mg/kg twice daily, BK1.3 effectively maintains virus control without exacerbating CVB3-induced morbidity markers, such as hemodynamic compromise, multiorgan failure with hepatitis and pancreatitis, hypothermia, hypoglycemia, and weight loss. Metabolic profiling combined with proteomics reveals preserved reprogramming of lipid storage and gluconeogenesis capacity in the liver, alongside sustained energy production in the injured heart muscle. In survivors of acute CVB3 infection exhibiting manifestations of the subacute phase, BK1.3 enhances virus control, reduces myeloid cell infiltration in the heart and liver, improves markers of liver injury, and alleviates cardiac dysfunction, as evidenced by echocardiographic global longitudinal strain analysis. These findings affirm the safety profile of BK1.3 peptide therapeutics in a preclinical mouse model of acute CVB3 infection and emphasize its potential for therapeutic advancement in addressing virus-induced inflammation in the heart.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"27 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between female sex hormones, estrous cycle, ischemic preconditioning and myocardial infarct size after ischemia–reperfusion injury","authors":"Tetiana Pylova, Ahmed Elmahdy, Maryna Krasnikova, Abhishek Jha, Erik Axel Andersson, Yalda Kakaei, Aaron Shekka Espinosa, Amin Al-Awar, Ermir Zulfaj, Amirali Nejat, Valentyna Sevastianova, Mana Kalani, Henrik Ryberg, Åsa Tivesten, Elmir Omerovic, Björn Redfors","doi":"10.1007/s00395-025-01099-9","DOIUrl":"https://doi.org/10.1007/s00395-025-01099-9","url":null,"abstract":"<p>Studies on sex differences in myocardial infarction (MI) typically focus on males versus females, the exploration of hormonal physiologic variations and their impact on the infarct size remains limited. The objective of this study was to examine whether infarct size after myocardial ischemia/reperfusion injury in female rats differs in different phases of the estrous cycle, and according to the levels of sex hormones; and to assess whether the effect of ischemic preconditioning on infarct size varies in different phases of the estrous cycle and between sexes. Female rats were divided into three groups based on the estrous cycle: proestrus, estrus, and diestrus. A fourth group consisted of ovariectomized female rats. Male rats were included as a fifth group, and orchiectomized males as a sixth group. Each group underwent ischemia/reperfusion injury, with or without prior ischemic preconditioning (IPC). Plasma sex hormone levels were measured with gas chromatography-tandem mass spectrometry. Females in the proestrus showed significantly smaller infarct size compared to all other groups. Multivariable analyses identified proestrus, IPC, and estradiol as independent predictors of smaller infarct size while male sex and gonadectomy as independent predictors of larger infarct size. There was a statistical interaction between IPC and both sex and hormonal status, with a greater protective effect of IPC on infarct size in males and gonadectomized rats. After ischemia–reperfusion, proestrus female rats developed the smallest while male and gonadectomized rats the largest infarct size. Conversely, IPC conferred greater cardioprotection in male and gonadectomized rats than females in proestrus.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"7 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}