Basic Research in Cardiology最新文献

{"title":"Chemokine-receptor-guided B-cell immunity in cardiovascular disease.","authors":"Anais Yerly,Emiel P C van der Vorst,Marc Schindewolf,Drosos Kotelis,Heidi Noels,Yvonne Döring","doi":"10.1007/s00395-025-01140-x","DOIUrl":"https://doi.org/10.1007/s00395-025-01140-x","url":null,"abstract":"Cardiovascular diseases (CVD) include a wide range of disorders affecting the heart and blood vessels, many of which are associated with atherosclerosis. Atherosclerosis is the main underlying cause of CVDs and represents a chronic inflammatory disease of the large arteries involving the build-up of plaques within the arterial wall. B cells play a dual role in CVD, particularly in the context of atherosclerosis, by producing antibodies and secreting cytokines that modulate inflammation. Depending on their subtype (B1 vs. B2 cells) and the specific context, B cells can have both protective and harmful effects on the cardiovascular system. B1 cells, which arise predominantly during fetal development, are found in body cavities, such as the perivascular adipose tissue (PVAT) and peritoneum. Guided by CXCL13 and CCR6, they migrate to sites, where they produce IgM and IgG3, contributing to immune regulation and pathogen defense. In contrast, B2 cells-central players in adaptive immunity-originate in the bone marrow and mature in secondary lymphoid organs. Within this subset, marginal-zone (MZ) B cells provide rapid, low-affinity IgM responses to blood-borne antigens, while follicular (FO) B cells mediate high-affinity, T-cell-dependent antibody production. For all of the latter chemokine-guided migration is essential for B-cell function, from immune surveillance to antibody secretion. Receptors such as CXCR4, CXCR5, and ACKR3 not only direct B-cell trafficking but also influence their phenotype in cardiovascular disease. Understanding how these chemokine-receptor interactions shape B-cell-mediated immunity in CVD may allow for developing targeted therapies for atherosclerosis, myocardial infarction, and stroke.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"11 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117131","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 CNP analogue vosoritide mediates PDE2-sensitive anti-arrhythmogenic effects in mouse hearts with STZ-induced type 1 diabetes.","authors":"Rebecca Firneburg,Katharina Tergau,Eleder Cachorro,Mario Schubert,Anindita Dhara,Xiaojing Luo,Erik Klapproth,Kaomei Guan,Ali El-Armouche,Susanne Kämmerer","doi":"10.1007/s00395-025-01141-w","DOIUrl":"https://doi.org/10.1007/s00395-025-01141-w","url":null,"abstract":"Diabetes mellitus induces adverse structural, electrophysiological and autonomic remodelling increasing the risk for life-threatening arrhythmias, particularly after acute myocardial infarction. Natriuretic peptides (NPs) show increasing evidence of antagonising arrhythmia. Our previous study demonstrated that C-type NP (CNP) reduces arrhythmia after ischaemia-reperfusion injury (I/R) via the cGMP-dependent phosphodiesterase 2 (PDE2) in healthy mice. However, the clinical use of CNP is challenging due to its short plasma half-life. To address this, we investigated whether the more stable CNP analogue vosoritide (VO) reduces arrhythmia at cellular and organ levels in mice with STZ-induced type 1 diabetes (50 µg/g, i.p. for 5 days). After 5 weeks, STZ treatment led to elevated blood glucose and HbA1c levels, impaired cardiac function, and an increased incidence of arrhythmia after I/R in ex vivo perfused hearts. Cardiac PDE2 expression was similarly increased in diabetic mice and diabetic patients with dilated cardiomyopathy. Notably, cGMP-mediated PDE2 activation via VO clearly reduced arrhythmia generation after I/R in ex vivo perfused hearts from diabetic mice (Cohen's d = 2.3). In cardiomyocytes, VO significantly decreased pro-arrhythmic signals upon β-adrenergic stress, such as spontaneous Ca2+ waves and sparks (Cohen's d = 1.0) or L-type Ca2+ current amplitudes (Cohen's d = 1.6). Specific PDE2 inhibition with BAY 60-7550 or genetic cardiomyocyte-specific PDE2 deletion prevented the anti-arrhythmic VO effects. Importantly, VO did not affect the QT interval, action potential duration, or contraction of cardiomyocytes from diabetic mice. Thus, the modified natriuretic peptide VO may serve as a promising therapeutic option to prevent lethal arrhythmias in susceptible diabetic patients.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"71 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077725","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":"Downregulation of TCF19 and ATAD2 causes endothelial cell cycle arrest at the transition from cardiac hypertrophy to heart failure.","authors":"Elias Erny,Christoph Koentges,Debanjan Mukherjee,Luisa Wirth,Christos Kamaras,Franziska Zell,Madelon Hossfeld,Olaf Groß,Achim Lother","doi":"10.1007/s00395-025-01139-4","DOIUrl":"https://doi.org/10.1007/s00395-025-01139-4","url":null,"abstract":"Cardiac hypertrophy is a key mechanism that allows the heart to adapt to increased load, but in the long term is associated with a higher risk for heart failure, arrhythmia, and death. During hypertrophic growth, cardiac myocytes signal to endothelial cells via vascular endothelial growth factor (VEGF) to promote angiogenesis and maintain myocardial oxygen supply. Insufficient angiogenesis leads to a decline in capillary density and drives the progression from compensated cardiac hypertrophy to heart failure. Here, we studied the time course of endothelial cell gene expression during heart failure development and identified transcriptional regulators of cell proliferation and angiogenesis. We applied transverse aortic constriction (TAC) in mice and isolated cardiac endothelial cells for RNA sequencing after 6 h and 1, 3, 7, or 28 days to create an inventory of gene expression during the course of cardiac hypertrophy and failure. Echocardiography revealed that decompensated heart failure occurred between days 7 and 28 after TAC. At the same time, we observed a switch in endothelial cell gene expression with an upregulation of proliferation markers in the hypertrophy state but downregulation in decompensated heart failure. Of note, endothelial cell cycle arrest occurred despite strong VEGF signaling from cardiac myocytes, indicating VEGF resistance. To investigate how endothelial cell proliferation is transcriptionally regulated, we performed a weighted gene co-expression network analysis and identified a module of 180 cell cycle-related genes. We predicted transcription factor 19 (TCF19), ATPase family AAA domain containing 2 (ATAD2), and transcription factor Dp-1 (TFDP1) to be central regulators of this gene module. Knockdown of TCF19 and ATAD2 by siRNA in HUVECs led to a downregulation of the marker of proliferation MKI67 and repressed cell proliferation, tube formation, and cell migration, confirming their regulatory function. In heart tissue biopsies from patients with aortic stenosis, TCF19 and ATAD2 abundance were positively correlated with endothelial cell proliferation. TCF19 or ATAD2 control the expression of a gene network involved in endothelial cell proliferation and angiogenesis. Downregulation of TCF19 and ATAD2 is associated with endothelial cell cycle arrest and an impaired angiogenic response to VEGF signaling that may promote the transition from compensated cardiac hypertrophy to heart failure.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"30 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077726","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":"NLRP3 mediates lipid-driven macrophage proliferation in established atherosclerosis.","authors":"Carmen Härdtner,Felix Remmersmann,Carolin Ehlert,Christina Zehender,Tamara Antonela Vico,Bianca Dufner,Alexander von Ehr,Julia Hinterdobler,Xiaowei Li,Guido Pisani,Filip K Swirski,Constantin von Zur Mühlen,Dennis Wolf,Martin Czerny,Olaf Groß,Hendrik B Sager,Dirk Westermann,Ingo Hilgendorf","doi":"10.1007/s00395-025-01137-6","DOIUrl":"https://doi.org/10.1007/s00395-025-01137-6","url":null,"abstract":"An increased number of macrophages in the atherosclerotic plaque is associated with plaque instability and plaque progression. Lowering systemic cholesterol levels suppresses local macrophage proliferation and leads to plaque regression. However, the pathways regulating macrophage proliferation remain poorly understood. We investigated the cellular processes that underlie lipid-triggered local macrophage proliferation in the atherosclerotic plaque in transgenic mice and in human plaque tissue samples. Macrophages from mice with genetic deficiencies in scavenger receptors Cd36-/- and Msr1-/- showed reduced lipid uptake, lower intracellular lipid content, and lower proliferation compared to wild type macrophages. Double knockouts for the cholesterol exporters Abca1 and Abcg1 (MAC-ABC-DKO) showed increased rates of macrophage proliferation and apoptosis. In Cd36-/-, Msr1-/-, and MAC-ABC-DKO mixed bone marrow chimeras, no differences in chimerism were observed in blood or aorta after 4 weeks on a high-cholesterol diet. After 12 weeks of atherogenic diet, wild type macrophages predominated in the aorta since they proliferated more than neighboring Cd36-/- or Msr1-/- macrophages, and were less apoptotic than ABC-DKO macrophages, respectively. Knockout of NLRP3, but not ASC, Caspase 1 or IL-1 receptor, limited macrophage proliferation; indicating an NLRP3-dependent, but inflammasome-independent, effect. Inhibition of NLRP3 by MCC950 in human carotid artery plaque tissue cultures resulted in the suppression of intra-plaque macrophage proliferation and IL-1β release consistent with murine in vivo data. We identified a novel role for NLRP3 in driving macrophage proliferation in atherosclerotic plaques. NLRP3 inhibition may represent an ideal therapeutic target in atherosclerosis by combining anti-inflammasome and anti-proliferative effects in macrophages.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"66 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068349","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":"Renal denervation attenuates cardiac dysfunction in HFpEF by inhibiting the ATP-P2X7-NLRP3 inflammasome axis.","authors":"Zhuqing Li,Xiaoqiang Sun,Yanxin Wang,Feng Zhang,Li Wang,Chunbo Ai,Xu Zhang,Xuemei Yin,Chunlei Liu,Chao Li,Chengzhi Lu","doi":"10.1007/s00395-025-01138-5","DOIUrl":"https://doi.org/10.1007/s00395-025-01138-5","url":null,"abstract":"Heart failure with preserved ejection fraction (HFpEF) arises from intersecting comorbidities involving inflammation, metabolic stress, and sympathetic nervous system (SNS) activation. To mirror this complexity, we established a clinically oriented 3-hit mouse model combining advanced age, a high-fat diet, and chronic NOS inhibition with NG-Nitro-L-arginine methyl ester (L-NAME). We tested whether renal denervation (RDN) mitigates HFpEF by blunting SNS outflow and the ATP-P2X7-NLRP3 inflammasome axis, and in parallel probed the contribution of this pathway using pharmacologic and cellular approaches. 3-hit mice developed preserved ejection fraction with diastolic dysfunction, cardiomyocyte hypertrophy, interstitial fibrosis, impaired exercise capacity, and elevated inflammatory cytokines, accompanied by increased myocardial ATP, activation of P2X7/NLRP3 signaling, oxidative stress, and pyroptosis.RDN lowered systemic and myocardial norepinephrine, suppressed P2X7-NLRP3 inflammasome activation, reduced fibrosis and cardiomyocyte cross-sectional area, improved E/e' and exercise capacity, and reduced oxidative stress and myocardial injury. In pharmacological intervention experiments, selective blockade with the P2X7 antagonist A438079 or the NLRP3 inhibitor MCC950 improved diastolic function and exercise capacity and attenuated myocardial fibrosis and cardiomyocyte hypertrophy. Complementary mechanistic studies in cardiomyocytes (H9c2 and primary neonatal rat cardiomyocytes) showed that ATP induced mitochondrial ROS accumulation, inflammasome activation, cytokine release, and cell injury, which were partially reversed by P2X7 knockdown or pharmacological antagonism. Together, these data validate a multi-hit HFpEF model and implicate an SNS-driven ATP-P2X7-NLRP3 axis as a potential therapeutic target. Both RDN and selective pathway inhibition improved diastolic function and attenuated ventricular remodeling, and inform future therapeutic strategies for HFpEF characterized by heightened sympathetic tone.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"38 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071763","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":"Cardiac sodium-glucose co-transporter 1 (SGLT1) contributes to heart failure in a mouse model of diabetic cardiomyopathy.","authors":"Zhao Li,Sydney Freiberg,Meredith L Music,Lina Gu,Sarah Nacos,Joseph P Phillips,Adil Hassan,Kamel Shibbani,Sanah S Munir,Vooha K Kumar,Luke Halligan,Mia E Michel,Benjamin F London,Ngan Bui,Michael Cicha,Valerie Buffard,E Dale Abel,Ferhaan Ahmad","doi":"10.1007/s00395-025-01136-7","DOIUrl":"https://doi.org/10.1007/s00395-025-01136-7","url":null,"abstract":"Diabetes mellitus can lead to a cardiomyopathy independent of other risk factors such as coronary artery disease and hypertension, in up to 75% of patients. The prevalence of diabetic cardiomyopathy in the population is 1.1%. We previously showed that SGLT1 is expressed in cardiomyocytes and is further upregulated in diabetic cardiomyopathy and other forms of heart failure. In this study, we sought to determine the mechanisms by which cardiac SGLT1 contributes to the pathophysiology of heart failure in diabetes, obesity, and insulin resistance. We determined whether transgenic mice with cardiomyocyte-specific knockdown of SGLT1 (TGSGLT1-DOWN) had attenuation of cardiomyopathy after induction of obesity and insulin resistance by exposure to a high fat diet (HFD) from ages 8-28 weeks. TGSGLT1-DOWN mice and wildtype (WT) littermates exhibited similar increases in body weight and blood glucose after exposure to HFD. Nevertheless, TGSGLT1-DOWN mice exhibited attenuation of cardiomyopathy, manifested by less hypertrophy, systolic and diastolic dysfunction, fibrosis, nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2) activation, and reactive oxygen species (ROS) production. In vivo hyperinsulinemia and in vitro exposure of cardiomyocytes to high glucose or insulin led to an increase in SGLT1 expression by increasing binding of the transcription factors HNF-1 and Sp1 to the SGLT1 gene (Slc5a1), and the transcript stabilizer HuR to SGLT1 mRNA. SGLT1 may contribute to cardiac injury in obesity and insulin resistance by stimulating ROS through its interaction with EGFR. SGLT1 may represent a therapeutic target for inhibition to prevent or to reverse diabetic cardiomyopathy.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"15 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032118","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":"Calcific aortic valve disease augments vesicular microRNA-145-5p to regulate the calcification of valvular interstitial cells via cellular crosstalk.","authors":"P R Goody, D Christmann, D Goody, S Hildebrand, H Billig, D Nehl, R Chennupati, M Gladka, K Wilhelm-Jüngling, S Uchida, S Iris-Bibli, J B Moore, N Hamdani, F Paneni, S S Pullamsetti, S Zimmer, F Jansen, F Bakhtiary, E Aikawa, A Pfeifer, G Nickenig, M R Hosen","doi":"10.1007/s00395-025-01133-w","DOIUrl":"https://doi.org/10.1007/s00395-025-01133-w","url":null,"abstract":"<p><p>Calcific aortic valve disease (CAVD) is one of the leading causes of cardiovascular death in the elderly population worldwide. MicroRNAs (miRNAs) are highly dysregulated in patients with CAVD undergoing surgical aortic valve replacement (SAVR). However, the miRNA-dependent mechanisms regulating inflammation and calcification or miRNA-mediated cell-cell crosstalk during the pathogenesis of CAVD remain poorly understood. Here, we investigated the role of extracellular vesicle (EV)-associated miR-145-5p, which we showed to be strongly upregulated in CAVD in mice and humans during valve calcification. Human TaqMan miRNA arrays identified dysregulated miRNAs in CAVD tissue explants from patients compared to non-calcified (patients with aortic insufficiency) heart valve tissue explants from patients undergoing SAVR. Echocardiographic parameters were measured in conjunction with the quantification of dysregulated miRNAs in a murine CAVD model. In vitro calcification experiments were performed to investigate the effects of EV-miR-145-5p on calcification and crosstalk in heart valve cells. Integrated OMICS analyses were performed to analyze molecular miRNA signatures and their effects on signaling pathways-associated with CAVD. RNA sequencing, high-throughput transcription factor (TF) activity assays, and osteogenesis arrays revealed that a number of genes, miRNAs, TFs are critical for calcification and apoptosis involved in the pathogenesis of CAVD. Among several miRNAs dysregulated in valve explants from CAVD patients, miR-145-5p was the most highly sex-independently upregulated miRNA (AUC, 0.780, p value, 0.01) in patient plasma. Large EV population (170-800 nm) isolated from aortic valve tissues explanted from patients with CAVS (calcific aortic valve stenosis) after SAVR demonstrated a significantly higher level of miR-145-5p expression in comparison to control (vesicle-free plasma). MiRNA arrays utilizing with aortic stenosis samples from patients and mice showed that the expression of miR-145-5p is significantly upregulated and positively correlated with cardiac function based on echocardiography. In vitro experiments confirmed that miR-145-5p is encapsulated in EVs and transported into interstitial cells of the aortic valve. The results of integrated OMICs show that miR-145-5p is related to markers of inflammation, calcification, and apoptosis. In vitro calcification experiments demonstrated that miR-145-5p regulates the ALPL gene, a hallmark of calcification in vascular and heart valve cells. Mechanistically, EV-mediated shuttling of miR-145-5p suppressed the expression of ZEB2, a negative regulator of the ALPL gene, by binding to its 3' untranslated region to inhibit its translation, thereby diminishing the calcification of valvular interstitial cells. Elevated levels of pro-calcific and pro-apoptotic EV-associated miR-145-5p contribute to the progression of CAVD via the ZEB2-ALPL axis, which could potentially be therapeutically targeted t","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940654","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":"Alpha-ketoglutarate protects against myocardial infarction via FTO-mediated anti-inflammatory macrophage activation.","authors":"Zhijun Lin,Huan He,Pinliang Chen,Xin Dong,Jialin Jiang,Weiwei Huang,Zigang Pan,Zhuoji Guan,Lu Lu,Huan Li,Yusheng Huang,Zhong Wang,Tong Luo,Lingjun Wang,Zixin Chen","doi":"10.1007/s00395-025-01135-8","DOIUrl":"https://doi.org/10.1007/s00395-025-01135-8","url":null,"abstract":"Ischemic heart disease lacks optimal therapies targeting post-infarction inflammation and remodeling. The role of TCA cycle metabolites in modulating macrophage-driven cardiac inflammation remains unclear. This study hypothesized that AKG supplementation attenuates cardiac dysfunction by regulating macrophage activation via TCA cycle replenishment and FTO-dependent epigenetic mechanisms. Myocardial infarction was induced in male C57BL/6 mice and macrophage-specific FTO knockout mice via left anterior descending artery ligation. Mice received AKG supplementation. Techniques included echocardiography, histopathology, flow cytometry (quantifying Ly6C+ macrophages), m6A-RIP-qPCR (assessing Stat3 mRNA methylation), Western blotting (JAK1/STAT3 pathway), Seahorse metabolic analysis (BMDMs), and in vitro BMDM cultures. Data are mean ± SD; statistical significance (p < 0.05) assessed by t-test/ANOVA. AKG restored TCA cycle flux and significantly reduced infarct size (p < 0.01). It attenuated pro-inflammatory Ly6C+ macrophage infiltration (p < 0.05) versus controls. AKG required macrophage FTO expression, increasing STAT3 nuclear translocation (p < 0.05) via FTO-mediated m6A demethylation of Stat3 mRNA (p < 0.01). This activated JAK1/STAT3 signaling, driving anti-inflammatory polarization and metabolic reprogramming (p < 0.05). AKG supplementation attenuates post-infarction cardiac dysfunction primarily through FTO-mediated m6A demethylation of Stat3 in macrophages, activating JAK1/STAT3 signaling to promote anti-inflammatory polarization and metabolic reprogramming. This defines a novel metabolite-epigenetic pathway (AKG-FTO-m6A-STAT3) for immunomodulation in ischemic injury, highlighting TCA cycle replenishment as a therapeutic strategy.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"27 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857688","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 influence of acute and chronic coronary syndrome on the gut microbiome and downstream microbiome-derived metabolites-Microbiome in acute myocardial infarction-MIAMI-Trial.","authors":"Daniel Messiha, Erik Lange, Annika Tratnik, Astrid M Westendorf, Miriam Rinke, Stine Lenz, Ulrike B Hendgen-Cotta, Jan Buer, Tienush Rassaf, Christos Rammos","doi":"10.1007/s00395-025-01134-9","DOIUrl":"https://doi.org/10.1007/s00395-025-01134-9","url":null,"abstract":"<p><p>Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the industrialized world. The gut microbiome influences CVD, through atherogenic metabolites like trimethylamine N-oxide (TMAO) or protective effects through short-chain fatty acids (SCFA) production. The specific alterations in the gut microbiome and downstream metabolites in acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) remain unclear. We enrolled ACS patients within 24 h of clinical presentation with a follow-up of 28 days, using CCS patients as controls. Gut microbiome composition, downstream metabolites, and cardiovascular function were assessed at both baseline and follow-up. Microbiome-derived metabolites were analyzed and gut microbiome samples were characterized by 16S rRNA gene analysis. We enrolled 40 patients, with 20 patients each in the ACS and CCS group. Alpha diversity of the microbiome did not differ throughout the follow-up. After ACS gut microbiome composition changed during the follow-up period with increased levels of Butyricicoccus and Butyricoccaceae, a pattern not observed in the CCS cohort. Downstream analysis of microbiome-derived metabolites SCFA revealed increased serum levels of butanoic acid, while TMAO levels remained unchanged. This small prospective observational non-randomized study, suggests that ACS may trigger an enrichment of butanoic acid-producing bacteria in the gut microbiome, accompanied by an increase in serum butanoic acid levels over 28 days. No significant changes in TMAO were observed. These insights could help develop approaches to reduce the burden of CVD. As a small pilot study, these findings require validation in larger ACS cohorts. Trial registration NCT, NCT05456802, Registered 30 June 2022, https://clinicaltrials.gov/study/NCT05122689.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844293","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":"Sex differences in a murine model of infective endocarditis.","authors":"Benedikt Bartsch,Raúl Nicolas Jamin,Axel Schott,Muntadher Al Zaidi,Nikola Lübbering,Hannah Billig,Christian Kurts,Georg Nickenig,Marijo Parcina,Sebastian Zimmer,Christina Katharina Weisheit","doi":"10.1007/s00395-025-01127-8","DOIUrl":"https://doi.org/10.1007/s00395-025-01127-8","url":null,"abstract":"Infective endocarditis (IE) is a highly lethal disease with a notable male predominance, yet the biological basis for this sex disparity remains unclear. We established a murine IE model in C57BL6 mice in which aortic valve injury was induced via wire-injury and followed by intravenous injection of Staphylococcus aureus. Infection was confirmed by blood and valve cultures, and cardiac function was evaluated by echocardiography. Systemic cytokine levels were measured, and immune cell infiltration in valve tissue was assessed by flow cytometry and immunofluorescence. In the murine model, IE was induced in 77/85 animals. Male mice exhibited significantly higher bacterial loads in blood and valves, greater valve cusp enlargement, increased ventricular volumes, and more frequent aortic regurgitation. Both sexes showed strong neutrophilic responses, but males had markedly elevated systemic IL-1α, IL-1β, IL-6, and TNF-α levels. Females demonstrated earlier and more robust recruitment of CD68⁺ and CD206⁺ macrophages, as well as Ly6G⁺ neutrophils, to the injured valve, correlating with reduced bacterial vegetations. This murine model mirrors the clinical sex disparity in IE: males develop more severe disease and systemic inflammation, while females benefit from a rapid, localized immune response. These findings provide a platform for dissecting molecular drivers of sex-specific susceptibility in IE.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"113 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791939","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}