Basic Research in Cardiology最新文献

{"title":"Short-chain fatty acids promote post-myocardial infarction cardiac repair via FFAR2-dependent suppression of osteoclast-like macrophage differentiation.","authors":"Qun Zhang, Xue Jiang, Lu Liu, Yu-Meng Jia, Pan-Pan Yu, Jie Zhang, Xin-Ying Guo, Jing-Jing Wang, Cai-Xia Guo, Lei Wang","doi":"10.1007/s00395-026-01212-6","DOIUrl":"https://doi.org/10.1007/s00395-026-01212-6","url":null,"abstract":"<p><p>Adverse cardiac remodeling leads to the development of heart failure following myocardial infarction (MI), yet the immunometabolic signals governing early infarct repair remain poorly understood. Short-chain fatty acids (SCFAs) are important immunometabolic regulators, but their relevance and mechanistic contribution to post-MI repair remain unclear. Here, we integrated clinical observations with genetic and pharmacological intervention studies to investigate the role of the SCFAs-free fatty acid receptor 2 (FFAR2) axis in post-MI repair. Circulating SCFAs levels were markedly decreased in patients with MI, and associated with more complex coronary lesions and a higher risk of major adverse cardiovascular events. In murine MI, SCFAs supplementation reduced infarct expansion, cardiomyocyte death, and cardiac rupture, and improved left-ventricular function. These benefits were lost in global and myeloid-specific Ffar2-deficient mice, demonstrating an essential role for myeloid FFAR2 in SCFA-mediated cardioprotection. Mechanistically, SCFAs activated FFAR2-G_αi signaling in macrophages to suppress RANKL-RANK-driven osteoclast-like macrophage differentiation. thereby enhancing early fibrotic stabilization, reducing cardiomyocyte apoptosis, and improving infarct healing. Pharmacological blockade of osteoclast-like macrophage activation partially rescued impaired healing and cardiac dysfunction in myeloid-specific Ffar2-deficient mice after MI. These findings identify circulating SCFAs as clinically relevant biomarkers associated with coronary lesion complexity and adverse clinical outcomes after MI, and establish the SCFAs-FFAR2 axis as an immune-metabolic pathway that orchestrates macrophage fate and infarct healing. Targeting SCFAs-FFAR2 signaling may represent a therapeutic strategy to limit adverse post-MI remodeling and prevent heart failure.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015589","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":"Enhanced myelopoiesis and myeloid TREM1 upregulation link obesity with adverse outcomes after myocardial infarction","authors":"Nadine Gladow,Ines Klohr,Xin Ding,Panagiota Arampatzi,Mugdha Srivastava,Jan Traub,Stefan Frantz,Gustavo Ramos,Ulrich Hofmann","doi":"10.1007/s00395-026-01207-3","DOIUrl":"https://doi.org/10.1007/s00395-026-01207-3","url":null,"abstract":"Abstract Obesity induces a systemic low-grade inflammatory activation of the innate immune system potentially impairing early outcomes after myocardial infarction (MI). This study aims to analyse the impact of diet-induced obesity on myelopoiesis, myocardial inflammation, left ventricular function and survival in an experimental mouse model of MI. Male and female C57BL6/J mice were fed either a high-fat (60 kJ %) or a low-fat (10 kJ %) diet. Experimental myocardial infarction was induced after 16 weeks of feeding. Left ventricular function was studied by echocardiography. Hematopoietic progenitors and peripheral leukocytes were analysed by flow cytometry. Male obese mice exhibited notably higher body weight, significantly increased myelopoiesis in the spleen and higher leukocyte counts in peripheral blood than their female counterparts. Survival over 56 days after myocardial infarction was significantly impaired in obese compared to lean mice (58% vs. 87%). In obese mice, we found significantly elevated myocardial infarction-induced myelopoiesis in the spleen and higher granulocyte, monocyte and pro-inflammatory macrophage numbers in the myocardium. Moreover, RNA-sequencing and immunohistology revealed enhanced triggering receptor expressed on myeloid cells 1 (TREM1) expression in obese compared to lean mice on day 5 after myocardial infarction. Blockade of TREM1 led to significantly better preservation of systolic function in obese mice. After myocardial infarction, obese mice of both sexes showed enhanced myelopoiesis and impaired survival compared to lean mice. TREM1 blockade might be a promising therapeutic strategy for preserving systolic function in obese patients with myocardial infarction.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"8 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148933643","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":"Delayed intracardiac remote ischemic preconditioning reduces infarct size in remote myocardium of pigs.","authors":"Denise Traxler, Dominika Lukovic, Andreas Spannbauer, Ena Hasimbegovic, Nina Kastner, Martin Riesenhuber, Katrin Zlabinger, Lisa Auer, Noemi Pavo, Gerd Heusch, Mariann Gyöngyösi","doi":"10.1007/s00395-026-01208-2","DOIUrl":"https://doi.org/10.1007/s00395-026-01208-2","url":null,"abstract":"<p><p>Cardioprotection induced by repetitive ischemia/reperfusion (I/R) is not confined to the ischemic region but may extend to distant myocardial territories, a phenomenon termed intracardiac remote ischemic preconditioning (icRIPC). The present study aimed to evaluate the delayed effects of icRIPC on infarct size (IS), left ventricular (LV) function (LVF), and myocardial gene and protein expression. icRIPC was induced in 13 pigs by 3 cycles of 10 min ischemia/10 min reperfusion of the left anterior descending coronary artery (LAD) (conditioning) territory, followed 24 h later by reperfused acute myocardial infarction (AMI) of the left circumflex artery (LCx) (infarcted) territory, induced by 90-min percutaneous balloon occlusion of the mid LCx followed by reperfusion (group icRIPC-AMI). Thirteen additional pigs underwent a sham icRIPC procedure followed by reperfused LCx AMI 24 h later and served as controls (group AMI). Five pigs from each group were euthanized at 3 days, and myocardial expression of nine selected genes was quantified by RT-qPCR in the distal LAD and LCx territories. Protein expression of the two significantly upregulated genes was assessed by Western blot. The remaining eight pigs in each group were followed for 1 month. At 3 days after reperfused AMI, superoxide dismutase-2 (SOD2) protein expression was increased in the infarcted LCx territory of the icRIPC-AMI group, whereas inducible nitric oxide synthase (iNOS/NOS2) protein expression was increased in the distal LAD territory. At 1 month, IS was lower in the icRIPC-AMI than in the AMI group (8.4±3.7% vs. 14.1±1.8% of LV mass, p=0.003), whereas global LVF was marginally improved. However, segmental mean contraction velocity of the infarcted lateral wall was higher in the icRIPC-AMI than in the AMI group (14.8±1.6 vs. 13.3±0.9 mm/s, p=0.026). These findings provide potentially mechanistic evidence for delayed icRIPC, characterized by reduced IS, improved regional myocardial function, and territory-specific changes in cardioprotective protein expression, and may represent an experimental correlate of the clinical phenomenon of pre-infarction angina.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863203","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 in experimental autoimmune myocarditis: association with cardiac function and changes in calcium and MAPK/ERK signaling.","authors":"Ya-Wen Hsiao, Wei-Lun Lin, Yu-Hui Chou, Shih-Ann Chen, Li-Wei Lo","doi":"10.1007/s00395-026-01183-8","DOIUrl":"10.1007/s00395-026-01183-8","url":null,"abstract":"<p><p>Renal denervation (RDN) has emerged as a potential therapeutic strategy to modulate autonomic imbalance and attenuate inflammation in cardiovascular disease. However, the mechanisms underlying its cardioprotective effects remain incompletely understood. In this study, we evaluated the functional and molecular effects of RDN in a rabbit model of experimental autoimmune myocarditis (EAM). A total of twenty-four male New Zealand white rabbits were randomly assigned to four groups: control, EAM, EAM with RDN for 4 weeks (EAM-RDN4W), and EAM with RDN for 6 weeks (EAM-RDN6W). Echocardiographic assessment demonstrated that EAM induced marked systolic dysfunction, as reflected by a reduction in left ventricular ejection fraction (LVEF) (approximately 65% in CTRL vs. 36% in EAM), whereas RDN was associated with partial preservation of cardiac performance, with recovery of LVEF to ~ 52% at 6 weeks after RDN. Histological analysis and TUNEL staining showed that RDN was associated with attenuation of myocardial inflammatory infiltration and cardiomyocyte apoptosis. RDN also reduced sympathetic activation, as evidenced by reduced ChAT-positive area in cardiac tissue and decreased circulating catecholamine levels. At the molecular level, RDN was associated with a shift toward improved calcium-handling balance, characterized by downregulation of Cav1.2, NCX, and RyR and upregulation of SERCA2a and phosphorylated phospholamban (p-PLB). Furthermore, RDN was associated with reduced activation of the MAPK/ERK pathway, as evidenced by decreased phosphorylation of Raf, MEK, ERK, and CREB. Collectively, these findings indicate that RDN is associated with improved cardiac function in EAM and with mitigation of inflammation-related myocardial injury, in parallel with coordinated changes in neurohumoral activity, calcium signaling, and MAPK/ERK pathway activation.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"739-754"},"PeriodicalIF":9.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004331","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":"Coronary endothelial cells undergo venous-enriched disrupted maturation following myocardial infarction.","authors":"Kaitlyn Ford, Hosanna Abbay, Amy S Leonardson, Jennifer M Franks, Nicholas W Chavkin","doi":"10.1007/s00395-026-01190-9","DOIUrl":"10.1007/s00395-026-01190-9","url":null,"abstract":"<p><p>The coronary microvascular plexus responds to cardiac ischemia through angiogenic neovascularization in the ischemic and border zones to sustain the demand for oxygen and nutrients. Although new blood vessels form, the process of endothelial maturation and extent to which the post-injured microvascular plexus resembles the pre-injured state is unclear. Developmental processes suggest that neovascular endothelial cells must specify toward arterial or venous fates to generate a continuum of heterogenous identities across the microvascular plexus. Therefore, we investigated whether coronary endothelial cells undergo similar arterial-venous specification after ischemia and return to a pre-injured maturation state. Cardiac single-cell RNA sequencing datasets from a murine myocardial infarction model isolated over time post-injury were analyzed for endothelial cell fate dynamics through gene expression and cell trajectory. We found that murine coronary endothelial cells undergo arterial-venous specification at later time points following ischemia-induced angiogenesis. However, post-injured endothelial cells express a reduction of genes associated with arterial-venous identity and blood vessel development with early dysregulation of signaling pathways required for arterial-venous specification. These transcriptional changes are associated with disrupted heterogeneity of the post-injured microvascular plexus and a shift toward venous fate. Endothelial cells in cardiac tissue of ischemic cardiomyopathy patients also mirror the disrupted gene patterns, signaling pathways, and venous-shifted heterogeneity. Using primary human coronary microvascular endothelial cells, we identified that arterial identity is promoted by TGF signaling and inhibited by WNT signaling. Finally, spatial sequencing datasets from human ischemic cardiomyopathy of different injured cardiac zones identified that the venous-shifted maturation state is enriched in the border zone and associates with POSTN expression. These results suggest that the post-injured coronary microvascular plexus is driven to a venous-shifted fate in the border zone, revealing disrupted arterial-venous heterogeneity as a potential hallmark of ischemic heart failure.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"629-651"},"PeriodicalIF":9.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aortic baroreceptor afferents as sensors for systemic inflammation.","authors":"Fernanda Brognara, Jaci Airton Castania, Mirele Resende Machado, José Teles de Oliveira Neto, Helio Cesar Salgado, Rita de Cassia Tostes, Daniel Penteado Martins Dias, Julian Francis Richmond Paton, Evelin Capellari Cárnio","doi":"10.1007/s00395-026-01188-3","DOIUrl":"10.1007/s00395-026-01188-3","url":null,"abstract":"<p><p>Neuroimmune communication is essential for regulating inflammation and maintaining cardiovascular homeostasis, but the role of sensory pathways in this process is poorly understood. Arterial baroreceptors are typically defined as mechanoreceptors essential for arterial pressure homeostasis and have been associated with modulation of the immune response. However, their role in sensing systemic inflammation remains unknown. Here, we establish the molecular profile of the rat aortic depressor nerve (ADN) as an immune-competent tissue and investigate its response to lipopolysaccharide (LPS)-induced endotoxemia. Using analysis of gene expression, total protein quantification, and immunofluorescence assay, we demonstrate that the ADN, from male Sprague-Dawley rats (7-8 weeks old), constitutively expresses key components for innate immune signalling, including Toll-like receptor 4 (TLR4), MyD88, and phosphorylated NF-κB, indicating a state of constant immunological vigilance. LPS administration induced an inflammatory response within the ADN, upregulating gene expression of NF-κB, interleukin-6, and type I interleukin 1 receptor, and it also increased the ADN electrical activity. Notably, the increase in nerve firing occurred while the animals were experiencing systemic hypotension and also during the diastolic phase, indicating that this response is not from the mechanosensory reflex. Furthermore, we characterized the progression of this immune response in the nodose ganglion and aortic arch, identifying a coordinated neuroimmune sensory axis. These findings reposition arterial baroreceptors from purely mechanoreceptors to integrative immunosensors that actively detect and respond to systemic inflammation. This novel neuroimmune circuit represents a critical link between inflammation and cardiovascular system, offering a novel therapeutic target for treating cardiovascular and inflammatory conditions.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"755-773"},"PeriodicalIF":9.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148238569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toll-like receptor 7 constrains efferocytosis in myocardial injury.","authors":"Yanqiu Lai, Suet Yen Chong, Vaarsha Nair, Wenhui Cui, Linjie Li, Shuting Liu, Xin Zhao, Liqiang Yang, Xiao Hou, Olga Zharkova, Baptiste Janela, Xin Zhou, Mark Y Chan, A Mark Richards, Qing Yang, Jiong-Wei Wang","doi":"10.1007/s00395-026-01185-6","DOIUrl":"10.1007/s00395-026-01185-6","url":null,"abstract":"<p><p>Toll-like receptor 7 (TLR7) is an endosomal sensor of single-stranded RNA that is highly expressed in macrophages and contributes to post-infarct inflammation. Whether TLR7 also restrains macrophage reparative function, particularly efferocytosis and clearance of inflammatory debris, remain unclear. Using a murine model of myocardial ischemia-reperfusion (I/R) injury, we showed that TLR7 deficiency mitigated inflammation, reduced infarct size and alleviated adverse ventricular remodeling. Beyond its anti-inflammatory effects, TLR7 deficiency reprogrammed macrophages toward a reparative phenotype, characterized by decreased pro-inflammatory cytokine production and increased expression of anti-inflammatory mediators, including IL-10 and TGF-β, consistent with M2-like polarization. Single-cell RNA sequencing revealed a subset-specific mechanism in which TLR7 deficiency suppressed inflammatory signaling in M1 macrophages while enhancing efferocytosis-related pathways in M2 macrophages. This was accompanied by upregulation of key phagocytic receptors and machinery, including CD36, LRP1, MerTK, AXL and Rac1, and functionally translated into enhanced efferocytic capacity and reduced apoptotic burden. Notably, TLR7 deficiency also promoted macrophage-mediated clearance of neutrophil extracellular traps (NETs) without affecting NETosis, identifying a previously unrecognized role for TLR7 in regulating NET resolution. Consistent with these findings, NET formation was observed following myocardial injury in both murine I/R models and patients undergoing percutaneous coronary intervention.In conclusion, our data identify TLR7 as a macrophage-intrinsic checkpoint that limits efferocytosis and NET disposal, thereby impairing inflammation resolution after myocardial injury. Targeting TLR7 may therefore represent a therapeutic strategy to suppress excessive inflammation while restoring pro-resolving macrophage functions and improving cardiac repair.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"689-710"},"PeriodicalIF":9.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947960","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":"Empagliflozin restores cardiac function in obese-diabetic HFpEF mice but further alters gene expression.","authors":"Juliana Mira Hernandez, Logan R J Bailey, Victoria R Salemme, Christopher Y Ko, Erin Y Shen, Megan Ngim, Duong T Hoang, Melissa Corea, Julie Bossuyt, Jennifer M Davis, Donald M Bers, Bence Hegyi","doi":"10.1007/s00395-026-01184-7","DOIUrl":"10.1007/s00395-026-01184-7","url":null,"abstract":"<p><p>Effective treatments for heart failure with preserved ejection fraction (HFpEF) are limited. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, provides cardiovascular benefits for patients with HFpEF. SGLT2 expression is virtually absent in cardiomyocytes, hence the exact protective mechanism of empagliflozin is unclear. We aimed to study the effect of in vivo empagliflozin treatment on excitation-contraction coupling (ECC), electrophysiology, and gene transcription in a translational two-hit HFpEF mouse model that combines the obese-diabetic leptin receptor-deficient db/db mice with chronic aldosterone infusion (db/db + Aldo). We performed morphometry, echocardiography, cardiomyocyte electrophysiology, intracellular Ca²⁺ imaging, and whole-heart RNA-sequencing in empagliflozin-treated db/db + Aldo and vehicle control mice. In db/db + Aldo mice, empagliflozin (in vivo, 4 weeks) reduced the elevated plasma blood glucose (13 ± 5 mmol/L versus 23 ± 8 mmol/L) and BNP levels, prevented pulmonary congestion, and ameliorated diastolic dysfunction. However, empagliflozin did not reduce cardiac hypertrophy and obesity. In healthy control mice, empagliflozin had no functional effect. Chronic in vivo empagliflozin treatment in db/db + Aldo also normalized the changes in cardiomyocyte electrophysiology and Ca²⁺ handling properties measured in the absence of empagliflozin in the perfusion solution during cell experiments, indicating a true phenotypic rescue. Differentially expressed gene clusters were identified characteristic of the db/db genotype, aldosterone, and empagliflozin treatments. Interestingly, empagliflozin did not just reverse the HFpEF-altered gene expression but shifted it further away from control to a new expression profile. We conclude that chronic in vivo empagliflozin treatment restores cardiomyocyte electrophysiological and ECC properties, ameliorates diastolic function in cardiometabolic HFpEF, and induces complex gene expression changes.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"669-688"},"PeriodicalIF":9.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-dependent effects and mechanisms of exercise-like stimulation on cardiac injury and contractile function: outcomes of the MICRO-ATHLETE study.","authors":"Tom T J Luiken, Carla Cofiño-Fabres, José M Rivera-Arbeláez, Danique Snippert, Ellen J S Denessen, Sacha K Lamers, Nicoleta Cius, Koen van den Dries, Alma M A Mingels, Dick H J Thijssen, Robert C J J Passier, Thijs M H Eijsvogels","doi":"10.1007/s00395-026-01182-9","DOIUrl":"10.1007/s00395-026-01182-9","url":null,"abstract":"<p><p>Observational studies revealed that exercise produces cardiac troponin release and cardiac fatigue in athletes. However, human in vivo studies offer limited insights into the underlying mechanisms of these potential deleterious effects. This study investigated exercise-induced cardiac troponin release, cardiac fatigue, and its potential mechanisms in a versatile in vitro Engineered Heart Tissue (EHT) model. EHTs were subjected to exercise-like electrical pulse stimulation (EL-EPS) at 2.5 Hz (150 bpm) for 2 or 4 h and compared to non-stimulated controls and doxorubicin (DOX)-exposed tissues. High-sensitive cardiac troponin T (hs-cTnT), lactate dehydrogenase (LDH), and cardiomyocyte contractile function were measured at baseline, immediately after EL-EPS, and after 20 h of recovery. Cell death was quantified by nuclear and mitochondrial DNA concentrations and tissue integrity was assessed using microscopy following exposure. Following 2 and 4 h of EL-EPS, and after DOX exposure, we found increased hs-cTnT and LDH levels and reduced contractile function compared to control. After recovery, contractile function remained impaired after 4 h EL-EPS and DOX exposure, whereas the effects were abolished after recovery for the 2 h EL-EPS group. Elevated nuclear and mitochondrial DNA release was found following DOX, but not after 2 and 4 h EL-EPS. Finally, EL-EPS was associated with the formation of actin aggregates. EL-EPS induced dose-dependent increases in hs-cTnT and LDH concentrations in conjugation with signs of cardiac fatigue, but without elevated markers of permanent cell death (i.e., mitochondrial/nuclear DNA). These findings suggest that exercise-induced elevations of cardiac biomarker concentrations are indicative of reversible cardiac injury.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"725-737"},"PeriodicalIF":9.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional consequences of diminished myocardial oxygen delivery per beat in experimental heart failure.","authors":"Salman I Essajee, Matthew J Eden, Victoria E Sturgess, Gregory M Dick, Selina M Tucker, Cooper M Warne, C Alberto Figueroa, Daniel A Beard, Johnathan D Tune","doi":"10.1007/s00395-026-01186-5","DOIUrl":"10.1007/s00395-026-01186-5","url":null,"abstract":"<p><p>This investigation was designed to test the hypothesis that heart failure (HF) attenuates coronary vasodilation and autoregulation and that deficits in contractile function are proportionally related to reductions in the volume of myocardial perfusion and oxygen delivered per beat. Utilizing a pacing-induced model of HF in Ossabaw swine, we determined that chronic pacing at 180 beats/min for ~ 4 weeks significantly reduced baseline coronary flow by ~ 45% (P = 0.01), lowered myocardial oxygen consumption (MVO₂) (P = 0.07) and systolic wall thickening by ~ 30% (P < 0.01), and increased left ventricular end-diastolic pressure ~ 160% (P < 0.05). Coronary flow responses to Regadenoson (0.4 mg) and cardiac pacing (180 beats/min) were significantly attenuated in swine with pacing HF (P ≤ 0.01). Control swine displayed relatively strong autoregulatory capability with coronary flow decreasing ~ 10% (P = 0.26) as blood pressure was pharmacologically reduced from 120 to 60 mmHg. Alternatively, coronary flow decreased ~ 40% (P = 0.01) over the same pressure range in pacing HF swine. Regional wall thickening and stroke volume declined once myocardial oxygen delivery fell below ~ 1.0 µL O₂/g/beat. These findings indicate that adaptations in the coronary microcirculation in pacing HF attenuate coronary metabolic and autoregulatory capacity and that subsequent functional deficits are related to reductions in the volume of myocardial perfusion and oxygen delivered per beat.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"711-723"},"PeriodicalIF":9.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}