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Journal articleKardys I, Mayr M, Mair J, et al., 2026,
Proteomics profiling for cardiovascular risk prediction: transforming clinical care.
, Eur Heart J Acute Cardiovasc Care, Vol: 15, Pages: 481-483 -
Journal articleIssitt T, Kagugbe GW, Toe QK, et al., 2026,
Iron Compartmentalisation and Vascular Endothelial Cell Dysfunction.
, Antioxidants (Basel), Vol: 15, ISSN: 2076-3921Iron is essential for life, but its safe use by the body depends on it being kept within tightly controlled compartments. When this compartmentalisation is disrupted-through haemolysis, saturation of scavenger proteins, or dysregulation of the hepcidin-ferroportin axis-damaging iron species accumulate in the circulation and within vascular cells, with potentially serious consequences for endothelial function. This review explores the mechanisms by which iron dysregulation compromises vascular endothelial cell biology across a range of disease states, including haemolytic anaemias, atherosclerosis, cerebrovascular disease, extracorporeal circulatory support, and iatrogenic iron loading. Common pathological themes emerge: depletion of nitric oxide bioavailability, oxidative stress, endothelial activation, and in chronic settings, vascular remodelling. The review subsequently focuses in depth on the pulmonary vasculature, where dysregulated iron compartmentalisation has emerged as a key contributor to the pathogenesis of pulmonary hypertension. Here, iron-driven mitochondrial dysfunction, smooth muscle cell proliferation, and iron-dependent lipid peroxidation via ferroptosis are discussed as mechanistic drivers of pulmonary vascular remodelling. The therapeutic implications of targeting iron handling in pulmonary hypertension are considered, including modulation of the hepcidin-ferroportin axis. Together, the evidence presented highlights disordered iron compartmentalisation as a unifying pathological thread across vascular disease and a compelling target for intervention.
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Journal articleAlharbi R, Keles M, Fernandez N, et al., 2026,
KLF6 activation marks an angiogenic and apoptosis resistant endothelial phenotype in pulmonary arterial hypertension
, Communications Biology, ISSN: 2399-3642 -
Journal articleBarallobre-Barreiro J, Mayr M, 2026,
Proteomic insights into bi-atrial remodelling in persistent atrial fibrillation.
, Cardiovasc Res, Vol: 122, Pages: 958-959 -
Journal articleMarchetti M, Meloni M, Anwar M, et al., 2026,
Correction: Marchetti et al. MicroRNA-24-3p Targets Notch and Other Vascular Morphogens to Regulate Post-ischemic Microvascular Responses in Limb Muscles. Int. J. Mol. Sci. 2020, 21, 1733.
, Int J Mol Sci, Vol: 27In the original publication [...].
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Journal articleNiederer SA, Balmus M, Burr C, et al., 2026,
Digital twins for cardiopulmonary medicine: the case for pulmonary arterial hypertension.
, Am J Respir Crit Care Med, Vol: 212, Pages: 1203-1213The management of pulmonary arterial hypertension (PAH), like so many diseases, currently relies on episodic data from clinic visits, which offers limited insight into a patient's disease trajectory and dynamic clinical decisions. Patient digital twins present a technological solution that combines hospital and community data into a single dynamic and predictive virtual representation of the patient. Digital twins operationalize real-world observational inference at the individual level, functioning as a complementary decision-support tool alongside trial evidence. This review introduces the concept of a patient digital twin and provides a roadmap for the development, evaluation, and potential implementation of a patient digital twin for PAH. The resulting twin has the potential to change PAH care pathways, shifting PAH care from reactive to proactive management.
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Journal articleLundby A, Van Eyk JE, Mayr M, et al., 2026,
Consensus statement on mass spectrometry-based proteomic analysis of cardiac tissue.
, Nat Cardiovasc Res, Vol: 5, Pages: 526-540Mass spectrometry-based cardiac proteomics provides direct molecular insight into cardiac physiology and disease. While plasma proteomics has advanced biomarker discovery, the analysis of cardiac tissue is essential for mechanistic understanding and therapeutic target identification; however, proteomic investigation of cardiac tissue faces unique challenges, including limited sample availability, regional heterogeneity, variability in collection and processing, and inconsistent reporting practices that hinder reproducibility and data integration. Here, we provide a practical framework for designing and conducting mass spectrometry-based proteomic studies of cardiac tissue and primary cardiac cells. We outline best practices and key considerations for sample handling, experimental design, data acquisition, quality control and statistical analysis. This guideline aims to support cardiac researchers in generating robust and reproducible proteomics datasets that advance our understanding of cardiac biology in both physiological and pathological contexts.
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Journal articlePericleous C, Strauss E, Arachchillage DJ, 2026,
Endothelial dysfunction in APS: advancing pathophysiological understanding to improve management.
, Curr Opin Immunol, Vol: 100Endothelial dysfunction (ED) is a hallmark of antiphospholipid syndrome (APS) driven by chronic antiphospholipid antibody (aPL) exposure. Beyond acute thrombotic events, ED contributes to atherosclerosis, vascular remodelling, stenosis and multi-organ manifestations, positioning the endothelium as a putative target for disease monitoring and therapeutic intervention. In this review, we integrate new experimental and clinical studies with emerging data presented at recent international meetings that advance our understanding of endothelial pathophysiology in APS. These studies reveal novel APS vascular endotypes and convergence between aPL-driven endothelial thromboinflammation, endothelial-to-mesenchymal transition, extracellular matrix remodelling and aberrant cell growth pathways across arterial, venous and capillary territories, and multiple organs. We discuss evolving approaches to assess endothelial health, including circulating biomarkers, endothelial colony-forming cells, and non-invasive functional and imaging-based tools. Finally, we highlight the need to integrate early detection, aggressive cardiovascular risk modification and precision medicine to mitigate ED and improve long-term outcomes in APS.
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Journal articleToe QK, Issitt T, Quinlan GJ, et al., 2026,
The Interplay Between IL-6, Hepcidin, and BMPR2 Signalling in Pulmonary Arterial Hypertension: Mechanistic Insights Into Vascular Remodelling.
, Pulm Circ, Vol: 16, ISSN: 2045-8932Pulmonary arterial hypertension (PAH) is characterized by excessive pulmonary vasoconstriction and vascular remodelling, with mutations in bone morphogenetic protein receptor type 2 (BMPR2) being the most common genetic alteration associated with the disease. While inflammatory mediators like interleukin-6 (IL-6) and the iron-regulatory hormone hepcidin have been implicated in vascular remodelling, their interaction with BMPR2 signalling remains poorly understood. This study investigated how IL-6 and hepcidin influence BMPR2 expression and downstream signalling in human pulmonary arterial endothelial cells (hPAECs). Using qPCR and Western blot analyses, we demonstrated that both IL-6 and hepcidin significantly reduced BMPR2 mRNA and protein levels in hPAECs. Intriguingly, despite this reduction, SMAD1/5 phosphorylation remained active, suggesting compensatory signalling through alternative receptor complexes. Treatment with IL-6 and hepcidin upregulated inhibitors of differentiation (ID) protein expression, mimicking the effects observed with BMPR2 knockdown. These findings reveal a novel regulatory axis involving IL-6, hepcidin, and BMPR2 in PAH pathogenesis, where IL-6 and hepcidin promote vascular remodelling through both BMPR2-dependent and independent mechanisms. These results suggest that therapeutic strategies targeting this axis, particularly those aimed at rebalancing BMP/TGF-β signalling, may hold promise for treating PAH.
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Journal articleNaser J, Fogell NA, Patel M, et al., 2026,
Experimental comparisons of optical coherence tomography-based versus angiography-based time-averaged wall shear stress estimations.
, Int J Cardiovasc Imaging, Vol: 42, Pages: 1029-1043An approach to rapid simulation of time-averaged wall shear stress (TAWSS) on 3D geometries created from 3D Quantitative Coronary Angiography (3D-QCA) methodology has been developed, which enables rapid computational fluid dynamic (CFD) shear stress simulation. We compared TAWSS estimated from 3D-QCA-CFD with optical coherence tomography (OCT)-based CFD simulations in coronary arteries. 15 normal and 5 stenotic coronary arteries in instrumented minipigs were studied. 3D arterial geometries were reconstructed from 3D-QCA and OCT using common centrelines and matched axial positions. Identical boundary conditions were used for both methods through directly measured vessel-specific inlet blood velocities. TAWSS was calculated for axially matched segments (n = 80 for normal arteries; n = 160 for stenotic arteries) and in 3 mm/60° sectors. Mean TAWSS simulation times for 3D-QCA and OCT-based CFD were 17.8 min and ~ 1.5 h respectively. There were significant but numerically small differences in TAWSS for normal arteries (-0.21 ± 0.64 Pa [95%CI -1.04,1.46], p < 0.001), and no significant difference for stenotic arteries (-0.39 ± 3.04 Pa [95%CI -6.35, 5.56], p = 0.25). Axial TAWSS profiles along vessel lengths were similar between the two methods. There is a trend of underestimation by 3D-QCA at higher values of TAWSS compared with OCT, due to differences in geometry dimensions. Similar spatial distributions of TAWSS in both normal and stenotic arteries were observed from co-registered TAWSS maps. This study suggests that 3D-QCA-based TAWSS is feasible in both normal and stenotic arteries and that further clinical evaluation of rapid TAWSS from 3D-QCA is warranted, which may facilitate clinical adoption of TAWSS assessment.
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Journal articleSamaranayake CB, Niglas M, Baxan N, et al., 2026,
Hemodynamic and metabolomic responses to infusion of GLP-1 agonist exenatide in pulmonary arterial hypertension
, JCI Insight, Vol: 11, ISSN: 2379-3708Preclinical studies suggest beneficial effects of GLP-1 agonists in pulmonary arterial hypertension (PAH). This first-in-disease study evaluated acute hemodynamic effects of GLP-1 agonist, exenatide administered i.v. in patients with idiopathic PAH and CTEPH as well as in a PAH rodent model. Seventeen patients (9 idiopathic PAH) received an exenatide infusion during right heart catheterization, which included multisite sampling for circulating metabolites. Acute effects of exenatide were also assessed by cardiac magnetic resonance imaging in monocrotaline (MCT) PAH and control rats. In the clinical study, exenatide was well tolerated, reduced mean pulmonary artery pressure (45 ± 15 mmHg versus 40 ± 18 mmHg), and improved cardiac index (2.1 ± 0.6 L/min versus 2.4 ± 0.9 L/min/m2) and pulmonary vascular resistance (7.8 ± 8.0 WU versus 5.9 ± 5.0 WU) across all patients. Right ventricular (RV) contractility and afterload improved in a subset of patients undergoing pressure-volume measurements. In an exploratory metabolomics analysis, 47 metabolite levels changed after exenatide infusion, predominantly in free fatty acid pathways. Six metabolites with prognostic relevance in PAH within myocardial glycolytic and lipid oxidation pathways were also altered after exenatide. In MCT rats, exenatide improved RV stroke-volume, RV ejection fraction, and RV-arterial coupling. These findings support the further evaluation of exenatide within chronic studies as a potentially novel pulmonary vasodilator therapy.
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Journal articleConstantinescu-Bercu A, Smith KE, Wong SY, et al., 2026,
Von Willebrand factor deficiency impairs angiogenesis via angiopoietin-2: relevance for gut angiodysplasia
, Blood Journal, Vol: 147, Pages: 2541-2553, ISSN: 0006-4971Management of recurrent gastrointestinal (GI) bleeding is a clinical unmet need for patients with von Willebrand disease (VWD) and is linked to the presence of gut vascular malformations (angiodysplasia). We previously demonstrated that von Willebrand factor (VWF) regulates angiogenesis and vascular integrity. VWF controls the storage of the angiogenesis regulator angiopoietin-2 (Angpt-2) in endothelial cells (EC), suggesting a candidate for the genesis of angiodysplasia; however, no direct evidence of the role of Angpt-2 in VWF-dependent angiogenesis is available. Using VWF-deficient human umbilical vein EC (HUVEC) and endothelial colony-forming cells (ECFCs) from patients with severe VWD, we found that loss of VWF resulted in increased Angpt-2 expression through the positive feedback loop Angpt-2–Tie-2–Akt–FOXO1–Angpt-2. In the gut of VWF-deficient mice, Angpt-2 expression was increased, whereas Angpt-1 expression was decreased, suggesting that VWF regulates the Angpt/Tie2 balance in the gut. Moreover, the intestinal vasculature in the jejunum of VWF-deficient mice appeared abnormal, with hypersprouting and lumen formation defects. The findings reveal VWF-deficient mice as a model to study gut angiodysplasia. We investigated sprouting angiogenesis in vitro using a fibrin bead assay and found increased sprouting in VWF-deficient EC. We developed a 3-dimensional microfluidic model of angiogenesis and found that ECFCs from patients with severe VWD exhibit defective remodeling and abnormal lumen formation, reminiscent of the defects in the gut of VWF-deficient mice. Importantly, inhibition of Angpt-2 reduced sprouting in VWF-deficient HUVEC and normalized vascular remodeling in VWD-ECFCs, suggesting that Angpt-2 inhibitors may be effective in patients with VWD with GI bleeding and angiodysplasia.
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Journal articleJones RJ, De Bie EMDD, Deliu N, et al., 2026,
Sotatercept reduces bone morphogenetic protein signaling in patients with pulmonary arterial hypertension.
, Sci Transl Med, Vol: 18Pulmonary arterial hypertension (PAH) is a rare, life-limiting disease where imbalances in the transforming growth factor-β (TGF-β) and bone morphogenetic protein receptor type II (BMPR-II) superfamily pathways have causal roles in hereditary and idiopathic forms of the disease. These pathways are emerging attractive candidates for therapeutic intervention, but there is an unmet need for clinically relevant and practical biomarkers that can measure target engagement, partly because of the inaccessibility of lung tissue in disease for molecular profiling. Here, we explored the surrogate capacity of peripheral blood bone morphogenetic protein (BMP) pathway-specific markers using samples collected in the StratosPHere 1 study using both cell surface assessment of BMPR-II receptor levels and quantitative PCR for the assessment of downstream target engagement. Downstream BMPR-II canonical and noncanonical signaling was measurable and altered in whole blood in both discovery and international replication cohorts, and transcriptomic signatures were clustered by discrete gene modules that associated with clinical outcomes and mortality. We derived a transcriptomic biomarker panel that was repeatable, reproducible, and longitudinally stable for use in early phase, target engagement clinical trials. The biomarker panel was used in a pilot study of nine sotatercept-treated patients with PAH to test the effect of the therapy on the BMP pathway; analysis suggested that sotatercept did not rebalance or increase BMPR-II pathway signaling but rather led to a reduction, possibly due to depletion of circulating BMP9 and BMP10.
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Journal articlePisacano N, Evans RA, Nutley AS, et al., 2026,
Actin regulation of neutrophil effector mechanisms in health and disease.
, J Leukoc Biol, Vol: 118Neutrophils are central to immune responses in health and disease, and their ability to deform correlates with their functional responses. In health, reorganization of the neutrophil cytoskeleton allows neutrophils to carry out their effector mechanisms. However, in the disease state, dysregulation of neutrophil cytoskeletal properties results in disruption of neutrophil structural integrity, in turn altering their immune response capabilities. We outline how actin and actin polymerization are essential for cell processes, the role of actin in neutrophil function, and how disruption of actin can lead and contribute to a range of disease pathogeneses.
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Journal articlePerry RN, Lenert G, Benavente ED, et al., 2026,
Female-Biased VSMC GRNs Predict MYH9 as Regulator of Fibrous Plaque Phenotype.
, Circ Res, Vol: 138BACKGROUND: Atherosclerosis, an inflammatory driver of coronary artery disease, manifests as unstable atheromatous plaques and stable fibrous plaques. Although atheromatous plaques have been extensively studied, fibrous plaques, particularly in women aged <50 years, where erosion contributes significantly to coronary thrombosis, remain less understood. The molecular mechanisms underlying sex differences in plaque biology, including vascular smooth muscle cell contributions, are incompletely defined. METHODS: Sex-specific gene regulatory networks (GRNs) were constructed from RNA-sequencing data of cultured human vascular smooth muscle cells isolated from 119 male and 32 female heart transplant donors. Network preservation analyses identified female-biased GRNs, which were evaluated in single-cell RNA-sequencing data sets from human carotid atherosclerotic plaques. Bayesian network modeling and proteomic analyses were used to identify and validate regulatory drivers. RESULTS: Two female-biased vascular smooth muscle cell networks, GRNfloralwhite and GRNyellowgreen, were enriched for inflammatory and actin remodeling pathways, respectively. Single-cell RNA-sequencing confirmed sex-specific network activity in plaque vascular smooth muscle cells. Subcellular phenotyping identified a sex-specific gene expression program within GRNyellowgreen enriched for contractile and vascular development pathways. Bayesian network modeling identified MYH9 (myosin heavy chain 9) as a key driver gene. Elevated MYH9 abundance was associated with increased smooth muscle cell content and reduced lipid content in female carotid plaques compared with males, consistent with fibrous plaque features. Proteomic analyses confirmed MYH9 upregulation in female fibrous plaques and association with stable plaque characteristics. CONCLUSIONS: These findings identify MYH9 as a regulator of female-biased fibrous plaque biology and highlight the importance of sex-specific network regulation in atheros
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Journal articleMoncayo CR, Restuadi R, Zhang G, et al., 2026,
Multimodal imaging reveals a lysosomal drug reservoir that drives heterogeneous distribution of PARP inhibitors
, Nature Communications, Vol: 17, ISSN: 2041-1723For all drugs, effective target engagement requires sufficient intracellular concentrations of drug to be reached, but whether tumour heterogeneity impacts drug distribution and efficacy is poorly studied. Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed treatment opportunities for women with high-grade serous ovarian carcinoma, but resistance remains a clinical hurdle in this highly heterogeneous tumour type. Here, we present a patient-derived explant multi-modal imaging pipeline, which demonstrates that cell-intrinsic PARP inhibitor accumulation is highly variable, both between patients and within tumours. Spatial transcriptomics reveals enrichment of apoptotic and lysosomal signatures in high-drug regions. Rucaparib, an intrinsically fluorescent PARP inhibitor, accumulates heterogeneously at the single-cell level, with rucaparib high cells demonstrating increased drug response relative to rucaparib-low. Mechanistically, lysosomal sequestration creates a rucaparib reservoir that determines drug levels in the nucleus. Perturbation of lysosomal content alters intracellular levels of weak base PARP inhibitors rucaparib and niraparib, but not olaparib. Together these data suggest that lysosomes act as a reservoir for a subset of PARP inhibitor drugs to improve drug response.
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Journal articleBabuta J, Gruevska A, Wickremesinghe C, et al., 2026,
Altered sphingolipid metabolism is associated with osimertinib resistance in non-small cell lung cancer
, Journal of Proteome Research, Vol: 25, Pages: 2569-2580, ISSN: 1535-3893Nonsmall-cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases. Epidermal growth factor receptor mutations (EGFRm) occur in 15 and 40% of NSCLC in Western and Asian populations, respectively. Current treatment for advanced NSCLC targets EGFRm with tyrosine kinase inhibitors (TKIs). Osimertinib is a third-generation EGFR-TKI now used as a first-line treatment in advanced/metastatic NSCLC; however, drug resistance frequently develops. Dysregulation of metabolism has been suggested to play a role in the development of drug resistance. Here, we investigated the role of lipid metabolism in the development of osimertinib resistance (OR) using pharmacologically-induced resistant cellular models. We used a multiomics approach, combining lipidomics with proteomics analyses. We found alterations in processes relating to metabolism, such as dysregulated sphingolipid metabolism. In particular, we identified that OR lines reduce free ceramides in favor of complex glycosphingolipids. Mechanistically, this metabolic shift avoids ceramide-mediated apoptosis via caspase-3 activation. Importantly, when we combined osimertinib with D-PDMP, an inhibitor of the key enzyme responsible for the conversion of ceramide to glucosylceramide, we increased the sensitivity to osimertinib. Overall, we have identified the glycosphingolipid metabolic pathway as a potential therapeutic target to reinstate sensitivity to osimertinib in NSCLC.
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Journal articleFeneck EM, Morgan J, Baig F, et al., 2026,
Abnormal extracellular matrix deposition by fascial fibroblasts underlies the connective tissue pathology in the disease Radial Dysplasia.
, Matrix Biol, Vol: 145, Pages: 19-31Fibroblast cells are broadly distributed throughout the body and play instructive roles in tissue development and homeostasis. Defects in fibroblast function have been associated with developmental disorders, cancer and inflammatory disease. Our results reveal a previously unappreciated defect of fascial fibroblasts in patients with the upper limb congenital abnormality, Radial Dysplasia (RD). We identify compositional abnormalities in the extracellular matrix secreted by RD fascia-derived fibroblasts and provide an explanation for the consequent disorganisation and altered material properties of RD fascia and how this may impact disease pathology and patients' response to treatment. We show the abnormalities of RD fascial fibroblasts are reversible in vitro and identify a pathway with therapeutic potential to treat the soft tissue defects associated with RD. More broadly, our results have implications for understanding how heterogeneous tissue-resident fibroblast populations and the ECM they secrete contribute to normal tissue formation, homeostasis and disease.
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Journal articleAherrahrou R, Reinberger T, Werner J, et al., 2026,
Deficiency of ZC3HC1 Modulates Vascular Smooth Muscle Cell Phenotype and Increases Neointima Formation.
, Arterioscler Thromb Vasc Biol, Vol: 46BACKGROUND: The ZC3HC1 (zinc finger C3HC-type containing 1) gene has been linked to various cardiovascular traits, including coronary artery disease, blood pressure, and carotid intima-media thickness with opposing effects. This study aimed to investigate the role of ZC3HC1 in smooth muscle cell (SMC) biology and its contribution to neointima formation. METHODS: SMC phenotypes (proliferation and migration) were analyzed according to rs11556924 genotype, small interfering RNA-mediated knockdown of human ZC3HC1, or complete knockout of murine Zc3hc1. Transcriptomic profiling and contractile marker expression were used to define SMC states. The impact of complete gene loss on injury-induced neointima formation was examined in vivo using Zc3hc1-/- mice. Subcellular localization of murine NIPA (nuclear interaction partner of anaplastic lymphoma kinase; encoded by Zc3hc1) during the cell cycle was analyzed by immunofluorescence microscopy. RESULTS: The coronary artery disease-protective rs11556924-T allele was associated with reduced ZC3HC1 expression and enhanced SMC migration. ZC3HC1 knockdown in human SMCs replicated this phenotype, increasing migration and proliferation, and leading to CCNB1 (cyclin B1) accumulation with reduced expression of contractile markers. Following arterial injury, Zc3hc1-/- mice exhibited exaggerated neointima formation and enhanced SMC migration. In contrast to small interfering RNA experiments, complete Zc3hc1 loss resulted in reduced SMC proliferation and lower CCNB1 levels. Transient knockdown of Zc3hc1 in wild-type mouse SMCs increased proliferation, recapitulating findings in human cells. Immunofluorescence revealed colocalization of NIPA and CCNB1 at the cleavage furrow, suggesting a role in mitotic exit. CONCLUSIONS: ZC3HC1 acts as a dosage-sensitive modulator of SMC phenotype. Partial reduction promotes a synthetic, proliferative state and neointima formation, while complete loss induces a quiescent phenotype. These findings provide
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Journal articleTikhomirov R, Boichenko V, Reilly-O'Donnell B, et al., 2026,
Interleukin 11-Induced MicroRNAs as Functional Mediators and Circulating Biomarkers of Cardiac Fibrosis.
, Circ Res, Vol: 138BACKGROUND: Cardiac fibrosis can be triggered by several pathologies, including ischemic heart disease and aortic stenosis. Cardiac fibrosis is brought about by uncontrolled ECM (extracellular matrix) deposition by myofibroblasts. IL (interleukin)-11 (Il11) has been demonstrated as a trigger of multiorgan fibrosis. However, the molecular mechanisms underpinning IL-11-induced fibrosis require further characterization. Recent studies indicate that microRNA dysregulation contributes to the pathogenesis of cardiac fibrosis and can be targeted therapeutically. This study explored the hypothesis that microRNAs act as downstream effectors of IL-11-induced cardiac fibrosis. Moreover, we investigated the translational potential of IL-11-regulated microRNAs as circulating biomarkers of cardiac fibrosis in patients with aortic stenosis. METHODS: A bioinformatic microRNA target prediction analysis was used to identify candidate microRNAs regulated by IL-11. Experimental validation was performed in cardiac fibroblasts from postinfarction failing and healthy rat hearts, after IL-11 stimulation. Functional studies assessed the effects of microRNA modulation on fibrotic gene expression in cardiac fibroblasts using microRNA inhibitor-based and mimic-based transfection. Bioinformatic analysis and luciferase assay identified candidate microRNA targets downstream of IL-11. Findings were further evaluated in transverse aortic constriction and cardiomyocyte-specific Il11-overexpression (Tg-Il11 [transgenic mouse model with cardiomyocyte-specific Il11 overexpression]) mouse models and in left ventricular tissue, peripheral plasma, and plasma extracellular vesicles from patients with aortic stenosis. RESULTS: MicroRNA-27b-5p and microRNA-497-5p were identified as novel downstream effectors of IL-11 signaling. IL-11 increased the expression of both microRNAs in cardiac fibroblasts; transfection with either microRNA inhibitor reduced, whereas microRNA mimics increased, profibrotic mRNA level
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