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Journal articleCheng K, Rajabali H, Tan S-T, et al., 2025,
Procedural factors influencing successful coronary sinus reducer implantation for refractory angina: a single-centre experience
, Cardiovascular Revascularization Medicine, Vol: 78, Pages: 65-72, ISSN: 1553-8389BackgroundCoronary sinus reducer (CSR) implantation is emerging as a novel effective percutaneous therapy for patients with refractory angina. Limited data exists examining the factors influencing successful CSR implantation. As CSR implantation becomes more widely adopted, a greater understanding of the procedural challenges which operators encounter is required.AimTo evaluate the patient and procedural characteristics influencing successful CSR implantation.MethodsThis was a retrospective cohort study of consecutive patients with refractory angina undergoing clinically indicated CSR implantation (February 2016 to August 2024) at a high-volume implanting centre in the UK. Patient and procedural characteristics affecting procedural difficulty were systematically analysed. Procedural difficulty was determined by 1) increasing total procedural time or 2) features of challenging equipment handling such as bellying, swan-necking or complete equipment fallout from the coronary sinus (CS).Results102 out of 105 (97 %) patients underwent a successful CSR implant at the first attempt. Patients had a high rate of previous revascularisation (PCI: 85 %; CABG 64 %) and diabetes (58 %). Significant improvements in Canadian Cardiovascular Society (CCS) class were observed with 36 % of patients improving by ≥2 CCS classes and 71 % improving by ≥1 CCS class. A C- or non-C-shape of the CS was not associated with differences in procedural time (P = 0.52). However, the presence of both a valve and ridge in the CS was associated with significantly longer procedural times (P = 0.03). A ridge, alone or together with a valve, predicted features of procedural difficulty, such as bellying (ridge – OR: 2.69, P = 0.02; valve and ridge – OR: 4.58, P = 0.0006) and swan-necking (ridge – OR: 5.43, P = 0.001; valve and ridge – OR: 4.74, P = 0.002). Bellying, swan-necking, and complete fallout of equipment from the CS were associated with longer procedural times, but al
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Journal articleWinkler M, Staniczek T, Suhayda M, et al., 2025,
Endothelial c-Maf prevents MASLD-like liver fibrosis by regulating chromatin accessibility to suppress pathogenic microvascular cell subsets
, JHEP Reports, Vol: 7, ISSN: 2589-5559Background & AimsLiver sinusoidal endothelial cells (LSECs) are highly specialized components of the hepatic vascular niche, regulating liver function and disease pathogenesis through angiocrine signaling. Recently, we identified GATA4 as a key transcription factor controlling LSEC development and protecting against liver fibrosis. As the transcription factor c-Maf was strongly downregulated in Gata4-deficient LSECs, we hypothesized that c-Maf might be an important downstream effector of GATA4 in LSEC differentiation and liver fibrogenesis.MethodsClec4g-iCre/Maffl/fl (MafLSEC-KO) mice with LSEC-specific Maf deficiency were generated and liver tissue was analyzed histologically. LSECs were isolated for bulk RNA-seq, ATAC-seq, and single-cell (sc) RNA-seq analysis. MafLSEC-KO livers were analyzed after MASH diet feeding. The expression of MAF and its targets was analyzed in published human scRNA-seq data.ResultsEndothelial Maf deficiency resulted in perisinusoidal liver fibrosis (Sirius red 0.46% vs. 2.92%; p <0.05) without affecting metabolic liver zonation, accompanied by a switch from sinusoidal to continuous endothelial cell identity, which was aggravated upon MASH diet feeding (p <0.01). Furthermore, endothelial Maf deficiency caused LSEC proliferation (p <0.05) and expression of profibrotic angiocrine factors including Pdgfb, Igfbp5, Flrt2, and Cxcl12, among which FLRT2 (p <0.01) and CXCL12 (p <0.001) activated hepatic stellate cells in vitro. scRNA-seq revealed replacement of zonated LSEC subpopulations with capillarized, proliferative, sprouting and secretory endothelial cell subsets that promote liver fibrogenesis and angiogenesis. This fundamental dysregulation of LSEC gene expression and differentiation was caused by changes in chromatin accessibility and transcription factor activity following loss of Maf. Notably, endothelial MAF expression was also significantly reduced in human cirrhotic livers (p <0.0001).ConclusionsHepatic endoth
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Journal articleZhao L, Wilkins MR, 2025,
Zinc, Soluble Epoxide Hydrolase, and the Pulmonary Vascular Paradox: Novel Insights into a Well-Known Phenomenon
, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 211, Pages: 1551-1552, ISSN: 1073-449X -
Journal articleBacila IA, Lawrence NR, Alvi S, et al., 2025,
Leptin and adiponectin in children and young persons with congenital adrenal hyperplasia
, European Journal of Endocrinology, Vol: 193, Pages: 329-339, ISSN: 0804-4643ObjectivesPatients with congenital adrenal hyperplasia (CAH) have increased prevalence of metabolic problems. We studied adiponectin, leptin and resistin in children with CAH, in relation to BMI, treatment, hormonal and metabolic biomarkers.Design and MethodsWe analysed 101 patients with 21-hydroxylase deficiency (54 females, 13.0 ± 2.92 years) from 13 centres in the United Kingdom, and 83 sex- and age-matched controls. Blood parameters (leptin, adiponectin, resistin, metabolic and hormonal markers) were measured in fasted state, between 09:00 and 11:00, after the first glucocorticoid (GC) dose.ResultsA difference in adipokines between patients and controls was only found for leptin in males (patients > control, P = .033). In patients and controls, leptin had a positive relationship with BMI-SDS (P < .001). However, adiponectin decreased with the BMI only in patients (P < .001). Contrary to published evidence on the effect of synthetic steroids on leptin, in our cohort, leptin decreased with the increasing first daily hydrocortisone (HC) dose (Log10Leptin = 4.1– 0.08xfirstGCdose (mg/m2), P = .009) but not with the total daily dose. When correcting for BMI, a positive relationship between leptin and insulin was only found in controls (P < .001). Adiponectin decreased with steroid precursor and androgen concentrations (17-hydroxyprogesterone, androstenedione, testosterone, 11-hydroxyandrostenedione, 11-ketotestosterone) in patients.ConclusionOur findings indicate a decrease in leptin with the HC dose, consistent with a detrimental effect of glucocorticoid on satiety and hunger pathways in CAH. Adiponectin was decreased in patients with increased androgens concentrations, suggesting it may be used as an indicator of metabolic risk associated with poor hormonal CAH control.
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Journal articleRothman AMK, Benza R, Wilkins MR, et al., 2025,
Remote monitoring in pulmonary arterial hypertension
, Ers Monograph, Vol: 2025-September, Pages: 77-83, ISSN: 2312-508XPAH is a progressive chronic condition requiring regular hospital-based assessments to guide therapy. These infrequent snapshot evaluations limit timely intervention and personalised care. Remote monitoring technologies offer real-time, high-frequency collection of key physiological parameters and patient-reported outcomes from patients’ homes and have transformed the management of heart failure, diabetes and cardiac arrhythmias. In clinical research, these tools reduce bias, enhance statistical power and support innovative study designs, including small decentralised trials with continuous assessment of therapeutic response. Clinically, remote monitoring supports faster, more informed treatment adjustments and improves engagement between patients and care teams. As infrastructure and data management systems evolve, remote monitoring could become central to both clinical studies and the routine care of patients with PH, enabling earlier intervention and improved outcomes.
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Journal articleYarmolinsky J, Lee MA, Lau E, et al., 2025,
Proteogenomic and observational evidence implicate ANGPTL4 as a potential therapeutic target for colorectal cancer prevention
, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 117, Pages: 1836-1847, ISSN: 0027-8874- Cite
- Citations: 1
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Journal articleBen-Aicha S, Shmool TA, Emanueli C, 2025,
RNA Therapeutics for In Vivo CAR-Macrophage: Advancing Cardiac Immunotherapy
, CIRCULATION RESEARCH, Vol: 137, Pages: 860-862, ISSN: 0009-7330 -
Journal articlevan der Velpen V, Haner JD, Kakizaki R, et al., 2025,
Intake of high-intensity statin after acute myocardial infarction assessed by direct drug concentration measurement: association with LDL-C response and coronary plaque modifications in the PACMAN-AMI trial
, EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY, ISSN: 2047-4873 -
Journal articleCho H-J, Smith J, Switzer CH, et al., 2025,
SFX-01 is therapeutic against myeloproliferative disorders caused by activating mutations in Shp2
, EMBO MOLECULAR MEDICINE, Vol: 17, Pages: 2115-2136, ISSN: 1757-4676 -
Journal articleGiannini F, Ponticelli F, Konigstein M, et al., 2025,
Impact of Coronary Sinus Reducer on Angina Symptoms in Patients With Myocardial Ischemia Without Obstructive Coronary Artery Disease
, CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, ISSN: 1522-1946 -
Journal articleCheng K, de Silva R, 2025,
Managing angina across the spectrum of non-acute myocardial ischaemic syndromes
, Trends in Cardiovascular Medicine, Vol: 35, Pages: 351-353, ISSN: 1050-1738 -
Journal articleRothman AMK, Villar S, Law M, et al., 2025,
A Promising Therapeutic Shining Light on Pulmonary Arterial Hypertension Treatment
, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 211, Pages: 1533-1534, ISSN: 1073-449X -
Journal articleThomas AN, Kalakoutas A, Yates M, et al., 2025,
Mitochondrial dysfunction contributes to sustained muscle loss after cardiac surgery: a prospective observational study
, Journal of Cachexia, Sarcopenia and Muscle, Vol: 16, ISSN: 2190-5991BackgroundAs a major systemic insult, cardiac surgery can lead to significant muscle loss, which increases the time to recovery as well as being correlated with mortality. Highly variable loss of muscle mass (0%–40% rectus femoris cross-sectional area [RFcsa]) and strength in the week after surgery has aided understanding of mechanisms of sarcopenia after acute illness. To include muscle recovery, patients' muscle phenotype beyond the first week after surgery and up to their return as outpatients was studied and correlated with protein and metabolomic markers.MethodsPatients undergoing elective aortic valve surgery were recruited. Muscle mass (RFcsa), strength (handgrip, knee extension and spirometry), body composition (by bioimpedance) and health-related quality of life (generic questionnaire EQ-5D-5L) were determined pre-operatively, 7 days after surgery and at outpatient follow-up. Blood samples were taken on Days 0, 1, 3, 7 and follow-up. The plasma metabolome was determined in 20 patients at Days 0, 3, 7 and follow-up.ResultsOf 31 participants, 20 were male: mean age 68.8 years with a range between 48 and 85 years. Proportionate mean loss of RFcsa between pre-op and Day 7 values was 6.44% [95% CI 4.21 to 8.68, n = 31]; between pre-op and follow-up 9.69% [95% CI 4.92 to 14.96, n = 22]; and between Day 7 and follow-up 3.60% [95% CI −1.30 to 8.48, n = 22]. By contrast to measures of muscle bulk, the strength and functionality assessments (knee extension, handgrip, spirometry and short physical performance battery) decreased in the first week after surgery (pre-op to Day 7) followed by a return to baseline (Day 7 to follow-up). Health-related quality of life (cross-walk index) changed little over the course of the study but correlated positively at follow-up with muscle bulk (RFcsa: r = 0.58 [95% CI 0.19 to 0.81] p = 0.005) and strength of knee extension (r&thinsp
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Journal articleKemp PR, Griffiths M, Polkey MI, et al., 2025,
Variability in sensitivity to inflammation in muscle and lung of patients with COPD may underlie susceptibility to lung function decline
, Thorax, Vol: 80, Pages: 520-529, ISSN: 0040-6376Background: Muscle wasting and weakness (sarcopenia) are commonly associated with COPD causing frailty and reduced quality of life. The contribution of inflammation to muscle loss and the susceptibility to rapid lung function decline is debated. We hypothesised that comparing the muscle transcriptome to circulating inflammatory cytokine profiles in patients would identify any contribution of systemic inflammation to muscle atrophy.Methods: Quadriceps differential gene expression was determined between mild-COPD (n=28) and severe-COPD (n=51) using GSE100281. These microarray data were compared by biweight mid-correlation with lung function and plasma cytokine levels from the same patients.Results: Patients with severe COPD had reduced fat-free mass index (a measurement of muscle mass) compared with patients with mild COPD despite similar physical activity and inflammatory cytokine levels. Gene sets associated with inflammation and epithelial mesenchymal transition (EMT) were elevated in severe COPD, suggesting that inflammation may contribute to the loss of muscle mass. In patients with severe COPD, EMT and inflammation gene sets were strongly associated with circulating proinflammatory and anti-inflammatory cytokines. However, in patients with mild COPD, anti-inflammatory cytokines showed negative associations with these gene sets and associations with proinflammatory cytokines were weak. In data from lung and blood samples, patients with severe COPD had elevated inflammatory and EMT gene expression compared with patients with mild COPD suggesting that this phenomenon is not muscle-specific.Conclusions: In patients at the severe end of the COPD spectrum, the proinflammatory response in muscle predominates, whereas in patients at the mild end of the spectrum, the anti-inflammatory response predominates. This suggestion needs confirming in a longitudinal cohort.
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Journal articleBoucly A, Song S, Keles M, et al., 2025,
Clustering pulmonary hypertension patients using the plasma proteome
, American Journal of Respiratory and Critical Care Medicine, Vol: 211, Pages: 1492-1503, ISSN: 1073-449XIntroduction: Patients with pulmonary hypertension are classified according to clinical criteria to inform treatment decisions. Knowledge of the molecular drivers of pulmonary hypertension might better inform treatment choice. Methods: Between 2013 and 2021, 470 patients with pulmonary hypertension, 136 disease controls and 59 healthy controls were enrolled as a discovery cohort. Plasma levels of 7288 proteins were assayed (SomaScan 7K platform). Proteins that distinguished pulmonary hypertension from both control groups were selected for unsupervised clustering (k-means clustering of UMAP dimensions). Clinical characteristics and outcomes were compared across clusters. Separate cohorts of serially sampled patients from pulmonary hypertension centers in the United Kingdom (n=229) and France (n=79) provided independent validation. Results: 156 plasma proteins that distinguished pulmonary hypertension from disease and healthy controls formed 4 clusters with diverse 5-year survival rates: 78% (cluster 4), 62% (cluster 2), 44% (cluster 3), and 33% (cluster 1). The distinction and clinical relevance of the clusters were confirmed in validation cohorts by their association with survival. To further characterise the therapeutic relevance of the clusters we investigated 2 experimental drug targets: the Platelet-Derived Growth Factor (PDGF) pathway was up-regulated in cluster 3 compared to other clusters and the Transforming Growth Factor-β (TGF-β) pathway was up-regulated in cluster 1. Conclusion: Plasma proteomic profiling of patients with pulmonary hypertension distinguishes 4 clusters, independent of the clinical classification. These groups, based on differential plasma protein levels, could act as theragnostic biomarkers for new therapies targeting PDGF and TGF-β pathways. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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Conference paperSerbulea V, Salamon A, Milosek V, et al., 2025,
Pyruvate Dehydrogenase Inhibition Induces a Metabolic Shift in SMCs to Enhance Plaque Stability in Atherosclerosis
, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7330 -
Journal articleKwapiszewska G, Rhodes C, Rabinovitch M, et al., 2025,
Pathogenic Concepts in Pulmonary Arterial Hypertension Revisited A Multigenerational Perspective
, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 73, Pages: 200-209, ISSN: 1044-1549 -
Conference paperSchmidt L, Burnap S, Singh B, et al., 2025,
Poster Topic: AS02 LIPIDS AND LIPOPROTEINS / AS02.11 Other Beyond LDL-C: Integrative proteomics and lipidomics analysis in PACMANAMI
, 93rd Congress of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150 -
Conference paperTakov K, Schmidt L, Yeang C, et al., 2025,
Lipoprotein(a) is an apoe-containing particle enriched in triglyceride species associated with incident cardiovascular disease
, 93rd Congress of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150 -
Conference paperYin S, Mayr U, Barallobre-Barreiro J, et al., 2025,
Proteomics highlights the role of hyalectan remodelling in calcific aortic valve disease
, 93rd Congress of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150
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