Publications
Results
- Showing results for:
- Reset all filters
Search results
-
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.
-
Journal articleJiang W, Lynam E, Delafosse J, et al., 2026,
ZONAB Regulates DNA Methylation, Mitochondrial Function, and Entry into Cell Senescence of Endothelial Cells
, Cells, Vol: 15, Pages: 1015-1015<jats:p>Regulation of the endothelial stress response is important for blood vessel homeostasis and angiogenesis, processes disrupted in common vascular diseases and ageing. Here, we discovered that the Y-box factor ZONAB (ZO-1-associated nucleic acid binding protein; YBX3), a gene associated with risk loci for severe vascular disorders, regulates endothelial homeostasis and angiogenesis. By combining cell-based assays with primary endothelial cells and genome-wide expression and methylation measurements, we found that ZONAB depletion results in mitochondrial deregulation, increased reactive oxygen species, and a defective oxidative stress response, which correlates with increased promoter methylation of cell cycle genes. ZONAB depletion triggered cellular senescence via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent pathway, which was attenuated by PIK3 inhibitors, an antioxidant, or by drugs targeting mitochondrial function or fragmentation. Thus, our results reveal that ZONAB repression in endothelial cells leads to genome-wide changes in gene expression and DNA methylation, regulating endothelial proliferation and inflammation, as well as mitochondrial deregulation to promote cellular senescence. Hence, ZONAB supports endothelial homeostasis and may play a role in vascular health.</jats:p>
-
Journal articleLundby A, Van Eyk JE, Mayr M, et al., 2026,
Consensus statement on mass spectrometry-based proteomic analysis of cardiac tissue.
, Nat Cardiovasc ResMass 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.
-
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: 11Preclinical 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.
-
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.
-
Journal articleBarallobre-Barreiro J, Mayr M, 2026,
Proteomic insights into bi-atrial remodelling in persistent atrial fibrillation.
, Cardiovasc Res -
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
-
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
-
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.
-
Journal articleSchmidt LE, Burnap SA, Singh B, et al., 2026,
Integrative Proteomic and Lipidomic Analysis of Patients With Acute Myocardial Infarction Treated With PCSK9 Antibodies and Statins.
, Circ Genom Precis Med, Vol: 19BACKGROUND: PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition is a potent cholesterol-lowering strategy. This study examined the effects of PCSK9 monoclonal antibodies (mAbs) and high-intensity statins beyond low-density lipoprotein cholesterol reduction, which are not fully defined, particularly in patients with acute myocardial infarction (MI). METHODS: Proteomic and lipidomic analyses were conducted on plasma from 265 patients with acute MI from the PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction) randomized, placebo-controlled PCSK9 mAb trial and 34 patients without MI with hyperlipidemia from the Vienna Lipid Clinic registry, also receiving PCSK9 mAbs. RESULTS: Discovery proteomics revealed changes in apolipoproteins and increased PCOLCE (procollagen C-endopeptidase enhancer 1) levels in both the PCSK9 mAb and placebo groups after MI. UK Biobank data confirmed PCOLCE and PCSK9 upregulation as associated with statin use. Hepatoma cell experiments demonstrated a dose-dependent PCOLCE induction on statin treatment. Compared with placebo (statins only), PCSK9 mAb therapy resulted in greater reductions in APOB (apolipoprotein B), APOE (apolipoprotein E), APOC2 (apolipoprotein C2), and APOC3 (apolipoprotein C3), as shown by targeted proteomics. Mediation analysis indicated that these changes were largely explained by low-density lipoprotein cholesterol lowering. Lipidomics identified more pronounced reductions in cholesteryl esters, ceramides, sphingomyelins, phosphatidylcholines, triglycerides, and diglycerides in PCSK9 mAb-treated patients with MI. Results were largely consistent in patients without MI. However, levels of LPA (apolipoprotein[a]), the characteristic protein component of lipoprotein(a), remained unchanged in PCSK9 mAb-treated patients with MI, since a rise of LPA was observed in the placebo group post-MI. CONCLUSIONS: Most apolipoprotein changes after PCSK9 m
-
Journal articleHarbaum L, Klose H, Lund J, et al., 2026,
Metabolomic signature of right ventricular-pulmonary arterial coupling differentiates hemodynamic response to imatinib therapy in pulmonary arterial hypertension.
, J Heart Lung Transplant, Vol: 45, Pages: 647-656BACKGROUND: Right ventricular (RV) dysfunction is the leading cause of mortality in pulmonary arterial hypertension (PAH). Although RV metabolic remodeling in chronic pressure overload is recognized, the circulating metabolic signatures of RV-pulmonary arterial (PA) coupling and their clinical relevance remain poorly defined. METHODS: We first integrated pressure-volume-derived RV/PA metrics with untargeted plasma metabolomics in 33 PAH patients, using both network-based and single-metabolite analyses. Findings were replicated in 14 patients using echocardiographic surrogates. In 16 participants from the phase 2 PIPAH trial of imatinib, we examined longitudinal metabolite changes in relation to hemodynamic responses obtained from implanted devices. RESULTS: The end-systolic to arterial elastance ratio (Ees/Ea), a load-independent measure of RV contractility and RV-PA coupling, emerged as a central node in the metabolic network, while metrics related to afterload and RV stiffness were more peripherally located. In individual metabolite analyses, 9 metabolites were significantly associated with Ees/Ea and its echocardiographic surrogate, independent of potential confounders, including kidney and liver function. Pathway enrichment analysis confirmed a predominance of fatty acid metabolism, particularly acylcarnitines. In the PIPAH study cohort, individual-level analyses showed that reductions in acylcarnitine levels at 4 and 24 weeks of imatinib therapy discriminated patients with improved cardiac output (area under the curves 0.89 and 0.84). CONCLUSIONS: We identify a distinct circulating metabolomic signature, enriched in fatty acid metabolites, associated with RV-PA coupling in PAH. These metabolites may inform on the risk and trajectory of RV maladaptation during treatment and guide therapeutic decisions to optimize the benefit-harm ratio.
-
Journal articleFuenderich MT, Yogeswaran A, Janetzko P, et al., 2026,
PVRI-GoDeep-A Global Meta-Registry at the Crossroads of Heart and Lung.
, Compr Physiol, Vol: 16Pulmonary hypertension (PH) is a complex disease characterized by increased pressure in the pulmonary arteries. It encompasses a heterogeneous group of entities that increase right heart afterload and often lead to right heart failure and premature death. Advancing diagnosis, risk stratification, and treatment across the diverse PH spectrum requires large, high-quality, longitudinal datasets that exceed the scope of individual national or regional registries. To address this need, PVRI GoDeep was founded under the umbrella of the Pulmonary Vascular Research Institute (PVRI). This global meta registry harmonizes and integrates anonymized patient-level data from existing PH registries at expert centers worldwide. PVRI GoDeep enables the reuse of locally collected real-world data by mapping heterogeneous datasets to a predefined data dictionary, thorough quality checks, and regular updates. This approach supports phenotyping across all PH groups, enables international comparisons, and allows in-depth analysis of rare subtypes, disease progression, treatment responses, and survival rates. Importantly, GoDeep makes clinically relevant research possible that cannot be conducted at the level of a single center, such as validating risk-stratification tools across PH subgroups, evaluating off-label therapies, and investigating newly recognized entities, such as mild PH. By January 2026, data from more than 45,000 individuals worldwide were integrated into GoDeep, making it one of the largest and most diverse PH registries. Offering a scalable, governed, and disease-independent framework for harmonized real-world evidence generation, PVRI GoDeep is a powerful platform to deepen the understanding of PH and support the development of clinical guidelines for the diagnosis and treatment of PH.
-
Journal articleDelgado-SanMartin JA, Keles M, Errington N, et al., 2026,
Assessing the feasibility of using smartphone data to identify risk of idiopathic pulmonary arterial hypertension
, npj Cardiovascular Health, Vol: 3, ISSN: 2948-2836Idiopathic pulmonary arterial hypertension (IPAH) is a progressive, life-limiting condition often diagnosed late due to non-specific symptoms and requirement of invasive right heart catheterisation. This pilot study explores the feasibility of using real-world physical activity data from wearable devices and a smartphone app (My Heart Counts) to aid earlier detection. We analysed up to eight years of retrospective data from 109 UK participants, including patients with IPAH, disease controls, and healthy individuals. A classifier trained on pre-diagnostic activity and heart rate, distinguished individuals with IPAH from healthy and disease controls with an ROC AUC of 0.87, improving to 0.94 with in-app questionnaire input. Validation in a matched US cohort yielded an ROC AUC of 0.74. Wearable-derived metrics correlated with clinical 6MWD supporting their potential to complement traditional risk assessment. These pilot findings suggest that digital health tools may support earlier detection and remote monitoring of IPAH warranting larger scale studies.
-
Journal articleRajakulasingam R, Alaour B, McGrath S, et al., 2026,
Cardiac myosin-binding protein C in ST-elevation myocardial infarction
, European Heart Journal: Acute Cardiovascular Care, ISSN: 2048-8726AimsCardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, rising and falling more rapidly than cardiac troponins in myocardial infarction (MI), potentially enabling earlier diagnosis. Its performance has not been assessed in reperfused acute ST-segment elevation myocardial infarction (STEMI), against gold-standard biochemical (high-sensitivity cardiac troponin I, hs-cTnI) or imaging (cardiovascular magnetic resonance, CMR) biomarkers. This study tested the hypotheses that: i) cMyC correlates with acute and final MI size by late gadolinium enhancement (LGE) CMR and ii) cMyC is related to the presence of acute microvascular obstruction (MVO) by CMR.Methods and resultsBlood samples were obtained at 6 ± 2 hourly intervals for 24 hours (hrs) for measurement of hs-cTnI and cMyC concentrations in patients with reperfused acute STEMI. Patients underwent 3T LGE-CMR at ∼3–5 days (n = 69) and ∼4 months (n = 65) after reperfusion. Acute cMyC at all timepoints significantly correlated with acute and final MI size on LGE-CMR, most strongly at 6-hrs post reperfusion (r = 0.7, P < 0.001). cMyC at 6-, 12-, 18− and 24-hrs demonstrated significant discriminatory power in identifying patients with acute MVO, with the 6-hr level having the highest discriminative power. Hs-cTnI correlated more strongly with acute and final MI size compared with cMyC and had significantly higher discriminatory ability in identifying MVO at 12−, 18− and 24-hrs.ConclusioncMyC is a quantitative biochemical biomarker of myocardial injury in reperfused STEMI. Further studies, using optimised high-sensitivity assays, are warranted to evaluate its potential as a novel biomarker after acute MI.
-
Journal articleFicany A, Del Alamo M, Bernabeu C, et al., 2026,
Correction: Ficany et al. Epistaxis Prevention, Treatment, and Future Perspectives for Hereditary Hemorrhagic Telangiectasia. J. Clin. Med. 2025, 14, 7724.
, J Clin Med, Vol: 15, ISSN: 2077-0383In the original publication [...].
-
Journal articleKelshiker MA, Chhatwal K, Bachtiger P, et al., 2026,
Safety and effectiveness of remote monitoring and prioritization of patients awaiting transcatheter aortic valve implantation: a propensity-matched prospective observational cohort study.
, Eur Heart J Digit Health, Vol: 7AIMS: Health systems face increasing waiting times for transcatheter aortic valve implantation (TAVI), incurring excess deaths and morbidity. To determine whether remote patient monitoring (RPM) using connected technologies can mitigate these risks by prioritizing patients awaiting TAVI, we aimed to measure the clinical safety and effectiveness of an RPM-based prioritization programme. METHODS AND RESULTS: Prospective observational cohort study of all patients awaiting TAVI at Imperial College Healthcare NHS Trust, London, UK, between 24th April 2023 and 15th November 2023. An RPM pathway was implemented for all patients accepted for TAVI. These patients responded to a weekly symptom questionnaire via web, smartphone RPM platform or telephone monitoring; with rule-based clinical escalation. The primary endpoint was the rate of adverse events (defined as emergency department presentation, unplanned hospitalization, or death), compared with a propensity score-matched (PSM) historical control group. Secondary endpoints included pathway performance characteristics for detection of deterioration. 200 patients met inclusion criteria. Despite growth of the waiting list, responsible for longer waiting times experienced by the RPM group [median 104 days (IQR 61.00-176.00) vs. 75 days (IQR 38.75-118.00)], there was no difference in rates of adverse events between RPM-patients and historical controls (Log rank P = 0.9). The RPM pathway had high sensitivity for prediction of waiting list death (100%). Patients deemed at high-risk of deterioration experienced shorter waiting times to treatment. CONCLUSION: RPM for patients awaiting TAVI is feasible and may mitigate the adverse effects of longer waiting times through accurate detection of deterioration and by informing prioritization decisions.
-
Journal articleKeles M, Wilkins MR, Lawrie A, 2026,
A blood biomarker to specifically identify idiopathic pulmonary arterial hypertension.
, Nat Cardiovasc Res, Vol: 5, Pages: 178-180 -
Journal articleSakkers TR, Mili E, Winter H, et al., 2026,
Atherosclerotic Fibrous Plaques in Women Present ECM Remodeling Linked to TGF-β.
, Circ Res, Vol: 138BACKGROUND: Sex and atherosclerotic plaque histology are intertwined, with fibrous plaques being more prevalent in women. Plaque erosion, a significant contributor to acute coronary syndromes, is linked to fibrous plaques and is more prevalent in women than men. We hypothesize that the molecular drivers of histologically determined fibrous plaques differ between men and women. METHODS: Human end-stage atherosclerotic plaques were isolated from carotid endarterectomy patients included in the Athero-Express Biobank. Fibrous plaques were histologically assessed, linked to clinical characteristics, and processed for protein, bulk RNA, single-cell RNA, and DNA methylation data. We leveraged sex-differential gene expression and deconvolution analyses to uncover sex-biased molecular and cellular mechanisms. Spatial transcriptomics localized gene expression patterns in plaques. Furthermore, we studied the female-biased processes in human plaque endothelial cells and vascular smooth muscle cells stimulated with TGF-β (transforming growth factor-β), with or without SMAD3 (SMAD family member 3) inhibition. RESULTS: Of 1889 atherosclerotic plaques (1309 male and 580 female), fibrous lesions were observed in 50% of female and 31% of male patients. Compared with patients with atheromatous plaques (n=494), women with fibrous plaques exhibited a high prevalence of smoking, while men with fibrous plaques presented more often with diabetes. Female fibrous plaques were characterized by smooth muscle cell-driven ECM (extracellular matrix) remodeling, TGF-β response, and endothelial-to-mesenchymal transition, localized to the fibrous cap. Conversely, male plaques were linked to macrophage-mediated inflammation proximal to the core, dependent on diabetes. Finally, we experimentally confirmed these female-biased mechanisms, showing that TGF-β induced endothelial-to-mesenchymal transition in endothelial cells and ECM remodeling in vascular smooth muscle cells, both part
-
Journal articleDucker CB, Preece MV, Pericleous C, et al., 2026,
Revisiting antiphospholipid syndrome: A thrombo-inflammatory disorder beyond clotting.
, Blood RevThe dysregulation of protective immunothrombosis is termed thrombo-inflammation. Antiphospholipid syndrome (APS) is an antibody mediated autoimmune, inflammatory and prothrombotic disease. APS is an archetypal disease for thrombo-inflammation, in which a proinflammatory/prothrombotic state is caused by antiphospholipid antibodies (aPL). These antibodies directly or indirectly exert effects on monocytes and neutrophils, as well as platelets and endothelium, through binding of phospholipid binding proteins. In addition, aPL are linked with activation of coagulation and complement, leading to thrombosis. Although APS is an autoimmune antibody-mediated prothrombotic disease, its main treatment strategy at present is anticoagulation. Anticoagulation does not modulate endothelial cells or inflammation. This could explain the high risk of recurrent thrombosis, despite patients being on adequate anticoagulation. This review examines endothelial dysfunction and thrombo-inflammation in thrombotic APS as understanding the role of thrombo-inflammation in the pathogenesis of APS may help to develop new treatments or repurpose existing treatments.
-
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 ImagingAn 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.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.