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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 BiolBACKGROUND: 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 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 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.
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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
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Journal articleKeles M, Wilkins MR, Lawrie A, 2026,
A blood biomarker to specifically identify idiopathic pulmonary arterial hypertension.
, Nat Cardiovasc Res -
Journal articleDe Silva R, 2026,
Cardiac myosin-binding protein C in ST-elevation myocardial Infarction
, European Heart Journal: Acute Cardiovascular Care, ISSN: 2048-8726Background and Aims: Cardiac 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: Blood 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.Results: 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 to cMyC and had significantly higher discriminatory ability in identifying MVO at 12-, 18- and 24-hrs.Conclusions: cMyC 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.
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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.
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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 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.
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Journal articleOshima A, Serruys PW, Garg S, et al., 2026,
Adjunctive pharmacological strategies for residual risk reduction after myocardial revascularisation.
, EuroIntervention, Vol: 22, Pages: 202-223Pharmacological treatment remains vital in the effective management of atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein (LDL) cholesterol-lowering therapies, such as statins, have consistently demonstrated robust efficacy in the primary and secondary prevention of cardiovascular events. The introduction of ezetimibe, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 inhibitors have further strengthened the effectiveness of LDL cholesterol management, particularly in patients who are statin intolerant or who remain at high risk despite maximal tolerated statin therapy. In addition to managing LDL cholesterol, addressing residual lipid risk by targeting elevated triglyceride and lipoprotein(a) levels and low high-density lipoprotein cholesterol levels has emerged as a potentially important therapeutic consideration, as these are increasingly recognised as independent cardiovascular risk factors. Concurrently, inflammation is increasingly acknowledged as a significant contributor to atherogenesis and subsequent cardiovascular events. Clinical trials examining anti-inflammatory therapies, such as colchicine and interleukin-1β inhibitors (e.g., canakinumab), have demonstrated beneficial effects in reducing cardiovascular events independent of lipid modification. This narrative review provides an updated overview targeted specifically at physicians performing coronary artery bypass grafting or percutaneous coronary intervention. It summarises current evidence regarding established lipid-lowering therapies, emerging therapeutic approaches to address residual lipid risk, and the evolving role of anti-inflammatory interventions in the comprehensive management of ASCVD.
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Journal articleSchmidt LE, Burnap SA, Singh B, et al., 2026,
Integrative Proteomic and Lipidomic Analysis of Post-Myocardial Infarction Patients Treated With PCSK9 Antibodies and Statins.
, Circ Genom Precis MedBACKGROUND: 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: Combined proteomics and lipidomics analyses was 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, APOE, APO C2, and APO 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 mAb therapy after MI were mediated by low-density lipoprotein chole
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Journal articleSingh B, Karpov OA, Mayr M, 2026,
Clinical proteomics in cardiovascular medicine: Current capabilities, limitations, and future directions.
, Atherosclerosis, Vol: 413BACKGROUND AND AIMS: Commercial high-throughput proteomics platforms, such as Olink and SomaLogic, enable large-scale epidemiological studies with integrated multi-omics measurements. While these proteomics approaches have been widely applied in biobanks, issues of data quality remain underappreciated. In this review, we discuss these limitations and outline a way forward for realizing the clinical translation of proteomics as a comprehensive 'liquid health check'. METHODS: We reviewed the recent literature for artificial intelligence (AI) and multi-omics, particularly proteomics in atherosclerotic cardiovascular disease (ASCVD). RESULTS: AI-driven multi-omics analyses have the potential to advance our understanding of multifactorial causes of ASCVD, including aging. Emerging concepts such as "ageotypes" suggest the potential for personalized intervention to slow aging processes. Commercial proteomics platforms have accelerated biomarker discovery in ASCVD, but challenges remain in clinical translation. Limited correlation between Olink and SomaLogic necessitates orthogonal validation of findings. Platform-specific issues, such as epitope effects and cross-reactivity, can yield divergent protein quantitative trait loci for the same protein, complicating causal inference. While tissue proteomics provides complementary insights to plasma proteomics, reliance on autopsy samples raises concerns about protein degradation and measurement reliability. Increasingly, single-cell and spatial proteomics are being explored to better capture plaque heterogeneity, complementing bulk proteomics in larger cohorts. CONCLUSION: Beyond risk prediction, proteomics offers opportunities to elucidate disease mechanisms and enable drug repurposing. To realize the clinical potential of plasma proteomics, absolute or reliably recalibratable relative quantification will be required to guide patient care. Ultimately, the clinical value of proteomics will be determined by the quality
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Journal articleSimader FA, Rajkumar CA, Foley MJ, et al., 2026,
Association Between Age and PCI Effectiveness in Stable CAD: Secondary Analysis of ORBITA-2.
, J Am Coll Cardiol, Vol: 87, Pages: 253-265BACKGROUND: ORBITA-2 (Objective Randomized Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) was the first randomized placebo-controlled trial to show the efficacy of percutaneous coronary intervention (PCI) in patients with stable angina and single- or multivessel coronary artery disease without background antianginal medication. Whether the effect is consistent across age groups is unknown. OBJECTIVES: The authors sought to evaluate the interaction between age and symptom and stenosis severity, and the efficacy of PCI on the ORBITA-2 primary and secondary endpoints. METHODS: All patients from the primary ORBITA-2 trial contributed data to this post hoc analysis. For daily symptoms, a bayesian longitudinal Markov model was constructed. For treadmill exercise time, stress echocardiography, and questionnaires, a bayesian ordinal proportional odds model was used, including the prerandomization value and treatment arm, which were allowed to interact with age. RESULTS: The mean age was 64 ± 9 years, ranging from 40 to 82 years. There was little relationship between age and symptom and stenosis severity. In older patients, PCI was more effective for symptom relief (OR: 2.03; 95% CrI: 1.67-2.45; Pr > 0.99) than in younger patients (OR: 1.70; 95% CrI: 1.38-2.15; Pr > 0.99; Pr [interaction] = 0.99). In contrast, the effect of PCI on treadmill exercise time was far greater in younger than in older patients (50-year-old: +125 s [95% CrI: 35.8-215.0 s; Pr > 0.99]; 70-year-old: +31.9s [95% CrI: -12.6 to 78.3; Pr = 0.92]; Pr [interaction] = 0.96). CONCLUSIONS: PCI was effective across all ages in reducing angina frequency. Notably, there was limited improvement in treadmill exercise time in the elderly, challenging its role as a primary endpoint in many antianginal trials. These data should inform cardiovascular clinical trial design to ensure applicability across all ages. (Objective Randomized Blinded Investigation With Optimal
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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, ISSN: 0006-4971<jats:p>Management 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 Endothelial Cells (HUVEC) and endothelial colony forming cells (ECFCs) from severe VWD patients, we find that loss of VWF results in increased Angpt-2 expression through the positive feedback loop Angpt-2-TIE2-AKT-FOXO1-Angpt-2. In the gut of VWF-deficient mice, Angpt-2 expression is increased whilst Angpt-1 expression is decreased, suggesting that VWF regulates the Angpt/Tie2 balance in the gut. Moreover, the intestinal vasculature in the jejunum of VWF-deficient mice appears abnormal, with hyper-sprouting and lumen formation defects. The findings reveal VWF-deficient mice as a model to study gut angiodysplasia. We investigate sprouting angiogenesis in vitro using a fibrin bead assay and find increased sprouting in VWF-deficient EC. We develop a 3D-microfluidic model of angiogenesis and find that ECFCs from severe VWD patients exhibit defective remodeling and abnormal lumen formation, reminiscent of the defects in the gut of VWF KO mice. Importantly, inhibition of Angpt-2 reduces sprouting in VWF-deficient HUVEC and normalises vascular remodeling in VWD ECFCs, suggesting that Angpt-2 inhibitors may be effective in VWD patients with GI bleeding and angiodysplasia.</jats:p>
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Journal articleKelly J, Salih M, Patel A, et al., 2026,
Aquaporin-4: A Predictor and Therapeutic Target for Permanent Paraplegia after Endovascular Thoracoabdominal Aortic Aneurysm Repair.
, Eur J Vasc Endovasc SurgOBJECTIVE: Endovascular thoracoabdominal aortic aneurysm (TAAA) repair can impair spinal cord perfusion, leading to paraplegia. The mechanisms driving this devastating complication are poorly understood. This study aimed to interrogate the cerebrospinal fluid (CSF) proteome in patients after TAAA repair to identify biomarkers that herald permanent paraplegia. It also aimed to investigate a potential therapeutic target identified by proteomics using an in vivo model of ischaemic spinal cord injury (iSCI). METHODS: CSF was collected for proteomic analysis from patients before and following TAAA repair. A differentially expressed protein identified in human paraplegic subjects was subsequently interrogated in a rodent model of iSCI. The protein composition of CSF was analysed using tandem mass tag proteomics. Neurological examinations were carried out by a blinded neurologist and T2 weighted magnetic resonance imaging (MRI) was used to measure spinal cord volume/oedema. A rodent model of iSCI was used to investigate a clinically relevant therapeutic target informed by proteomic findings. RESULTS: CSF analysis was taken from 37 patients, all of whom had aneurysm repair using a custom branched/fenestrated device (median age 73.5 years (range 67 - 78); 27 males, ten females; Crawford classification: six type I, 11 type II, 15 type III, three type IV, and two type V). Five patients remained permanently paraplegic and seven recovered from transient paraplegia. CSF of patients who remained paraplegic contained approximately fourfold more aquaporin-4 (AQP4) (41.8 ± 19.2 ng/mL, n = 5) than those who recovered from paraplegia (10.8 ± 1.3 ng/mL, n = 7; p = .01), or did not develop paraplegia (10.8 ± 1.2 ng/mL, n = 25; p = .004). Permanently paraplegic patients had CSF AQP4 levels > 15 ng/mL and this was associated with greater cord oedema on T2 weighted magnetic resonance imaging (1.77 ± 0.19 vs. 1.03 ± 0.36; p = .03). In a rodent model of i
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Journal articleMeena D, Huang J, Smith A, et al., 2026,
Blood pressure, plasma proteins and cardiovascular diseases: a network Mendelian randomisation and observational study
, European Heart Journal, Vol: 47, Pages: 331-342, ISSN: 0195-668XBackground and AimsThe biological pathways leading to elevated blood pressure (BP) and subsequent cardiovascular diseases (CVDs) remain incompletely understood. Investigating the proteomic landscape of BP and its overlap with CVD could provide critical insights into the molecular determinants and pathways involved in BP regulation and its subsequent effect on CVD.MethodsA proteome-wide Mendelian randomization (MR) study was conducted by leveraging genetic instruments from 2007 plasma proteins to assess their causal effects on BP (systolic and diastolic BP). Proteins showing strong associations with BP were further analyzed for potential causal effects on coronary artery disease (CAD) and stroke subtypes. Network MR was performed to estimate the proportion of CVD risk mediated through BP. Bayesian colocalization was applied to determine whether identified associations share common causal variants. Observational associations were examined in UK Biobank participants to assess associations between proteins, BP, and incident CVD events using linear regression and Cox proportional hazard models.ResultsProteome-wide MR identified 242 proteins associated with BP, of which 48 were also linked to CAD or stroke, with four (ACOX1, FGF5, FURIN, MST1) also supported by genetic colocalization analyses (FDR 5% and PP ≥70%). Genetically predicted FURIN and FGF5 were strongly associated with BP and stroke risk, while ACOX1, FGF5, and MST1 exhibited potential causal effects on CAD. Network MR suggested that a substantial proportion of their effect on CAD and stroke (30.5%–77.2%) was mediated through BP regulation. Observational analyses further supported these findings.ConclusionsThis study identifies key plasma proteins with potential causal roles in BP regulation and CVD risk, highlighting BP as a major mediator of their effects on CAD and stroke. These findings provide novel insights into the molecular mechanisms underlying hypertension-related CVD and identify promising p
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Journal articleYogeswaran A, Annis JS, Funderich M, et al., 2026,
Male survival disadvantage in pulmonary hypertension: independent of aetiology, age, disease severity, comorbidities and treatment
, EBIOMEDICINE, Vol: 123, ISSN: 2352-3964 -
Journal articleVon Koch S, Sharma T, Khamis R, et al., 2026,
Long-acting nitrate use before and after revascularization to evaluate angina in chronic coronary syndrome: a case-crossover study from SCAAR
, LANCET REGIONAL HEALTH-EUROPE, Vol: 60, ISSN: 2666-7762 -
Journal articleHada M, Collet C, Storozhenko T, et al., 2026,
Rationale and design of European microcirculatory resistance and absolute flow team: The Euro-CRAFT registry
, AMERICAN HEART JOURNAL, Vol: 291, Pages: 136-143, ISSN: 0002-8703 -
Journal articleSamaranayake CB, Chen Y-C, Fang M, et al., 2026,
GLP-1 agonist, semaglutide use in acute pulmonary embolism recovery: a four-week proof-of-concept study including proteomic profiling.
, Eur Heart J Open, Vol: 6AIMS: Vasorelaxant and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) agonists support their investigation in aiding the recovery of patients with acute pulmonary embolism (PE) at risk of worse outcomes. METHODS: We undertook a four week non-randomized, controlled open-label study examining proteomic changes, markers of vascular inflammation and exploratory imaging endpoints in response to GLP-1 agonist, semaglutide (0.25 mg weekly) added to standard of care anticoagulation in patients with intermediate high-risk PE. RESULTS: 44 plasma proteins were downregulated in response to semaglutide that were significantly enriched for glycoproteins (false discovery rate q < 0.01). Glycopeptide analysis of highly abundant glycoproteins between diagnosis and follow-up demonstrated a reduction in glycopeptide abundance suggesting protein deglycosylation as a possible mechanism of glycoprotein down-regulation. Down-regulated proteins included regulators of metabolic stress and complement pathway intermediates, which were at higher abundance in PE patients at diagnosis compared to age and sex-matched controls without PE (all P < 0.001). Exploratory evaluation of radiological markers of right ventricular dysfunction improved from baseline to follow-up only in patients who received semaglutide (P < 0.01). CONCLUSIONS: These findings suggest merit in wider investigation of immunometabolic changes in the plasma proteome during acute PE recovery and their potential relevance to modulation using GLP-1 agonists. REGISTRATION: The study was registered under clinicaltrials.org (NCT06118203).
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Journal articleHoward LS, Kiely DG, Lawrie A, et al., 2026,
Performance of Guideline-Recommended Approaches to Echocardiographic Investigation for Pulmonary Hypertension: Analysis of the CIPHER Study.
, Pulm Circ, Vol: 16, ISSN: 2045-8932Guidelines recommend different approaches to investigate for pulmonary hypertension (PH) by transthoracic echocardiography (TTE). We used data from the CIPHER study (NCT04193046) to prospectively evaluate TTE detection of PH. Participants newly referred to PH clinics who underwent right heart catheterization (RHC) within 6 weeks and TTE within 60 days of enrolment (blinded central TTE reading) were classified by TTE probability of PH applying (i) the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) TTE algorithm or (ii) right ventricular systolic pressure (RVSP) > 40 mmHg. For calculation of sensitivity and specificity, 'non-assessable' patients (peak tricuspid regurgitation velocity [TRV] missing or ≤ 2.8 m/s with missing data on other echocardiographic signs) and patients with missing RVSP were counted as PH-negative. Performance was measured against RHC-confirmed diagnosis of mean pulmonary artery pressure > 20 mmHg. Of 475 patients included, 345 (73%) had PH. Using the ESC/ERS algorithm, PH probability was high, intermediate, low and non-assessable for 198, 104, 22 and 151 patients and PH prevalence was 98%, 75%, 23%, and 44%, respectively. Seventy-three patients were missing RVSP and 292 had RVSP > 40 mmHg. The two TTE approaches achieved similar results: sensitivity was 79%-77%, specificity was 78%-79%. This prospective study of patients newly referred to PH centres for RHC found similar sensitivity and specificity when using either RVSP > 40 mmHg or the 2015 ESC/ERS TTE algorithm. Among patients who were low-probability or non-assessable by ESC/ERS algorithm, 42% had PH, highlighting the persistent need for additional non-invasive investigative tools.
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