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Journal articleSharma T, Fall T, Sayols-Baixeras S, et al., 2026,
Linking Lipidomics to Vulnerable Coronary Plaques: A PROSPECT II Substudy.
, Arterioscler Thromb Vasc Biol, Vol: 46BACKGROUND: Lipidomics, the comprehensive profiling of circulating lipid species, has emerged as a powerful tool to investigate metabolic alterations underlying coronary atherosclerosis. Understanding the mechanisms driving high-risk vulnerable plaque formation and progression to myocardial infarction remains a key therapeutic priority. This study investigates associations between circulating lipid metabolites and imaging-defined features of vulnerable coronary plaque. METHODS: Following revascularization, patients with myocardial infarction underwent 3-vessel coronary artery imaging with near-infrared spectroscopy and intravascular ultrasound to assess nonflow-limiting plaques for lipid core burden index and plaque burden. Multivariable models evaluated associations between 424 lipid metabolites in plasma, quantified by mass spectrometry, pan-coronary lipid, pan-coronary plaque burden, and high-risk vulnerable plaque measures (maximum lipid core burden index within any 4-mm segment across the entire lesion ≥324.7 and/or plaque burden ≥70%) in 877 patients. Findings were validated in the SCAPIS study (Swedish Cardiopulmonary Bioimage Study) using coronary computed tomography angiography-based measures of coronary artery calcium score and segment involvement score. RESULTS: We identified 156 significant associations (P<0.05) between lipid metabolites and coronary plaque characteristics across 39 metabolic pathways. Sphingomyelins were inversely associated with all plaque metrics, and 1-palmitoyl-2-oleoyl-GPE (glycero-3-phosphoethanolamine; 16:0/18:1), a phosphatidylethanolamine, was positively associated with all plaque metrics. After correcting for multiple testing, 27 lipid species across 7 pathways remained significant (q<0.05). The majority were linked to pan-coronary lipid burden, with the strongest inverse association observed for sphingomyelin d18:1/22:1, d18:2/22:0, and d16:1/24:1. Similar inverse patterns were seen for select dihydrosphingomyelin
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Journal articleSchmiedmayer P, Johnson A, Schuetz N, et al., 2026,
Design and rationale of the my heart counts cardiovascular health study: a large-scale, fully digital biobank, and randomized trial of large language model-driven coaching of physical activity.
, Am J Prev Cardiol, Vol: 28BACKGROUND: Cardiovascular disease remains the leading cause of global morbidity and mortality. The original My Heart Counts smartphone application demonstrated the feasibility of large-scale, fully digital recruitment and trial conduct, but was limited by platform exclusivity and the need for human experts to create text-based behavioral interventions. METHODS: The next-generation My Heart Counts smartphone application is a prospective, observational cohort study with an embedded randomized crossover trial, evaluating personalized text-based coaching prompts, available in both English and Spanish. All study and trial operations will be conducted via the My Heart Counts smartphone application, re-designed using the open-source Stanford Spezi framework to support iOS, with a planned Android release in 2027. The target enrollment is N = 15,000 adults across the United States and United Kingdom. The study establishes a comprehensive digital biobank by synthesizing passive mobile health data (steps, flights climbed, heart rate, sleep, workouts), raw sensor data (e.g., accelerometry), longitudinal clinical surveys, active tasks (6-minute walk test and 12-minute Cooper run test), electrocardiograms (ECG), and electronic health record (EHR) data integrated via HL7 FHIR protocols. The embedded trial evaluates the effect of text-based coaching prompts generated by a large language model (LLM) grounded in the Transtheoretical Model of Change on daily physical activity, as compared to generic prompts. PLANNED ANALYSIS: The primary endpoint of the randomized crossover trial is change in daily step count between LLM-driven and generic text-based intervention arms, analyzed using mixed-effects models. Secondary endpoints include change in mean active minutes and calorie burn over each intervention week. Other exploratory analyses include the changes in submaximal (6-minute walk test) and maximal (Cooper 12-minute run test) cardiorespiratory fitness, changes to sensor-derived biom
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Journal articleYin S, Mayr U, Barallobre-Barreiro J, et al., 2026,
Aortic Stenosis Hyalectan Remodeling Revealed by Proteomics and Glycoproteomics.
, Arterioscler Thromb Vasc BiolBACKGROUND: Calcific aortic valve (AV) disease (CAVD) is recognized as an active pathological process involving extracellular matrix remodeling. This study investigates extracellular matrix remodeling through proteomic analysis and a novel mouse model of aortic stenosis. METHODS: Proteomic and glycoproteomic analyses were conducted on AV leaflets from heart transplant donors (n=29) and patients with CAVD (n=17). Each CAVD sample was subdivided into noncalcified and calcified regions. To investigate the functional impact of extracellular matrix remodeling on aortic stenosis, we crossed apolipoprotein E-deficient mice (ApoE-/-) with mice lacking the catalytic domain of ADAMTS5 (Adamts5Δcat) to generate a mouse model combining hyalectan accumulation with hypercholesterolemia. RESULTS: Proteomic and glycoproteomic analyses revealed hyalectan accumulation in CAVD compared with control valves. Versican predominated in noncalcified regions, while aggrecan was enriched in calcified regions. The shift in hyalectan composition correlated with changes in AV pressure gradient, elevated osteoblast-like cell markers, and inflammatory proteins, most notably pentraxin 3. Both versican and aggrecan are characterized by their ability to bind hyaluronan and serve as substrates of ADAMTS5. In Adamts5Δcat/ApoE-/- mice, hyalectan accumulation was associated with narrowed aortic cusp separation and increased post-AV velocity. Proteomic analysis of AVs from Adamts5Δcat/ApoE-/- mice revealed elevated versican, aggrecan, and pentraxin 3, recapitulating key features of human CAVD. Single-cell RNA sequencing and in vitro experiments linked versican to activated valve interstitial cells, while aggrecan colocalized with calcification markers in osteoblast-like cells. Pentraxin 3 was bound to hyaluronan and accumulated in calcified AVs. ADAMTS5 deficiency was sufficient to cause intact versican accumulation and promote valve interstitial cell differentiation, as evidenced by inc
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Journal articleYogeswaran A, Fünderich M, Wendlandt K, et al., 2026,
Angiotensin Converting Enzyme Inhibition and Mortality in Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
, Pulmonary Circulation, Vol: 16, ISSN: 2045-8932In 567 PH-COPD patients from the PVRI GoDeep Meta-Registry, ACE inhibitor use was associated with improved survival only in severe PH (PVR > 5 WU), supporting prospective trials targeting this high-risk subgroup.
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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 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 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 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 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 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: 15Regulation 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.
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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 articleKhawaja SA, Hanna L, Singh A, et al., 2026,
A randomized trial of carbon-dioxide flushing to reduce vascular brain injury in patients undergoing TAVI.
, EuroInterventionBACKGROUND: Stroke remains a significant concern in patients undergoing Transcatheter Aortic Valve Implantation (TAVI). Despite advances in TAVI technology and techniques, rates have remained unchanged, with trials of Cerebral embolic protection devices (CEPD) failing to reduce rates. The concept of air emboli has never been previously investigated in TAVI procedures. We hypothesize that gaseous emboli could play a significant role in TAVI and that carbon dioxide (COâ) flushing of the TAVI valves could reduce the incidence of new neurological lesions post-TAVI. AIMS: To demonstrate the neuroprotective benefits of COâ flushing in TAVI. METHODS: INTERCEPTavi is a pilot single centre, blinded, randomized controlled trial that studied the effects of flushing TAVI valves with COâ versus conventional saline on neurological outcomes post TAVI assessed using MRI and transcranial doppler(TCD). Patients with aortic stenosis were randomised after access was obtained. Peri-procedure TCD assessed solid and gas emboli to the brain. Post-procedure, patients underwent brain MRI to detect lesions. Here we report the primary outcome of feasibility, as well as the secondary MRI and mechanistic TCD data. RESULTS: 60 patients were recruited and randomised 1:1 to COâ and saline flushing (TAVI-COâ) versus saline flushing only (TAVI-S). COâ flushing significantly reduced the average number of lesions per patient (TAVI-COâ 4 lesions/patient vs TAVI-S 8.5 lesions/patient; P=0.031). The total infarct area was numerically lower in the COâ group (40.32 mm² vs 93.20 mm²), although this did not reach statistical significance (p=0.111). Similarly, Transcranial Doppler (TCD) showed fewer micro-embolic signals in the COâ arm, primarily due to a reduction in gaseous emboli, but this difference was not statistically significant (p=0.5). CONCLUSIONS: INTERCEPTavi is a pioneering first-in-man randomised trial that demonstrated that COâ
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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 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 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 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.
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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
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