A5019555799- Pulmonary Hypertension Research and Treatments
- Proteoglycans and glycosaminoglycans research
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Congenital Diaphragmatic Hernia Studies
- Congenital Heart Disease Studies
- Congenital heart defects research
- Neonatal Respiratory Health Research
- Superconducting Materials and Applications
- Cardiovascular Issues in Pregnancy
- Advanced X-ray Imaging Techniques
- Advanced X-ray and CT Imaging
- Medical Imaging and Pathology Studies
- Connective tissue disorders research
- Transplantation: Methods and Outcomes
- Cardiac Valve Diseases and Treatments
- Atherosclerosis and Cardiovascular Diseases
- Nerve injury and regeneration
- Neuroendocrine Tumor Research Advances
- Advanced Electron Microscopy Techniques and Applications
- Neuroblastoma Research and Treatments
- Biotin and Related Studies
- Mechanical Circulatory Support Devices
- Aortic Disease and Treatment Approaches
- Angiogenesis and VEGF in Cancer
Lund University
2016-2025
Skåne University Hospital
2017-2025
Wallenberg Wood Science Center
2020
Karolinska Institutet
2000-2017
Great Ormond Street Hospital
2015-2017
University College London
2015-2017
Karolinska University Hospital
1999-2012
Virginia Mason Medical Center
2008
Benaroya Research Institute
2008
University of Oulu
2008
Heparan sulfate (HS) has been proposed to be antiatherogenic through inhibition of lipoprotein retention, inflammation, and smooth muscle cell proliferation. Perlecan is the predominant HS proteoglycan in artery wall. Here, we investigated role perlecan chains using apoE null (ApoE0) mice that were cross-bred with expressing HS-deficient (Hspg2(Delta3/Delta3)). Morphometry cross-sections from aortic roots en face preparations whole aortas revealed a significant decrease lesion formation...
Smooth muscle cell (SMC) proliferation is a critical process in vascular disease. Heparan sulfate (HS) proteoglycans inhibit SMC growth, but the role of endogenous counterparts vessel wall control function not known detail. Perlecan major HS basement membranes and extracellular matrix (ECM). In this study, transgenic mice with HS-deficient perlecan were analyzed respect to phenotype intimal lesion formation. Furthermore, cultures established characterized morphology, immunocytochemical...
This study aimed to explore the value of synchrotron-based phase-contrast microcomputed tomography (micro-CT) in pulmonary vascular pathobiology. The microanatomy lung is complex with intricate branching patterns. Tissue sections are therefore difficult interpret. Recruited intrapulmonary bronchopulmonary anastomoses (IBAs) have been described several forms hypertension, including alveolar capillary dysplasia misaligned veins (ACD/MPV). Here, we examine paraffin-embedded tissue using this...
The physiological roles of the metalloprotease-proteoglycan ADAMTS7, a drug target in atherosclerosis and vascular restenosis, its homolog ADAMTS12, are undefined cardiovascular system. objective present work was to investigate their mice with genetic inactivation both proteases relation resulting valve defects, define proteolytic activities matrisome. Here, we demonstrate that Adamts7 Adamts12 co-expressed heart valves each buffers other by compensatory upregulation. Leaflets -/-;Adamts12...
In pulmonary arterial hypertension, plexiform lesions are associated with severe obstruction and right ventricular failure. Exploring their structure position is crucial for understanding the interplay between hemodynamics vascular remodeling. The aim of this research was to use synchrotron-based phase-contrast micro-CT study three-dimensional lesions. Archived paraffin-embedded tissue samples from 14 patients hypertension (13 idiopathic, 1 known BMPR2-mutation) were imaged. Clinical data...
Inflammatory responses of large vein endothelium are importance in pathological processes such as venous thrombosis, chronic congestion, and graft atherosclerosis. However, the inflammatory properties unclear.In this study, we used several microscopy techniques to investigate vivo. We show that mouse inferior vena cava (IVC) possesses powerful distinct from less reactive aortic virtually identical endothelial postcapillary venules. stimulation with tumor necrosis factor-alpha induced strong...
Heparan sulfate (HS) has been proposed to be antiatherogenic through inhibition of lipoprotein retention, inflammation, and smooth muscle cell proliferation. Perlecan is the predominant HS proteoglycan in artery wall. Here, we investigated role perlecan chains using apoE null (ApoE0) mice that were cross-bred with expressing HS-deficient ( Hspg2 Δ3/Δ3 ). Morphometry cross-sections from aortic roots en face preparations whole aortas revealed a significant decrease lesion formation ApoE0/ at...
Pulmonary arterial hypertension (PAH) is a lethal condition for which there no effective curative pharmacotherapy. PAH characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican chondroitin sulfate proteoglycan in the extracellular matrix that accumulates following injury promotes smooth-muscle cell proliferation systemic arteries. Here, we investigated whether versican may play similar role PAH. Paraffin-embedded lung sections from...
In atherogenesis and in response to vessel injury, arterial smooth muscle cells (SMCs) are activated from a quiescent, differentiated state into an actively proliferating synthetic phenotype which migrate the intima where participate formation of fibrous plaque or intimal hyperplasia. The mechanisms involved control SMC function not clear no preventive therapy against activation is available. Interactions between SMCs extracellular matrix have been shown influence structure through...
Excessive vascular cell proliferation is an important component of pulmonary hypertension (PH). Perlecan the major heparan sulfate (HS) proteoglycan in extracellular matrix. It binds growth factors, including FGF2, and either restricts or promotes proliferation. In this study, we have explored effects perlecan HS deficiency on development hypoxia-induced PH. normoxia, Hspg2Δ3/Δ3 mice, deficient HS, had reduced pericytes muscularization intra-acinar vessels. Pulmonary angiography revealed a...
Abstract Expansion of extracellular matrix occurs in all stages pulmonary angiopathy associated with arterial hypertension (PAH). In systemic arteries, dysregulation and accumulation the large chondroitin‐sulfate proteoglycan aggrecan is swelling disruption vessel wall homeostasis. Whether present its potential roles PAH, has not been thoroughly investigated. Here, lung tissue from 11 patients idiopathic PAH was imaged using synchrotron radiation phase‐contrast microcomputed tomography...
In immunocytochemical studies, the CSF from Parkinson disease (PD) patients and Alzheimer (AD) were investigated for presence of neuron specific antibodies using dopaminergic cholinergic neuronal cultures embryonic rat brain, respectively. Dopamine containing cell bodies labelled by Parkinsonian CSF-IgG, while neurons, identified with a-NGF-receptor antibodies, recognized AD-patients. The PD-patients was after autologous adrenal transplantation. removed 7d, 5 months 1 year operation. When...
The pathophysiology of congenital diaphragmatic hernia (CDH) is constituted by pulmonary hypoplasia and hypertension (PH). We previously reported successful treatment with imatinib a patient CDH. This study examines the effect antenatal administration on vasculature in rat model Pregnant rats were given nitrofen to induce Controls olive oil. Half CDH fetuses half controls treated antenatally E17-E21, rendering four groups: Control, Control+Imatinib, CDH, CDH+Imatinib. Lung sections obtained...
Two inherent challenges in the mechanistic interpretation of protease-deficient phenotypes are defining specific substrate cleavages whose reduction generates and determining whether result from loss function, accumulation, or a function(s) embodied fragments. Hence, recapitulation phenotype by cleavage-resistant would stringently validate importance proteolytic event clarify underlying mechanisms. Versican is large proteoglycan required for development circulatory system proper limb...
Changes in the extracellular matrix of pulmonary arteries (PAs) are a key aspect vascular remodeling hypertension (PH). Yet, our understanding alterations affecting proteoglycan (PG) family remains limited. We sought to investigate expression and spatial distribution major PGs PAs from healthy individuals various PH groups (chronic obstructive disease: PH-COPD, fibrosis: PH-PF, idiopathic: IPAH). PG regulation, deposition, synthesis were notably heightened IPAH, followed by with minor...
A questionnaire measuring food frequency was validated against 7-day records of intake in a group 30 children, 2-16 years age. Special emphasis given to the ability estimate foods particular interest diabetes mellitus. Fifteen children had insulin-dependent diabetes; 15 were healthy. Comparison two methods regarding with high content sucrose, protein, fat, fibres, nitrite or vitamin C showed correlation 0.52-0.76. The some staple often overestimated by questionnaire, while meat, sausage and...
The umbilical artery lumen closes rapidly at birth, preventing neonatal blood loss, whereas the vein remains patent longer. Here, analysis of cords from humans and other mammals identified differential arterial-venous proteoglycan dynamics as a determinant these contrasting vascular responses. artery, but not vein, has an inner layer enriched in hydrated aggrecan, external to which lie contraction-primed smooth muscle cells (SMC). At SMC contraction drives buckling centripetal displacement...
Abstract Smooth muscle cell migration, proliferation, and deposition of extracellular matrix are key events in atherogenesis restenosis development. To explore the mechanisms that regulate smooth function, we have investigated whether perlecan, a basement membrane heparan sulfate proteoglycan, modulates interaction between cells other components. A combined substrate fibronectin perlecan showed reduced adhesion rat aortic by 70–90% comparison to alone. In contrast, did not interfere with...
Abstract Activation of the kynurenine pathway (KP) has been reported in patients with pulmonary arterial hypertension (PAH) undergoing PAH therapy. We aimed to determine KP-metabolism treatment-naïve patients, investigate its prognostic values, evaluate effect therapy on KP-metabolites and identify cytokines responsible for altered KP-metabolism. KP-metabolite levels were determined plasma from (median follow-up 42 months) rats monocrotaline- Sugen/hypoxia-induced PH. Blood sampling was...
Abstract In children with single ventricle physiology, increased pulmonary vascular resistance may impede surgical progression or result in failing physiology. The use of vasodilators has been suggested as a potential therapy. However, knowledge on indication, dosage, and effect is limited. A retrospective case notes review all ( n = 36) treated by the UK Pulmonary Hypertension Service for Children 2004–2017. Therapy was initiated Stage 1 12), Glenn 8), TCPC 16). Treatment indications were...
The use of pulmonary vasodilator therapy in children born preterm is largely unknown. Our aim was to map prescription patterns with bronchopulmonary dysplasia Sweden.This a descriptive national registry-based study <7 years who had been prescribed during 2007-2017, were and classified as having dysplasia. Information on prescriptions, patient characteristics comorbidities retrieved from the Swedish Prescribed Drug Register linked other registers.The included 74 children, 54 (73%) at 22-27...
Abstract High-resolution x-ray tomography is a common technique for biomedical research using synchrotron sources. With advancements in laboratory sources, an increasing number of experiments can be performed the lab. In this paper, design, implementation, and verification setup nano-computed presented nano-focus source high geometric magnification not requiring any optical elements. Comparing scintillator-based detector to photon counting shows clear benefit detectors these applications,...