A5053785237- Vascular Tumors and Angiosarcomas
- Vascular Malformations and Hemangiomas
- Vascular Malformations Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- Retinal Diseases and Treatments
- Vascular Anomalies and Treatments
- Platelet Disorders and Treatments
- Lipid metabolism and disorders
- Cellular Mechanics and Interactions
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- High Altitude and Hypoxia
- Tumors and Oncological Cases
- Acute Ischemic Stroke Management
- Cancer, Hypoxia, and Metabolism
- Pulmonary Hypertension Research and Treatments
- Vascular anomalies and interventions
- Venous Thromboembolism Diagnosis and Management
University of Oulu
2012-2024
Matrix Research (United States)
2018
Venous malformations (VMs) are composed of ectatic veins with scarce smooth muscle cell coverage. Activating mutations in the endothelial tyrosine kinase receptor TIE2 a common cause these lesions. VMs deformity, pain, and local intravascular coagulopathy, they expand time. Targeted pharmacological therapies not available for this condition. Here, we generated model by injecting HUVECs expressing most frequent VM-causing mutation, TIE2-L914F, into immune-deficient mice. TIE2-L914F-expressing...
Venous malformations (VMs) are localized defects in vascular morphogenesis frequently caused by mutations the gene for endothelial tyrosine kinase receptor TIE2. Here, we report analysis of a comprehensive collection 22 TIE2 identified patients with VM, either as single amino acid substitutions or double-mutations on same allele. Using cell (EC) cultures, mouse models and ultrastructural tissue biopsies from patients, demonstrate common well mutation-specific cellular molecular features,...
Mutations in the endothelial cell (EC) tyrosine kinase receptor TIE2 cause inherited and sporadic forms of venous malformation. The recurrent somatic mutation L914F common germline R849W differ terms phosphorylation level, as well sub-cellular localization trafficking receptor. Previous studies have shed light on certain pathogenic properties R849W, but mechanisms action are unknown. We used global gene expression profiling to study effects ECs. found that strongly dysregulates genes...
Abstract Hypoxia plays an important regulatory role in the vasculature to adjust blood flow meet metabolic requirements. At level of gene transcription, responses are mediated by hypoxia-inducible factor (HIF) stability which is controlled HIF prolyl 4-hydroxylase-2 (PHD2). In lungs hypoxia results vasoconstriction, however, pathophysiological relevance PHD2 major arterial cell types; endothelial cells (ECs) and smooth muscle (aSMCs) adult incompletely characterized. Here, we investigated...
The maintenance of fluid homeostasis is necessary for function the neural retina; however, little known about significance potential fluid management mechanisms. Here, we investigated angiopoietin-4 (Angpt4, also as Ang3), a poorly characterized ligand endothelial receptor tyrosine kinase Tie2, in mouse retina model. By using genetic reporter, fate mapping, and situ hybridization, found Angpt4 expression specific sub-population astrocytes at site where venous morphogenesis occurs that lower...
Angiopoietin 1 (Ang1) is an activating ligand for the endothelial receptor tyrosine kinase Tie2, whereas Ang2 acts as a context-dependent agonist or antagonist that has destabilizing effect on vasculature. The molecular mechanisms responsible versatile functions of are poorly understood. We show here Ang2, but not Ang1, induces Tie2 translocation to specific cell-matrix contact sites located at distal end focal adhesions. Ang2-specific was associated with distinct activation and downstream...
Abstract Heterozygous mutations in any of three major genes, BRCA1 , BRCA2 and PALB2 are associated with high-risk hereditary breast cancer susceptibility frequently seen as familial disease clustering. is a key interaction partner regulator several vital cellular activities BRCA2, thus required for DNA damage repair alleviation replicative oxidative stress. Little however known about how PALB2-deficiency affects cell function beyond that, especially the three-dimensional setting, also its...