| 1. |
- Claesson-Welsh, Lena, et al.
(författare)
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Tyrosine-protein kinase Yes is essential in vascular barrier dynamics
- 2022
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Ingår i: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590. ; 1:12, s. 1136-1137
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Endothelial cell-cell contacts in blood vessels constitute a barrier to the flux of molecules and cells from blood to tissues. We identified the tyrosine-protein kinase Yes as the principal regulator of collective endothelial cell migration and vascular barrier dynamics, a finding that opens avenues for future therapeutic development.
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| 2. |
- Guillamat-Prats, R, et al.
(författare)
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GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation
- 2022
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Ingår i: Nature cardiovascular research. - : Springer Science and Business Media LLC. - 2731-0590. ; 1, s. 1056-1071
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Tidskriftsartikel (refereegranskat)abstract
- Dissecting the pathways regulating the adaptive immune response in atherosclerosis is of particular therapeutic interest. Here we report that the lipid G-protein-coupled receptor GPR55 is highly expressed by splenic plasma cells (PCs), upregulated in mouse spleens during atherogenesis and human unstable or ruptured compared to stable plaques.Gpr55-deficient mice developed larger atherosclerotic plaques with increased necrotic core size compared to their corresponding controls. Lack of GPR55 hyperactivated B cells, disturbed PC maturation and resulted in IgG overproduction. B-cell-specificGpr55depletion or adoptive transfer ofGpr55-deficient B cells was sufficient to promote plaque development and elevated IgG titers. In vitro, the endogenous GPR55 ligand lysophsophatidylinositol (LPI) enhanced PC proliferation, whereas GPR55 antagonism blocked PC maturation and increased their mitochondrial content. Collectively, these discoveries provide previously undefined evidence for GPR55 in B cells as a key modulator of the adaptive immune response in atherosclerosis.
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| 3. |
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| 4. |
- Jin, Yi, et al.
(författare)
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Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis
- 2022
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Ingår i: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590. ; 1:12, s. 1156-1173
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive leakage, edema and high interstitial pressure. Here we show that the Src-related Yes tyrosine kinase, rather than Src, is localized at endothelial cell (EC) junctions where it becomes activated in a flow-dependent manner. EC-specific Yes1 deletion suppresses VE-cadherin phosphorylation and arrests VE-cadherin at EC junctions. This is accompanied by loss of EC collective migration and exaggerated agonist-induced macromolecular leakage. Overexpression of Yes1 causes ectopic VE-cadherin phosphorylation, while vascular leakage is unaffected. In contrast, in EC-specific Src deficiency, VE-cadherin internalization is maintained and leakage is suppressed. In conclusion, Yes-mediated phosphorylation regulates constitutive VE-cadherin turnover, thereby maintaining endothelial junction plasticity and vascular integrity.
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| 5. |
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| 6. |
- Mauersberger, C, et al.
(författare)
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Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation
- 2022
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Ingår i: Nature cardiovascular research. - : Springer Science and Business Media LLC. - 2731-0590. ; 1:12, s. 1174-1186
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Tidskriftsartikel (refereegranskat)abstract
- Variants in genes encoding the soluble guanylyl cyclase (sGC) in platelets are associated with coronary artery disease (CAD) risk. Here, by using histology, flow cytometry and intravital microscopy, we show that functional loss of sGC in platelets of atherosclerosis-prone Ldlr−/− mice contributes to atherosclerotic plaque formation, particularly via increasing in vivo leukocyte adhesion to atherosclerotic lesions. In vitro experiments revealed that supernatant from activated platelets lacking sGC promotes leukocyte adhesion to endothelial cells (ECs) by activating ECs. Profiling of platelet-released cytokines indicated that reduced platelet angiopoietin-1 release by sGC-depleted platelets, which was validated in isolated human platelets from carriers of GUCY1A1 risk alleles, enhances leukocyte adhesion to ECs. Importantly, pharmacological sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced leukocyte recruitment and atherosclerotic plaque formation in atherosclerosis-prone Ldlr−/− mice. Therefore, pharmacological sGC stimulation might represent a potential therapeutic strategy to prevent and treat CAD.
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| 7. |
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| 8. |
- Richards, Mark, et al.
(författare)
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Targeting VEGF-induced vascular permeability
- 2022
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Ingår i: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590. ; 1:5, s. 413-414
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Blood vascular leakage in conjunction with stroke causes edema and a worsened outcome. Through augmented and selective tyrosine phosphatase activity, endothelial junctions can be sealed, resulting in reduced stroke volume and improved survival.
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| 9. |
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