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Article ; Online: Cytokines regulating lymphangiogenesis.

Sáinz-Jaspeado, Miguel / Claesson-Welsh, Lena

2018 Volume 53, Page(s) 58–63

Abstract: Lymphatic vessels are established by differentiation of lymphendothelial progenitors during embryogenesis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing ones is rare in the healthy adult but takes place during pathological ... ...

Abstract	Lymphatic vessels are established by differentiation of lymphendothelial progenitors during embryogenesis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing ones is rare in the healthy adult but takes place during pathological conditions such as inflammation, tissue repair and tumor growth. Conditions of dysfunctional lymphatics exist after surgical interventions or in certain genetic diseases. A key lymphangiogenic stimulator is vascular endothelial growth factor-C (VEGFC) acting on VEGF receptor-3 (VEGFR3) expressed on lymphendothelial cells. Other cytokines may act directly to regulate lymphangiogenesis positively or negatively, or indirectly by inducing expression of VEGFC. This review describes different known lymphangiogenic cytokines, their mechanism of action and role in lymphangiogenesis in health and disease.
MeSH term(s)	Animals ; Carcinogenesis ; Cell Differentiation ; Cytokines/metabolism ; Endothelial Cells/physiology ; Humans ; Lymphangiogenesis ; Lymphatic Vessels/physiology ; Neoplasms/immunology ; Vascular Endothelial Growth Factor C/metabolism ; Vascular Endothelial Growth Factor Receptor-3/metabolism ; Wound Healing
Chemical Substances	Cytokines ; VEGFC protein, human ; Vascular Endothelial Growth Factor C ; FLT4 protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-3 (EC 2.7.10.1)
Language	English
Publishing date	2018-04-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2018.04.003
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Zs.MG 13: Show issues

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Article ; Online: VE-cadherin junction dynamics in initial lymphatic vessels promotes lymph node metastasis.

Sáinz-Jaspeado, Miguel / Ring, Sarah / Proulx, Steven T / Richards, Mark / Martinsson, Pernilla / Li, Xiujuan / Claesson-Welsh, Lena / Ulvmar, Maria H / Jin, Yi

Life science alliance

2023 Volume 7, Issue 3

Abstract: The endothelial junction component vascular endothelial (VE)-cadherin governs junctional dynamics in the blood and lymphatic vasculature. Here, we explored how lymphatic junction stability is modulated by elevated VEGFA signaling to facilitate metastasis ...

Abstract	The endothelial junction component vascular endothelial (VE)-cadherin governs junctional dynamics in the blood and lymphatic vasculature. Here, we explored how lymphatic junction stability is modulated by elevated VEGFA signaling to facilitate metastasis to sentinel lymph nodes. Zippering of VE-cadherin junctions was established in dermal initial lymphatic vessels after VEGFA injection and in tumor-proximal lymphatics in mice. Shape analysis of pan-cellular VE-cadherin fragments revealed that junctional zippering was accompanied by accumulation of small round-shaped VE-cadherin fragments in the lymphatic endothelium. In mice expressing a mutant VEGFR2 lacking the Y949 phosphosite (
MeSH term(s)	Mice ; Animals ; Lymphatic Metastasis ; Endothelial Cells ; Cadherins/genetics ; Lymphatic Vessels ; src-Family Kinases/genetics
Chemical Substances	cadherin 5 ; Cadherins ; src-Family Kinases (EC 2.7.10.2)
Language	English
Publishing date	2023-12-26
Publishing country	United States
Document type	Journal Article
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202302168
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Intravital imaging-based analysis tools for vessel identification and assessment of concurrent dynamic vascular events.

Honkura, Naoki / Richards, Mark / Laviña, Bàrbara / Sáinz-Jaspeado, Miguel / Betsholtz, Christer / Claesson-Welsh, Lena

Nature communications

2018 Volume 9, Issue 1, Page(s) 2746

Abstract: The vasculature undergoes changes in diameter, permeability and blood flow in response to specific stimuli. The dynamics and interdependence of these responses in different vessels are largely unknown. Here we report a non-invasive technique to study ... ...

Abstract	The vasculature undergoes changes in diameter, permeability and blood flow in response to specific stimuli. The dynamics and interdependence of these responses in different vessels are largely unknown. Here we report a non-invasive technique to study dynamic events in different vessel categories by multi-photon microscopy and an image analysis tool, RVDM (relative velocity, direction, and morphology) allowing the identification of vessel categories by their red blood cell (RBC) parameters. Moreover, Claudin5 promoter-driven green fluorescent protein (GFP) expression is used to distinguish capillary subtypes. Intradermal injection of vascular endothelial growth factor A (VEGFA) is shown to induce leakage of circulating dextran, with vessel-type-dependent kinetics, from capillaries and venules devoid of GFP expression. VEGFA-induced leakage in capillaries coincides with vessel dilation and reduced flow velocity. Thus, intravital imaging of non-invasive stimulation combined with RVDM analysis allows for recording and quantification of very rapid events in the vasculature.
MeSH term(s)	Animals ; Blood Flow Velocity/drug effects ; Blood Flow Velocity/physiology ; Blood Vessels/anatomy & histology ; Blood Vessels/diagnostic imaging ; Blood Vessels/drug effects ; Blood Vessels/physiology ; Claudin-5/genetics ; Claudin-5/metabolism ; Female ; Gene Expression ; Genes, Reporter ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Injections, Intradermal ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Fluorescence, Multiphoton/instrumentation ; Microscopy, Fluorescence, Multiphoton/methods ; Molecular Imaging/instrumentation ; Molecular Imaging/methods ; Promoter Regions, Genetic ; Vascular Endothelial Growth Factor A/administration & dosage
Chemical Substances	Claudin-5 ; Cldn5 protein, mouse ; Vascular Endothelial Growth Factor A ; enhanced green fluorescent protein ; vascular endothelial growth factor A, mouse ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2018-07-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-018-04929-8
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Article ; Online: Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis.

Jin, Yi / Ding, Yindi / Richards, Mark / Kaakinen, Mika / Giese, Wolfgang / Baumann, Elisabeth / Szymborska, Anna / Rosa, André / Nordling, Sofia / Schimmel, Lilian / Akmeriç, Emir Bora / Pena, Andreia / Nwadozi, Emmanuel / Jamalpour, Maria / Holstein, Katrin / Sáinz-Jaspeado, Miguel / Bernabeu, Miguel O / Welsh, Michael / Gordon, Emma /

Franco, Claudio A / Vestweber, Dietmar / Eklund, Lauri / Gerhardt, Holger / Claesson-Welsh, Lena

Nature cardiovascular research

2023 Volume 1, Issue 12, Page(s) 1156–1173

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 ... ...

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
Language	English
Publishing date	2023-10-11
Publishing country	England
Document type	Journal Article
ISSN	2731-0590
ISSN (online)	2731-0590
DOI	10.1038/s44161-022-00172-z
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Article ; Online: Myc-dependent endothelial proliferation is controlled by phosphotyrosine 1212 in VEGF receptor-2.

Testini, Chiara / Smith, Ross O / Jin, Yi / Martinsson, Pernilla / Sun, Ying / Hedlund, Marie / Sáinz-Jaspeado, Miguel / Shibuya, Masabumi / Hellström, Mats / Claesson-Welsh, Lena

EMBO reports

2020 Volume 21, Issue 5, Page(s) e50409

Language	English
Publishing date	2020-05-06
Publishing country	England
Document type	Published Erratum
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.202050409
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Article ; Online: Intravital imaging-based analysis tools for vessel identification and assessment of concurrent dynamic vascular events

Naoki Honkura / Mark Richards / Bàrbara Laviña / Miguel Sáinz-Jaspeado / Christer Betsholtz / Lena Claesson-Welsh

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 10

Abstract: Different stimuli can induce dynamic changes in blood flow velocity, vessel diameter and permeability. Here the authors develop a multi-photon microscopy-based image analysis tool allowing the identification of vessels and the assessment of rapid changes ...

Abstract	Different stimuli can induce dynamic changes in blood flow velocity, vessel diameter and permeability. Here the authors develop a multi-photon microscopy-based image analysis tool allowing the identification of vessels and the assessment of rapid changes in large vascular networks.
Keywords	Science ; Q
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intravital imaging-based analysis tools for vessel identification and assessment of concurrent dynamic vascular events

Naoki Honkura / Mark Richards / Bàrbara Laviña / Miguel Sáinz-Jaspeado / Christer Betsholtz / Lena Claesson-Welsh

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 10

Abstract	Different stimuli can induce dynamic changes in blood flow velocity, vessel diameter and permeability. Here the authors develop a multi-photon microscopy-based image analysis tool allowing the identification of vessels and the assessment of rapid changes in large vascular networks.
Keywords	Science ; Q
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Suppressed Vascular Leakage and Myocardial Edema Improve Outcome From Myocardial Infarction.

Li, Xiujuan / Redfors, Björn / Sáinz-Jaspeado, Miguel / Shi, Shujing / Martinsson, Pernilla / Padhan, Narendra / Scharin Täng, Margareta / Borén, Jan / Levin, Malin / Claesson-Welsh, Lena

Frontiers in physiology

2020 Volume 11, Page(s) 763

Abstract: Aim: The acute phase of myocardial infarction (MI) is accompanied by edema contributing to tissue damage and disease outcome. Here, we aimed to identify the mechanism whereby vascular endothelial growth factor (VEGF)-A induces myocardial edema in the ... ...

Abstract	Aim: The acute phase of myocardial infarction (MI) is accompanied by edema contributing to tissue damage and disease outcome. Here, we aimed to identify the mechanism whereby vascular endothelial growth factor (VEGF)-A induces myocardial edema in the acute phase of MI to eventually promote development of therapeutics to specifically suppress VEGFA-regulated vascular permeability while preserving collateral vessel formation. Methods and results: VEGFA regulates vascular permeability and edema by activation of VEGF receptor-2 (VEGFR2), leading to induction of several signaling pathways including the cytoplasmic tyrosine kinase c-Src. The activated c-Src in turn phosphorylates vascular endothelial (VE)-cadherin, leading to dissociation of endothelial adherens junctions. A particular tyrosine at position 949 in mouse VEGFR2 has been shown to be required for activation of c-Src. Wild-type mice and mice with phenylalanine replacing tyrosine (Y) 949 in VEGFR2 ( Conclusion: Suppression of VEGFA/VEGFR2-regulated vascular permeability leads to diminished edema without affecting vascular density correlating with improved myocardial parameters and survival after MI.
Language	English
Publishing date	2020-07-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2020.00763
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Article ; Online: Phenotypic changes in low-density lipoprotein particles as markers of adverse clinical outcomes in COVID-19.

Carmo, Helison Rafael P / Yoshinaga, Marcos Y / Castillo, Alejandro Rosell / Britto Chaves-Filho, Adriano / Bonilha, Isabella / Barreto, Joaquim / Muraro, Stéfanie Primon / de Souza, Gabriela Fabiano / Davanzo, Gustavo Gastão / Perroud, Maurício W / Lukhna, Kishal / Ntsekhe, Mpiko / Davidson, Sean / Velloso, Licio A / Nadruz, Wilson / Carvalho, Luiz Sérgio F / Sáinz-Jaspeado, Miguel / Farias, Alessandro S / Proença-Módena, José Luiz /

Moraes-Vieira, Pedro M / Karathanasis, Sotirios K / Yellon, Derek / Miyamoto, Sayuri / Remaley, Alan T / Sposito, Andrei C

Molecular genetics and metabolism

2023 Volume 138, Issue 4, Page(s) 107552

Abstract: Background and aims: Low-density lipoprotein (LDL) plasma concentration decline is a biomarker for acute inflammatory diseases, including coronavirus disease-2019 (COVID-19). Phenotypic changes in LDL during COVID-19 may be equally related to adverse ... ...

Abstract	Background and aims: Low-density lipoprotein (LDL) plasma concentration decline is a biomarker for acute inflammatory diseases, including coronavirus disease-2019 (COVID-19). Phenotypic changes in LDL during COVID-19 may be equally related to adverse clinical outcomes. Methods: Individuals hospitalized due to COVID-19 (n = 40) were enrolled. Blood samples were collected on days 0, 2, 4, 6, and 30 (D0, D2, D4, D6, and D30). Oxidized LDL (ox-LDL), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were measured. In a consecutive series of cases (n = 13), LDL was isolated by gradient ultracentrifugation from D0 and D6 and was quantified by lipidomic analysis. Association between clinical outcomes and LDL phenotypic changes was investigated. Results: In the first 30 days, 42.5% of participants died due to Covid-19. The serum ox-LDL increased from D0 to D6 (p < 0.005) and decreased at D30. Moreover, individuals who had an ox-LDL increase from D0 to D6 to over the 90th percentile died. The plasma Lp-PLA2 activity also increased progressively from D0 to D30 (p < 0.005), and the change from D0 to D6 in Lp-PLA2 and ox-LDL were positively correlated (r = 0.65, p < 0.0001). An exploratory untargeted lipidomic analysis uncovered 308 individual lipids in isolated LDL particles. Paired-test analysis from D0 and D6 revealed higher concentrations of 32 lipid species during disease progression, mainly represented by lysophosphatidyl choline and phosphatidylinositol. In addition, 69 lipid species were exclusively modulated in the LDL particles from non-survivors as compared to survivors. Conclusions: Phenotypic changes in LDL particles are associated with disease progression and adverse clinical outcomes in COVID-19 patients and could serve as a potential prognostic biomarker.
MeSH term(s)	Humans ; 1-Alkyl-2-acetylglycerophosphocholine Esterase ; COVID-19 ; Lipoproteins, LDL ; Biomarkers ; Lysophosphatidylcholines
Chemical Substances	1-Alkyl-2-acetylglycerophosphocholine Esterase (EC 3.1.1.47) ; Lipoproteins, LDL ; Biomarkers ; Lysophosphatidylcholines
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1418518-0
ISSN	1096-7206 ; 1096-7192
ISSN (online)	1096-7206
ISSN	1096-7192
DOI	10.1016/j.ymgme.2023.107552
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Article ; Online: Myc-dependent endothelial proliferation is controlled by phosphotyrosine 1212 in VEGF receptor-2.

Testini, Chiara / Smith, Ross O / Jin, Yi / Martinsson, Pernilla / Sun, Ying / Hedlund, Marie / Sáinz-Jaspeado, Miguel / Shibuya, Masabumi / Hellström, Mats / Claesson-Welsh, Lena

EMBO reports

2019 Volume 20, Issue 11, Page(s) e47845

Abstract: Exaggerated signaling by vascular endothelial growth factor (VEGF)-A and its receptor, VEGFR2, in pathologies results in poor vessel function. Still, pharmacological suppression of VEGFA/VEGFR2 may aggravate disease. Delineating VEGFR2 signaling in vivo ... ...

Abstract	Exaggerated signaling by vascular endothelial growth factor (VEGF)-A and its receptor, VEGFR2, in pathologies results in poor vessel function. Still, pharmacological suppression of VEGFA/VEGFR2 may aggravate disease. Delineating VEGFR2 signaling in vivo provides strategies for suppression of specific VEGFR2-induced pathways. Three VEGFR2 tyrosine residues (Y949, Y1212, and Y1173) induce downstream signaling. Here, we show that knock-in of phenylalanine to create VEGFR2 Y1212F in C57Bl/6 and FVB mouse strains leads to loss of growth factor receptor-bound protein 2- and phosphoinositide 3'-kinase (PI3K)p85 signaling. C57Bl/6 Vegfr2
Language	English
Publishing date	2019-09-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.201947845
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