PortalPublikationenThe ADMA/DDAH pathway regulates VEGF-mediated angiogenesis

The ADMA/DDAH pathway regulates VEGF-mediated angiogenesis

Standard

The ADMA/DDAH pathway regulates VEGF-mediated angiogenesis. / Fiedler, Lorna R; Bachetti, Tiziana; Leiper, James; Zachary, Ian; Chen, Lihua; Renné, Thomas; Wojciak-Stothard, Beata.

in: ARTERIOSCL THROM VAS, Jahrgang 29, Nr. 12, 01.12.2009, S. 2117-24.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Fiedler, LR, Bachetti, T, Leiper, J, Zachary, I, Chen, L, Renné, T & Wojciak-Stothard, B 2009, 'The ADMA/DDAH pathway regulates VEGF-mediated angiogenesis', ARTERIOSCL THROM VAS, Jg. 29, Nr. 12, S. 2117-24. https://doi.org/10.1161/ATVBAHA.109.194035

APA

Fiedler, L. R., Bachetti, T., Leiper, J., Zachary, I., Chen, L., Renné, T., & Wojciak-Stothard, B. (2009). The ADMA/DDAH pathway regulates VEGF-mediated angiogenesis. ARTERIOSCL THROM VAS, 29(12), 2117-24. https://doi.org/10.1161/ATVBAHA.109.194035

Vancouver

Fiedler LR, Bachetti T, Leiper J, Zachary I, Chen L, Renné T et al. The ADMA/DDAH pathway regulates VEGF-mediated angiogenesis. ARTERIOSCL THROM VAS. 2009 Dez 1;29(12):2117-24. https://doi.org/10.1161/ATVBAHA.109.194035

Bibtex

@article{e98a70cc54964e03a72263608a253f0f,
title = "The ADMA/DDAH pathway regulates VEGF-mediated angiogenesis",
abstract = "OBJECTIVE: Asymmetrical dimethylarginine (ADMA) is a nitric oxide synthase (NOS) inhibitor and cardiovascular risk factor associated with angiogenic disorders. Enzymes metabolising ADMA, dimethylarginine dimethylaminohydrolases (DDAH) promote angiogenesis, but the mechanisms are not clear. We hypothesized that ADMA/DDAH modifies endothelial responses to vascular endothelial growth factor (VEGF) by affecting activity of Rho GTPases, regulators of actin polymerization, and focal adhesion dynamics.METHODS AND RESULTS: The effects of ADMA on VEGF-induced endothelial cell motility, focal adhesion turnover, and angiogenesis were studied in human umbilical vein endothelial cells (HUVECs) and DDAH I heterozygous knockout mice. ADMA inhibited VEGF-induced chemotaxis in vitro and angiogenesis in vitro and in vivo in an NO-dependent way. ADMA effects were prevented by overexpression of DDAH but were not associated with decreased proliferation, increased apoptosis, or changes in VEGFR-2 activity or expression. ADMA inhibited endothelial cell polarization, protrusion formation, and decreased focal adhesion dynamics, resulting from Rac1 inhibition after decrease in phosphorylation of vasodilator stimulated phosphoprotein (VASP). Constitutively active Rac1, and to a lesser extent dominant negative RhoA, abrogated ADMA effects in vitro and in vivo.CONCLUSIONS: The ADMA/DDAH pathway regulates VEGF-induced angiogenesis in an NO- and Rac1-dependent manner.",
keywords = "Amidohydrolases, Animals, Apoptosis, Arginine, Cell Adhesion Molecules, Cell Polarity, Cell Proliferation, Cells, Cultured, Chemotaxis, Endothelial Cells, Focal Adhesions, Humans, Mice, Mice, Knockout, Microfilament Proteins, Neovascularization, Physiologic, Neuropeptides, Nitric Oxide, Phosphoproteins, Signal Transduction, Vascular Endothelial Growth Factor A, rac GTP-Binding Proteins, rac1 GTP-Binding Protein",
author = "Fiedler, {Lorna R} and Tiziana Bachetti and James Leiper and Ian Zachary and Lihua Chen and Thomas Renn{\'e} and Beata Wojciak-Stothard",
year = "2009",
month = dec,
day = "1",
doi = "10.1161/ATVBAHA.109.194035",
language = "English",
volume = "29",
pages = "2117--24",
journal = "ARTERIOSCL THROM VAS",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

RIS

TY - JOUR

T1 - The ADMA/DDAH pathway regulates VEGF-mediated angiogenesis

AU - Fiedler, Lorna R

AU - Bachetti, Tiziana

AU - Leiper, James

AU - Zachary, Ian

AU - Chen, Lihua

AU - Renné, Thomas

AU - Wojciak-Stothard, Beata

PY - 2009/12/1

Y1 - 2009/12/1

N2 - OBJECTIVE: Asymmetrical dimethylarginine (ADMA) is a nitric oxide synthase (NOS) inhibitor and cardiovascular risk factor associated with angiogenic disorders. Enzymes metabolising ADMA, dimethylarginine dimethylaminohydrolases (DDAH) promote angiogenesis, but the mechanisms are not clear. We hypothesized that ADMA/DDAH modifies endothelial responses to vascular endothelial growth factor (VEGF) by affecting activity of Rho GTPases, regulators of actin polymerization, and focal adhesion dynamics.METHODS AND RESULTS: The effects of ADMA on VEGF-induced endothelial cell motility, focal adhesion turnover, and angiogenesis were studied in human umbilical vein endothelial cells (HUVECs) and DDAH I heterozygous knockout mice. ADMA inhibited VEGF-induced chemotaxis in vitro and angiogenesis in vitro and in vivo in an NO-dependent way. ADMA effects were prevented by overexpression of DDAH but were not associated with decreased proliferation, increased apoptosis, or changes in VEGFR-2 activity or expression. ADMA inhibited endothelial cell polarization, protrusion formation, and decreased focal adhesion dynamics, resulting from Rac1 inhibition after decrease in phosphorylation of vasodilator stimulated phosphoprotein (VASP). Constitutively active Rac1, and to a lesser extent dominant negative RhoA, abrogated ADMA effects in vitro and in vivo.CONCLUSIONS: The ADMA/DDAH pathway regulates VEGF-induced angiogenesis in an NO- and Rac1-dependent manner.

AB - OBJECTIVE: Asymmetrical dimethylarginine (ADMA) is a nitric oxide synthase (NOS) inhibitor and cardiovascular risk factor associated with angiogenic disorders. Enzymes metabolising ADMA, dimethylarginine dimethylaminohydrolases (DDAH) promote angiogenesis, but the mechanisms are not clear. We hypothesized that ADMA/DDAH modifies endothelial responses to vascular endothelial growth factor (VEGF) by affecting activity of Rho GTPases, regulators of actin polymerization, and focal adhesion dynamics.METHODS AND RESULTS: The effects of ADMA on VEGF-induced endothelial cell motility, focal adhesion turnover, and angiogenesis were studied in human umbilical vein endothelial cells (HUVECs) and DDAH I heterozygous knockout mice. ADMA inhibited VEGF-induced chemotaxis in vitro and angiogenesis in vitro and in vivo in an NO-dependent way. ADMA effects were prevented by overexpression of DDAH but were not associated with decreased proliferation, increased apoptosis, or changes in VEGFR-2 activity or expression. ADMA inhibited endothelial cell polarization, protrusion formation, and decreased focal adhesion dynamics, resulting from Rac1 inhibition after decrease in phosphorylation of vasodilator stimulated phosphoprotein (VASP). Constitutively active Rac1, and to a lesser extent dominant negative RhoA, abrogated ADMA effects in vitro and in vivo.CONCLUSIONS: The ADMA/DDAH pathway regulates VEGF-induced angiogenesis in an NO- and Rac1-dependent manner.

KW - Amidohydrolases

KW - Animals

KW - Apoptosis

KW - Arginine

KW - Cell Adhesion Molecules

KW - Cell Polarity

KW - Cell Proliferation

KW - Cells, Cultured

KW - Chemotaxis

KW - Endothelial Cells

KW - Focal Adhesions

KW - Humans

KW - Mice

KW - Mice, Knockout

KW - Microfilament Proteins

KW - Neovascularization, Physiologic

KW - Neuropeptides

KW - Nitric Oxide

KW - Phosphoproteins

KW - Signal Transduction

KW - Vascular Endothelial Growth Factor A

KW - rac GTP-Binding Proteins

KW - rac1 GTP-Binding Protein

U2 - 10.1161/ATVBAHA.109.194035

DO - 10.1161/ATVBAHA.109.194035

M3 - SCORING: Journal article

C2 - 19778944

VL - 29

SP - 2117

EP - 2124

JO - ARTERIOSCL THROM VAS

JF - ARTERIOSCL THROM VAS

SN - 1079-5642

IS - 12

ER -