MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation

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MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation. / Schlosser, Anders; Pilecki, Bartosz; Hemstra, Line E.; Kejling, Karin; Kristmannsdottir, Gudlaug B.; Wulf-Johansson, Helle; Moeller, Jesper B.; Füchtbauer, Ernst Martin; Nielsen, Ole; Kirketerp-Møller, Katrine; Dubey, Lalit K.; Hansen, Pernille B L; Stubbe, Jane; Wrede, Christoph; Hegermann, Jan; Ochs, Matthias; Rathkolb, Birgit; Schrewe, Anja; Bekeredjian, Raffi; Wolf, Eckhard; Gailus-Durner, Valérie; Fuchs, Helmut; De Angelis, Martin Hrabě; Lindholt, Jes S.; Holmskov, Uffe; Sorensen, Grith L.

I: Arteriosclerosis, Thrombosis, and Vascular Biology, Bind 36, Nr. 1, 01.01.2016, s. 122-133.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Schlosser, A, Pilecki, B, Hemstra, LE, Kejling, K, Kristmannsdottir, GB, Wulf-Johansson, H, Moeller, JB, Füchtbauer, EM, Nielsen, O, Kirketerp-Møller, K, Dubey, LK, Hansen, PBL, Stubbe, J, Wrede, C, Hegermann, J, Ochs, M, Rathkolb, B, Schrewe, A, Bekeredjian, R, Wolf, E, Gailus-Durner, V, Fuchs, H, De Angelis, MH, Lindholt, JS, Holmskov, U & Sorensen, GL 2016, 'MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation', Arteriosclerosis, Thrombosis, and Vascular Biology, bind 36, nr. 1, s. 122-133. https://doi.org/10.1161/ATVBAHA.115.306672

APA

Schlosser, A., Pilecki, B., Hemstra, L. E., Kejling, K., Kristmannsdottir, G. B., Wulf-Johansson, H., Moeller, J. B., Füchtbauer, E. M., Nielsen, O., Kirketerp-Møller, K., Dubey, L. K., Hansen, P. B. L., Stubbe, J., Wrede, C., Hegermann, J., Ochs, M., Rathkolb, B., Schrewe, A., Bekeredjian, R., ... Sorensen, G. L. (2016). MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation. Arteriosclerosis, Thrombosis, and Vascular Biology, 36(1), 122-133. https://doi.org/10.1161/ATVBAHA.115.306672

CBE

Schlosser A, Pilecki B, Hemstra LE, Kejling K, Kristmannsdottir GB, Wulf-Johansson H, Moeller JB, Füchtbauer EM, Nielsen O, Kirketerp-Møller K, Dubey LK, Hansen PBL, Stubbe J, Wrede C, Hegermann J, Ochs M, Rathkolb B, Schrewe A, Bekeredjian R, Wolf E, Gailus-Durner V, Fuchs H, De Angelis MH, Lindholt JS, Holmskov U, Sorensen GL. 2016. MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation. Arteriosclerosis, Thrombosis, and Vascular Biology. 36(1):122-133. https://doi.org/10.1161/ATVBAHA.115.306672

MLA

Schlosser, Anders o.a.. "MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation". Arteriosclerosis, Thrombosis, and Vascular Biology. 2016, 36(1). 122-133. https://doi.org/10.1161/ATVBAHA.115.306672

Vancouver

Schlosser A, Pilecki B, Hemstra LE, Kejling K, Kristmannsdottir GB, Wulf-Johansson H o.a. MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2016 jan 1;36(1):122-133. https://doi.org/10.1161/ATVBAHA.115.306672

Author

Schlosser, Anders ; Pilecki, Bartosz ; Hemstra, Line E. ; Kejling, Karin ; Kristmannsdottir, Gudlaug B. ; Wulf-Johansson, Helle ; Moeller, Jesper B. ; Füchtbauer, Ernst Martin ; Nielsen, Ole ; Kirketerp-Møller, Katrine ; Dubey, Lalit K. ; Hansen, Pernille B L ; Stubbe, Jane ; Wrede, Christoph ; Hegermann, Jan ; Ochs, Matthias ; Rathkolb, Birgit ; Schrewe, Anja ; Bekeredjian, Raffi ; Wolf, Eckhard ; Gailus-Durner, Valérie ; Fuchs, Helmut ; De Angelis, Martin Hrabě ; Lindholt, Jes S. ; Holmskov, Uffe ; Sorensen, Grith L. / MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation. I: Arteriosclerosis, Thrombosis, and Vascular Biology. 2016 ; Bind 36, Nr. 1. s. 122-133.

Bibtex

@article{a3e8ab4d3b7a407b8cacc9e01eaefb8c,
title = "MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation",
abstract = "Objective-Arterial injury stimulates remodeling responses that, when excessive, lead to stenosis. These responses are influenced by integrin signaling in vascular smooth muscle cells (VSMCs). Microfibrillar-associated protein 4 (MFAP4) is an integrin ligand localized to extracellular matrix fibers in the vascular wall. The role of MFAP4 in vascular biology is unknown. We aimed to test the hypothesis that MFAP4 would enhance integrin-dependent VSMC activation. Approach and Results-We produced Mfap4-deficient (Mfap4-/-) mice and performed carotid artery ligation to explore the role of MFAP4 in vascular biology in vivo. Furthermore, we investigated the effects of MFAP4 in neointimal formation ex vivo and in primary VSMC and monocyte cultures in vitro. When challenged with carotid artery ligation, Mfap4-/- mice exhibited delayed neointimal formation, accompanied by early reduction in the number of proliferating medial and neointimal cells, as well as infiltrating leukocytes. Delayed neointimal formation was associated with decreased cross-sectional area of ligated Mfap4-/- carotid arteries resulting in lumen narrowing 28 days after ligation. MFAP4 blockade prohibited the formation of neointimal hyperplasia ex vivo. Moreover, we demonstrated that MFAP4 is a ligand for integrin αVβ3 and mediates VSMC phosphorylation of focal adhesion kinase, migration, and proliferation in vitro. MFAP4-dependent VSMC activation was reversible by treatment with MFAP4-blocking antibodies and inhibitors of focal adhesion kinase and downstream kinases. In addition, we showed that MFAP4 promotes monocyte chemotaxis in integrin αVβ3-dependent manner. Conclusions-MFAP4 regulates integrin αVβ3-induced VSMC proliferation and migration, as well as monocyte chemotaxis, and accelerates neointimal hyperplasia after vascular injury.",
keywords = "carotid stenosis, extracellular matrix proteins, hyperplasia, integrin alphaVbeta3, MFAP4 protein, mouse, muscle, smooth, vascular",
author = "Anders Schlosser and Bartosz Pilecki and Hemstra, {Line E.} and Karin Kejling and Kristmannsdottir, {Gudlaug B.} and Helle Wulf-Johansson and Moeller, {Jesper B.} and F{\"u}chtbauer, {Ernst Martin} and Ole Nielsen and Katrine Kirketerp-M{\o}ller and Dubey, {Lalit K.} and Hansen, {Pernille B L} and Jane Stubbe and Christoph Wrede and Jan Hegermann and Matthias Ochs and Birgit Rathkolb and Anja Schrewe and Raffi Bekeredjian and Eckhard Wolf and Val{\'e}rie Gailus-Durner and Helmut Fuchs and {De Angelis}, {Martin Hrab{\v e}} and Lindholt, {Jes S.} and Uffe Holmskov and Sorensen, {Grith L.}",
year = "2016",
month = jan,
day = "1",
doi = "10.1161/ATVBAHA.115.306672",
language = "English",
volume = "36",
pages = "122--133",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "LIPPINCOTT WILLIAMS & WILKINS",
number = "1",

}

RIS

TY - JOUR

T1 - MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation

AU - Schlosser, Anders

AU - Pilecki, Bartosz

AU - Hemstra, Line E.

AU - Kejling, Karin

AU - Kristmannsdottir, Gudlaug B.

AU - Wulf-Johansson, Helle

AU - Moeller, Jesper B.

AU - Füchtbauer, Ernst Martin

AU - Nielsen, Ole

AU - Kirketerp-Møller, Katrine

AU - Dubey, Lalit K.

AU - Hansen, Pernille B L

AU - Stubbe, Jane

AU - Wrede, Christoph

AU - Hegermann, Jan

AU - Ochs, Matthias

AU - Rathkolb, Birgit

AU - Schrewe, Anja

AU - Bekeredjian, Raffi

AU - Wolf, Eckhard

AU - Gailus-Durner, Valérie

AU - Fuchs, Helmut

AU - De Angelis, Martin Hrabě

AU - Lindholt, Jes S.

AU - Holmskov, Uffe

AU - Sorensen, Grith L.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Objective-Arterial injury stimulates remodeling responses that, when excessive, lead to stenosis. These responses are influenced by integrin signaling in vascular smooth muscle cells (VSMCs). Microfibrillar-associated protein 4 (MFAP4) is an integrin ligand localized to extracellular matrix fibers in the vascular wall. The role of MFAP4 in vascular biology is unknown. We aimed to test the hypothesis that MFAP4 would enhance integrin-dependent VSMC activation. Approach and Results-We produced Mfap4-deficient (Mfap4-/-) mice and performed carotid artery ligation to explore the role of MFAP4 in vascular biology in vivo. Furthermore, we investigated the effects of MFAP4 in neointimal formation ex vivo and in primary VSMC and monocyte cultures in vitro. When challenged with carotid artery ligation, Mfap4-/- mice exhibited delayed neointimal formation, accompanied by early reduction in the number of proliferating medial and neointimal cells, as well as infiltrating leukocytes. Delayed neointimal formation was associated with decreased cross-sectional area of ligated Mfap4-/- carotid arteries resulting in lumen narrowing 28 days after ligation. MFAP4 blockade prohibited the formation of neointimal hyperplasia ex vivo. Moreover, we demonstrated that MFAP4 is a ligand for integrin αVβ3 and mediates VSMC phosphorylation of focal adhesion kinase, migration, and proliferation in vitro. MFAP4-dependent VSMC activation was reversible by treatment with MFAP4-blocking antibodies and inhibitors of focal adhesion kinase and downstream kinases. In addition, we showed that MFAP4 promotes monocyte chemotaxis in integrin αVβ3-dependent manner. Conclusions-MFAP4 regulates integrin αVβ3-induced VSMC proliferation and migration, as well as monocyte chemotaxis, and accelerates neointimal hyperplasia after vascular injury.

AB - Objective-Arterial injury stimulates remodeling responses that, when excessive, lead to stenosis. These responses are influenced by integrin signaling in vascular smooth muscle cells (VSMCs). Microfibrillar-associated protein 4 (MFAP4) is an integrin ligand localized to extracellular matrix fibers in the vascular wall. The role of MFAP4 in vascular biology is unknown. We aimed to test the hypothesis that MFAP4 would enhance integrin-dependent VSMC activation. Approach and Results-We produced Mfap4-deficient (Mfap4-/-) mice and performed carotid artery ligation to explore the role of MFAP4 in vascular biology in vivo. Furthermore, we investigated the effects of MFAP4 in neointimal formation ex vivo and in primary VSMC and monocyte cultures in vitro. When challenged with carotid artery ligation, Mfap4-/- mice exhibited delayed neointimal formation, accompanied by early reduction in the number of proliferating medial and neointimal cells, as well as infiltrating leukocytes. Delayed neointimal formation was associated with decreased cross-sectional area of ligated Mfap4-/- carotid arteries resulting in lumen narrowing 28 days after ligation. MFAP4 blockade prohibited the formation of neointimal hyperplasia ex vivo. Moreover, we demonstrated that MFAP4 is a ligand for integrin αVβ3 and mediates VSMC phosphorylation of focal adhesion kinase, migration, and proliferation in vitro. MFAP4-dependent VSMC activation was reversible by treatment with MFAP4-blocking antibodies and inhibitors of focal adhesion kinase and downstream kinases. In addition, we showed that MFAP4 promotes monocyte chemotaxis in integrin αVβ3-dependent manner. Conclusions-MFAP4 regulates integrin αVβ3-induced VSMC proliferation and migration, as well as monocyte chemotaxis, and accelerates neointimal hyperplasia after vascular injury.

KW - carotid stenosis

KW - extracellular matrix proteins

KW - hyperplasia

KW - integrin alphaVbeta3

KW - MFAP4 protein

KW - mouse

KW - muscle

KW - smooth

KW - vascular

UR - http://www.scopus.com/inward/record.url?scp=84952636777&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.115.306672

DO - 10.1161/ATVBAHA.115.306672

M3 - Journal article

C2 - 26564819

AN - SCOPUS:84952636777

VL - 36

SP - 122

EP - 133

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 1

ER -