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MAP-Kinase Activated Protein Kinase 2 Links Endothelial Activation and Monocyte/macrophage Recruitment in Arteriogenesis

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MAP-Kinase Activated Protein Kinase 2 Links Endothelial Activation and Monocyte/macrophage Recruitment in Arteriogenesis. / Limbourg, Anne; von Felden, Johann; Jagavelu, Kumaravelu; Krishnasamy, Kashyap; Napp, L Christian; Kapopara, Piyushkumar R; Gaestel, Matthias; Schieffer, Bernhard; Bauersachs, Johann; Limbourg, Florian P; Bavendiek, Udo.

In: PLOS ONE, Vol. 10, No. 10, 2015, p. e0138542.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Limbourg, A, von Felden, J, Jagavelu, K, Krishnasamy, K, Napp, LC, Kapopara, PR, Gaestel, M, Schieffer, B, Bauersachs, J, Limbourg, FP & Bavendiek, U 2015, 'MAP-Kinase Activated Protein Kinase 2 Links Endothelial Activation and Monocyte/macrophage Recruitment in Arteriogenesis', PLOS ONE, vol. 10, no. 10, pp. e0138542. https://doi.org/10.1371/journal.pone.0138542

APA

Limbourg, A., von Felden, J., Jagavelu, K., Krishnasamy, K., Napp, L. C., Kapopara, P. R., Gaestel, M., Schieffer, B., Bauersachs, J., Limbourg, F. P., & Bavendiek, U. (2015). MAP-Kinase Activated Protein Kinase 2 Links Endothelial Activation and Monocyte/macrophage Recruitment in Arteriogenesis. PLOS ONE, 10(10), e0138542. https://doi.org/10.1371/journal.pone.0138542

Vancouver

Limbourg A, von Felden J, Jagavelu K, Krishnasamy K, Napp LC, Kapopara PR et al. MAP-Kinase Activated Protein Kinase 2 Links Endothelial Activation and Monocyte/macrophage Recruitment in Arteriogenesis. PLOS ONE. 2015;10(10):e0138542. https://doi.org/10.1371/journal.pone.0138542

Bibtex

@article{a28d9d21335b47c1a64005d60e194539,
title = "MAP-Kinase Activated Protein Kinase 2 Links Endothelial Activation and Monocyte/macrophage Recruitment in Arteriogenesis",
abstract = "Arteriogenesis, the growth of natural bypass arteries, is triggered by hemodynamic forces within vessels and requires a balanced inflammatory response, involving induction of the chemokine MCP-1 and recruitment of leukocytes. However, little is known how these processes are coordinated. The MAP-kinase-activated-proteinkinase-2 (MK2) is a critical regulator of inflammatory processes and might represent an important link between cytokine production and cell recruitment during postnatal arteriogenesis. Therefore, the present study investigated the functional role of MK2 during postnatal arteriogenesis. In a mouse model of hindlimb ischemia (HLI) MK2-deficiency (MK2KO) significantly impaired ischemic blood flow recovery and growth of collateral arteries as well as perivascular recruitment of mononuclear cells and macrophages. This was accompanied by induction of endothelial MCP-1 expression in wildtype (WT) but not in MK2KO collateral arteries. Following HLI, MK2 activation rapidly occured in the endothelium of growing WT arteries in vivo. In vitro, inflammatory cytokines and cyclic stretch activated MK2 in endothelial cells, which was required for stretch- and cytokine-induced release of MCP-1. In addition, a monocyte cell autonomous function of MK2 was uncovered potentially regulating MCP-1-dependent monocyte recruitment to vessels: MCP-1 stimulation of WT monocytes induced MK2 activation and monocyte migration in vitro. The latter was reduced in MK2KO monocytes, while in vivo MK2 was activated in monocytes recruited to collateral arteries. In conclusion, MK2 regulates postnatal arteriogenesis by controlling vascular recruitment of monocytes/macrophages in a dual manner: regulation of endothelial MCP-1 expression in response to hemodynamic and inflammatory forces as well as MCP-1 dependent monocyte migration.",
keywords = "Animals, Arteries, Cells, Cultured, Chemokine CCL2, Chemotaxis, Endothelium, Vascular, Intracellular Signaling Peptides and Proteins, Macrophages, Mice, Monocytes, Protein-Serine-Threonine Kinases, Journal Article, Research Support, Non-U.S. Gov't",
author = "Anne Limbourg and {von Felden}, Johann and Kumaravelu Jagavelu and Kashyap Krishnasamy and Napp, {L Christian} and Kapopara, {Piyushkumar R} and Matthias Gaestel and Bernhard Schieffer and Johann Bauersachs and Limbourg, {Florian P} and Udo Bavendiek",
year = "2015",
doi = "10.1371/journal.pone.0138542",
language = "English",
volume = "10",
pages = "e0138542",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

RIS

TY - JOUR

T1 - MAP-Kinase Activated Protein Kinase 2 Links Endothelial Activation and Monocyte/macrophage Recruitment in Arteriogenesis

AU - Limbourg, Anne

AU - von Felden, Johann

AU - Jagavelu, Kumaravelu

AU - Krishnasamy, Kashyap

AU - Napp, L Christian

AU - Kapopara, Piyushkumar R

AU - Gaestel, Matthias

AU - Schieffer, Bernhard

AU - Bauersachs, Johann

AU - Limbourg, Florian P

AU - Bavendiek, Udo

PY - 2015

Y1 - 2015

N2 - Arteriogenesis, the growth of natural bypass arteries, is triggered by hemodynamic forces within vessels and requires a balanced inflammatory response, involving induction of the chemokine MCP-1 and recruitment of leukocytes. However, little is known how these processes are coordinated. The MAP-kinase-activated-proteinkinase-2 (MK2) is a critical regulator of inflammatory processes and might represent an important link between cytokine production and cell recruitment during postnatal arteriogenesis. Therefore, the present study investigated the functional role of MK2 during postnatal arteriogenesis. In a mouse model of hindlimb ischemia (HLI) MK2-deficiency (MK2KO) significantly impaired ischemic blood flow recovery and growth of collateral arteries as well as perivascular recruitment of mononuclear cells and macrophages. This was accompanied by induction of endothelial MCP-1 expression in wildtype (WT) but not in MK2KO collateral arteries. Following HLI, MK2 activation rapidly occured in the endothelium of growing WT arteries in vivo. In vitro, inflammatory cytokines and cyclic stretch activated MK2 in endothelial cells, which was required for stretch- and cytokine-induced release of MCP-1. In addition, a monocyte cell autonomous function of MK2 was uncovered potentially regulating MCP-1-dependent monocyte recruitment to vessels: MCP-1 stimulation of WT monocytes induced MK2 activation and monocyte migration in vitro. The latter was reduced in MK2KO monocytes, while in vivo MK2 was activated in monocytes recruited to collateral arteries. In conclusion, MK2 regulates postnatal arteriogenesis by controlling vascular recruitment of monocytes/macrophages in a dual manner: regulation of endothelial MCP-1 expression in response to hemodynamic and inflammatory forces as well as MCP-1 dependent monocyte migration.

AB - Arteriogenesis, the growth of natural bypass arteries, is triggered by hemodynamic forces within vessels and requires a balanced inflammatory response, involving induction of the chemokine MCP-1 and recruitment of leukocytes. However, little is known how these processes are coordinated. The MAP-kinase-activated-proteinkinase-2 (MK2) is a critical regulator of inflammatory processes and might represent an important link between cytokine production and cell recruitment during postnatal arteriogenesis. Therefore, the present study investigated the functional role of MK2 during postnatal arteriogenesis. In a mouse model of hindlimb ischemia (HLI) MK2-deficiency (MK2KO) significantly impaired ischemic blood flow recovery and growth of collateral arteries as well as perivascular recruitment of mononuclear cells and macrophages. This was accompanied by induction of endothelial MCP-1 expression in wildtype (WT) but not in MK2KO collateral arteries. Following HLI, MK2 activation rapidly occured in the endothelium of growing WT arteries in vivo. In vitro, inflammatory cytokines and cyclic stretch activated MK2 in endothelial cells, which was required for stretch- and cytokine-induced release of MCP-1. In addition, a monocyte cell autonomous function of MK2 was uncovered potentially regulating MCP-1-dependent monocyte recruitment to vessels: MCP-1 stimulation of WT monocytes induced MK2 activation and monocyte migration in vitro. The latter was reduced in MK2KO monocytes, while in vivo MK2 was activated in monocytes recruited to collateral arteries. In conclusion, MK2 regulates postnatal arteriogenesis by controlling vascular recruitment of monocytes/macrophages in a dual manner: regulation of endothelial MCP-1 expression in response to hemodynamic and inflammatory forces as well as MCP-1 dependent monocyte migration.

KW - Animals

KW - Arteries

KW - Cells, Cultured

KW - Chemokine CCL2

KW - Chemotaxis

KW - Endothelium, Vascular

KW - Intracellular Signaling Peptides and Proteins

KW - Macrophages

KW - Mice

KW - Monocytes

KW - Protein-Serine-Threonine Kinases

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.pone.0138542

DO - 10.1371/journal.pone.0138542

M3 - SCORING: Journal article

C2 - 26431421

VL - 10

SP - e0138542

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 10

ER -