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J Cell Biol. 2018 Apr 2;217(4):1503-1519. doi: 10.1083/jcb.201702048. Epub 2018 Mar 5.

VASP regulates leukocyte infiltration, polarization, and vascular repair after ischemia.

Author information

1
Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
2
German Centre of Cardiovascular Research (DZHK), Partner site Rhein-Main, Frankfurt am Main, Germany.
3
Institute of Biochemistry I-Pathobiochemistry, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.
4
Institute for Cardiovascular Physiology, Goethe University, Frankfurt am Main, Germany.
5
LOEWE Center for Cell and Gene Therapy and Department for Medicine, Hematology/Oncology, Goethe University, Frankfurt am Main, Germany.
6
HBB Datenkommunikation and Abrechnungssysteme, Hannover, Germany.
7
Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany benz@vrc.uni-frankfurt.de.

Abstract

In ischemic vascular diseases, leukocyte recruitment and polarization are crucial for revascularization and tissue repair. We investigated the role of vasodilator-stimulated phosphoprotein (VASP) in vascular repair. After hindlimb ischemia induction, blood flow recovery, angiogenesis, arteriogenesis, and leukocyte infiltration into ischemic muscles in VASP-/- mice were accelerated. VASP deficiency also elevated the polarization of the macrophages through increased signal transducer and activator of transcription (STAT) signaling, which augmented the release of chemokines, cytokines, and growth factors to promote leukocyte recruitment and vascular repair. Importantly, VASP deletion in bone marrow-derived cells was sufficient to mimic the increased blood flow recovery of global VASP-/- mice. In chemotaxis experiments, VASP-/- neutrophils/monocytes were significantly more responsive to M1-related chemokines than wild-type controls. Mechanistically, VASP formed complexes with the chemokine receptor CCR2 and β-arrestin-2, and CCR2 receptor internalization was significantly reduced in VASP-/- leukocytes. Our data indicate that VASP is a major regulator of leukocyte recruitment and polarization in postischemic revascularization and support a novel role of VASP in chemokine receptor trafficking.

PMID:
29507126
PMCID:
PMC5881493
DOI:
10.1083/jcb.201702048
[Indexed for MEDLINE]
Free PMC Article

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