TY  - JOUR
A1  - Laban, Hebatullah
A1  - Weigert, Andreas
A1  - Zink, Joana Miriam
A1  - Elgheznawy, Amro
A1  - Schürmann, Christoph
A1  - Günther, Lea
A1  - Abdel Malik, Randa
A1  - Bothur, Sabrina
A1  - Wingert, Susanne
A1  - Bremer, Rolf
A1  - Rieger, Michael A.
A1  - Brüne, Bernhard
A1  - Brandes, Ralf
A1  - Fleming, Ingrid
A1  - Benz, Peter M.
T1  - VASP regulates leukocyte infiltration, polarization, and vascular repair after ischemia
T2  - The journal of cell biology
N2  - 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.
KW  - Physiology
KW  - Immunology
KW  - Cytoskeleton
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50049
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-500494
SN  - 1540-8140
SN  - 0021-9525
N1  - This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
VL  - 217
IS  - 4
SP  - 1503
EP  - 1519
PB  - Rockefeller Univ. Press
CY  - New York, NY
ER  -