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Platelet Bone Morphogenetic Protein-4 Mediates Vascular Inflammation and Neointima Formation after Arterial Injury

Authors :
Marietta Jank
Nikolaus von Niessen
Christoph B. Olivier
Hannah Schmitt
Nathaly Anto-Michel
Ingo Hilgendorf
Christoph Bode
Martin Moser
Jennifer S. Esser
Qian Zhou
Source :
Cells, Vol 10, Iss 8, p 2027 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

The purpose of this study is to investigate the role of platelet bone morphogenetic proteins (BMP)-4 during vascular inflammation and remodeling in a mouse model of carotid wire injury. Transgenic mice with a platelet-specific deletion of BMP-4 (BMP4Plt−/−) were generated. Intravital microscopy was performed to evaluate leukocyte adhesion to the vessel wall. Expression of adhesion molecules and chemokines were analyzed. Platelet-leukocyte aggregates (PLAs) were evaluated using flow cytometry. For carotid wire injury, BMP4Plt−/− mice were further crossed with LDLr−/− mice (BMP4Plt−/−/LDLr−/−) and fed with a high cholesterol diet for 2-weeks. Carotid wire injury was performed, and re-endothelialization and neointimal formation were evaluated. In comparison to the control mice, stimulation with TNFα resulted in fewer rolling and adherent leukocytes to the vessel wall in the BMP4Plt−/− mice. mRNA and protein expression of P-selectin and adhesion molecules were reduced in the aorta of the BMP4Plt−/− mice. In platelets from the BMP4Plt−/− mice, the expression of P-selectin was reduced, and fewer PLA formations were measured than in the control mice. Loss of platelet BMP-4 further prevented neointima formation after carotid wire injury. Endothelial regeneration after injury was decelerated in the BMP4Plt−/− mice, and confirmed in-vitro, where the deletion of platelet BMP-4 inhibited endothelial cell proliferation and migration. We demonstrate for the first time that platelet BMP-4 is involved during vascular inflammation and remodeling. This is partially mediated by the inhibition of platelet activation, reduced expression of adhesion molecules and inflammatory responses. Our findings identify platelet BMP-4 as a mediator of vascular inflammation in early atherosclerosis and restenosis.

Details

Language :
English
ISSN :
20734409
Volume :
10
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.3ec455d718f645d1844c08adce60cac4
Document Type :
article
Full Text :
https://doi.org/10.3390/cells10082027