Endothelial Msx1 transduces hemodynamic changes into an arteriogenic remodeling response
| Autor: | Michel Koole, Jan Schrooten, Aernout Luttun, Xabier L. Aranguren, Frederik Maes, Nick van Gastel, Ine Vandersmissen, Sander Craps, Lieve Umans, Giulia Coppiello, Geert Carmeliet, Olivier Gheysens, Maarten Depypere, Elizabeth A. V. Jones, Roland Devlieger, An Zwijsen |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
MSX1 Transcription Factor/genetics
Endothelium Knockout Endothelium Vascular/cytology Intercellular Adhesion Molecule-1 Vascular Cell Adhesion Molecule-1 Smad Proteins Hemodynamics/physiology Vascular Remodeling Biology Vascular Cell Adhesion Molecule-1/genetics Bone morphogenetic protein Article Muscle Smooth Vascular Bone Morphogenetic Proteins/genetics Proinflammatory cytokine Mice medicine Animals Smad Proteins/genetics Mechanotransduction Research Articles Intercellular Adhesion Molecule-1/genetics MSX1 Transcription Factor Mice Knockout Vascular Remodeling/physiology Signal Transduction/physiology Cell adhesion molecule Hemodynamics Cell Biology Vascular/cytology Cell biology stomatognathic diseases medicine.anatomical_structure PSI_MIC Muscle Smooth Vascular/cytology Bone Morphogenetic Proteins Knockout mouse Immunology Muscle Endothelium Vascular Smooth Signal transduction Signal Transduction |
| Zdroj: | The Journal of Cell Biology Journal of Cell Biology, 210(7), 1239-56. Rockefeller University Press |
| ISSN: | 0021-9525 |
| Popis: | During peripheral arterial disease, MSX1 acts downstream of BMP–SMAD signaling to transduce the arterial shear stimulus into an arteriogenic remodeling response. MSX1 activates collateral endothelium into a proinflammatory state through ICAM1/VCAM1 up-regulation, resulting in increased leukocyte infiltration and collateral remodeling. Collateral remodeling is critical for blood flow restoration in peripheral arterial disease and is triggered by increasing fluid shear stress in preexisting collateral arteries. So far, no arterial-specific mediators of this mechanotransduction response have been identified. We show that muscle segment homeobox 1 (MSX1) acts exclusively in collateral arterial endothelium to transduce the extrinsic shear stimulus into an arteriogenic remodeling response. MSX1 was specifically up-regulated in remodeling collateral arteries. MSX1 induction in collateral endothelial cells (ECs) was shear stress driven and downstream of canonical bone morphogenetic protein–SMAD signaling. Flow recovery and collateral remodeling were significantly blunted in EC-specific Msx1/2 knockout mice. Mechanistically, MSX1 linked the arterial shear stimulus to arteriogenic remodeling by activating the endothelial but not medial layer to a proinflammatory state because EC but not smooth muscle cellMsx1/2 knockout mice had reduced leukocyte recruitment to remodeling collateral arteries. This reduced leukocyte infiltration in EC Msx1/2 knockout mice originated from decreased levels of intercellular adhesion molecule 1 (ICAM1)/vascular cell adhesion molecule 1 (VCAM1), whose expression was also in vitro driven by promoter binding of MSX1. |
| Databáze: | OpenAIRE |
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