First Author | Vandersmissen I | Year | 2015 |
Journal | J Cell Biol | Volume | 210 |
Issue | 7 | Pages | 1239-56 |
PubMed ID | 26391659 | Mgi Jnum | J:227548 |
Mgi Id | MGI:5701552 | Doi | 10.1083/jcb.201502003 |
Citation | Vandersmissen I, et al. (2015) Endothelial Msx1 transduces hemodynamic changes into an arteriogenic remodeling response. J Cell Biol 210(7):1239-56 |
abstractText | 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. |