Graphical summary. (A–C) During arteriogenic remodeling, an arterial shear stimulus reactivates the endothelium of preexisting collateral arterioles (A), leading to an inflammation-driven whole-vessel outward remodeling response (B and C). Increased shear stress, the primary extrinsic trigger of arteriogenesis, induces the reexpression of MSX1 in the collateral endothelium upon femoral artery ligation, and this reexpression is mediated through an ALK6/BMPR2/ENG–pSMAD1/5/8 signaling cascade. MSX1 subsequently drives endothelial activation toward a proinflammatory state by transcriptionally activating ICAM1 and VCAM1 expression, which render the ECs proadhesive for infiltration of leukocytes, mediating outward collateral remodeling.