Fig. 7. A proposed model for the preferential recruitment of vascular smooth muscle cells to arteries.

a During the early development of arterial and venous blood vessels the CXCL12 ligand, its receptor CXCR4, and the vascular smooth muscle cell (vSMC) chemoattractant PDGFB are all more highly expressed on arteries than on veins. In contrast, KLF2 is more highly expressed on primitive veins than arteries. b A proposed molecular pathway for preferential recruitment of vSMCs to arteries. In arteries, autocrine activation of endothelial CXCR4 by its CXCL12 ligand results in increased production of PDGFB by arterial endothelium, promoting vSMC recruitment to arteries. Expression of KLF2 in primitive veins suppresses expression of CXCL12 and CXCR4, preventing upregulation of PDGFB and limiting vSMC recruitment to veins. The cues directing preferential expression of KLF2 in veins remain unclear, but may involve different types of flow (i.e., pulsatile vs. laminar).