Fig. 9.

Experimental design and overview. To test the hypothesis that long-term upregulation of VEGF receptors mediates sustained arterial remodeling in ovine adult sheep, we first measured VEGF levels (arrow 1), which returned to normoxic levels after 110 days of hypoxia. In contrast, hypoxia produced sustained increases in the abundances of both VEGF-R1 and VEGF-R2 in endothelium-denuded carotid artery smooth muscle (arrow 2). Stimulation of smooth muscle VEGF receptor in organ culture (arrow 3) increased the abundance of SMαA and MLC₂₀ (arrow 4) and increased their colocalization. VEGF also decreased the abundance of MLCK. These effects of VEGF replicated the effects of chronic hypoxia, as indicated by the solid lines. In contrast to VEGF, however, hypoxia was without effect on colocalization of MLCK with SMαA but increased colocalization of MLCK with MLC₂₀, as indicated by the dashed lines. Together, the findings support the hypothesis that hypoxic upregulation of VEGF receptors contribute to sustained hypoxic arterial remodeling in adult sheep carotid arteries, particularly in relation to contractile protein abundances.