Fig. 1.

Summary of our approach to test the hypothesis that VEGF contributes to hypoxic vascular remodeling through changes in abundance, organization, and function of contractile proteins in fetal arteries. First, we propose that hypoxia induces short-term increases in VEGF (arrow 1) through upregulation of the transcription factor hypoxia-inducible factor. We further propose that these increases in VEGF act on VEGF receptors (VEGF R1/R2) expressed by smooth muscle cells (arrow 2). In addition, we propose that chronic hypoxia increases expression of smooth muscle VEGF receptors (arrow 3). Finally, we propose that activation of smooth muscle VEGF receptors leads to changes in contractile protein abundance and organization that result in changes in arterial structure and function (arrow 4). In this manner, we propose that hypoxic increases in VEGF mediate not only microcirculatory angiogenesis, but also arterial remodeling. Separate experiments were performed to test each of the numbered arrows in fetal arteries.