Hypoxia-Inducible Factor-1α/Vascular Endothelial Growth Factor Pathway for Adventitial Vasa Vasorum Formation in Hypertensive Rat Aorta

Abstract

The roles of adventitial vasa vasorum have been highlighted in vascular wall homeostasis. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in physiological and pathophysiological conditions. However, little is known regarding the changes in adventitial vasa vasorum and the mechanism of the formation in hypertensive arteries. Accordingly, endothelial cell proliferation, adventitial vasa vasorum count, and expression of VEGF signaling axis proteins were examined in the ascending aorta of hypertensive Wistar rats that underwent suprarenal aortic constriction. Hypertension not only induced medial and adventitial thickening but also significantly increased adventitial vasa vasorum count by day 28. Preceding the medial thickening, BrdU+-proliferative endothelial cells were observed in the adventitia but not in the media and intima after day 3; they peaked at day 7 and remained modestly increased at day 28. The BrdU+ endothelial cells showed induction of Ets-1, a transcription factor media...