We have shown that adventitial vasa vasorum (AVV) formation is enhanced in hypertensive rat aorta to compensate
hypoxia in the thickened media and that
hypercholesterolemia impairs angiogenesis in rat ischemic hindlimb. Thus, we examined the effects of coexistence of
hypercholesterolemia and
hypertension on AVV formation. In Wistar rats,
hypercholesterolemia was established by high-
cholesterol diet from Day -14 (HC rats), and
hypertension was induced by a suprarenal aortic constriction at Day 0 (HT rats). At Day 28, we studied AVV density, adventitial area, and medial thickness in the ascending aorta of control (standard diet+sham operation), HC, HT, and HC+HT rats (n=5/group). In HC rats, although the adventitial area was modestly increased, the AVV density and medial thickness were unchanged versus controls. In addition to medial thickening, marked enlargement of the adventitial area accompanied by increased AVV density was observed in HT rats, compared with controls. HC+HT rats showed lower AVV density, despite larger adventitial area, than HT rats, whereas the medial thickness was similar in HT and HC+HT rats. Immunohistostaining revealed
hypoxia-inducible factor-1alpha expression in the media only in HC+HT rats but not in the other 3 groups, suggesting persistent medial
hypoxia in HC+HT rats. In conclusion, it is suggested that coexistence of
hypercholesterolemia and
hypertension impairs AVV formation, resulting in insufficient compensation for
hypoxia in the thickened media. Our findings provide an insight into the mechanism of the aggravation of
arteriosclerosis when both
hypercholesterolemia and
hypertension are present.