title: Coexistence of hypercholesterolemia and hypertension impairs adventitial vascularization.
abstract: 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.
authors.affiliation: Cardiovascular Research Institute and Internal Medicine III, Kurume University School of Medicine, Kurume, Japan. naikai@med.kurume-u.ac.jp
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kai
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kuwahara
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tokuda
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.forename: Ken
authors.initials: K
authors.lastname: Kusaba
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Niiyama
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tahara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nagata
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism; D006937:Hypercholesterolemia / Q000150:complications* / Q000378:metabolism; D006973:Hypertension / Q000150:complications* / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors