Chronic hypoxia accelerates the progression of atherosclerosis in apolipoprotein E-knockout mice.
The aim of this study was to investigate the effect of chronic hypoxia on the development and progression of atherosclerosis in apolipoprotein E-knockout (apoE-KO) mice. Male and female apoE-KO mice (6 weeks old) and age- and sex-matched wild-type mice were kept under hypoxic conditions (10.0 +/- 0.5% O2) in a gas chamber or in room air for 3 weeks. Aortic atherosclerotic plaque was not observed in wild-type mice under normoxic or hypoxic conditions. In the apoE-KO mice, however, hypoxia induced proliferation of smooth muscle cells and plaque formation in the aorta, which were not observed under normoxic conditions. Although sexual dimorphism of the response to hypoxia was not observed, these hypoxia-induced atherogenic changes were accompanied by a significant increase of plasma low density lipoprotein (LDL) cholesterol and NADPH-dependent vascular superoxide (O2-) production. Furthermore, matrix metalloproteinase (MMP)-9 was activated in the aorta of apoE-KO mice. In conclusion, chronic hypoxia accelerated the development of atherosclerosis in apoE-KO mice, along with increased O2- production and activated MMP-9 in the aorta.
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Daisuke
D
Nakano
Tetsuya
T
Hayashi
Naoko
N
Tazawa
Chika
C
Yamashita
Sakiko
S
Inamoto
Nobuaki
N
Okuda
Tatsuhiko
T
Mori
Koichi
K
Sohmiya
Yasushi
Y
Kitaura
Yoshikatsu
Y
Okada
Yasuo
Y
Matsumura
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D002908:Chronic Disease; D005260:Female; D000860:Hypoxia / Q000150:complications*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000378:metabolism
D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D013481:Superoxides; D002784:Cholesterol; D020780:Matrix Metalloproteinase 9