Involvement of ICAM-1 in the progression of atherosclerosis in APOE-knockout mice.
Recent clinical evidence has indicated that the level of soluble ICAM-1 (sICAM-1) is correlated with the severity of atherosclerosis and can predict future cardiovascular events. Here, using apolipoprotein E (APOE)-deficient mice, we investigated the level of sICAM-1 in parallel with endothelial ICAM-1 expression and aortic atherosclerosis. We also examined the effect of ICAM-1 deficiency during the progression of atherosclerosis using double knockout mice. The level of sICAM-1 increased significantly in parallel with the progression of atherosclerosis in APOE-deficient mice, while the sICAM-1 level remained constant in wild-type mice from 3 to 10 months of age. ICAM-1 staining was detected in virtually all endothelial cells, however, ICAM-1 was expressed strongly in the endothelium overlying atheromatous palque in APOE-deficient mice. Deficiency of ICAM-1 in APOE-deficient mice significantly reduced lesions after 5 and 10 months. The present study supported the notion that the level of sICAM-1 is closely related with the severity of atherosclerosis and cardiovascular events, and also suggested that inhibition of ICAM-1 can delay the progression of atherosclerosis.
Kitagawa
Kazuo
K
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, Yamadaoka, Suita-city, Osaka 565-0871, Japan. kitagawa@medone.med.osaka-u.ac.jp
Matsumoto
Masayasu
M
Sasaki
Tsutomu
T
Hashimoto
Hiroyuki
H
Kuwabara
Keisuke
K
Ohtsuki
Toshiho
T
Hori
Masatsugu
M
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
D001057:Apolipoproteins E; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol