Lack of interleukin-1beta decreases the severity of atherosclerosis in ApoE-deficient mice.
OBJECTIVE
Atherosclerosis is considered to be a chronic inflammatory disease and many cytokines participate in the development of atherosclerosis. We focused on the role of interleukin-1beta (IL-1beta), one of the proinflammatory cytokines secreted by monocytes/macrophages, in the progression of atherosclerosis.


RESULTS
We generated mice lacking both apoE and IL-1beta. The sizes of atherosclerotic lesions at the aortic sinus in apoE-/-/IL-1beta-/-mice at 12 and 24 weeks of age showed a significant decrease of approximately 30% compared with apoE-/-/IL-1beta+/+ mice, and the percentage of the atherosclerotic area to total area of apoE-/-/IL-1beta-/- at 24 weeks of age also showed a significant decrease of about 30% compared with apoE-/-/IL-1beta+/+. The mRNA levels of vascular cell adhesion molecule (VCAM)-1 and monocyte chemotactic protein-1 in the apoE-/-/IL-1beta-/- aorta were significantly reduced compared with the apoE-/-/IL-1beta+/+. Furthermore, VCAM-1 was also reduced at the protein level in apoE-/-/IL-1beta-/- aorta compared with apoE-/-/IL-1beta+/+.


CONCLUSIONS
The lack of IL-1beta decreases the severity of atherosclerosis in apoE deficient mice, possibly through increased expressions of VCAM-1 and monocyte chemotactic protein-1 in the aorta.
Kirii
Hirokazu
H
Department of Clinical Laboratory Medicine, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan.
Niwa
Tamikazu
T
Yamada
Yasuhiro
Y
Wada
Hisayasu
H
Saito
Kuniaki
K
Iwakura
Yoichiro
Y
Asano
Masahide
M
Moriwaki
Hisataka
H
Seishima
Mitsuru
M
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001024:Aortic Valve Stenosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000502:physiology*; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000172:deficiency / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D017539:Tunica Intima / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
D001057:Apolipoproteins E; D018932:Chemokine CCL2; D007375:Interleukin-1; D008055:Lipids; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1