title: Ultrasound Biomicroscopic Imaging for Interleukin-1 Receptor Antagonist-Inhibiting Atherosclerosis and Markers of Inflammation in Atherosclerotic Development in Apolipoprotein-E Knockout Mice.
abstract: We sought to validate the hypothesis that the development of atherosclerosis can be suppressed by the interleukin-1 receptor antagonist (IL-1Ra) in murine models of atherosclerosis in vivo, noninvasively seen by means of high-resolution ultrasound biomicroscopy, and we studied changes in inflammatory markers such as IL-1 and C-reactive protein (CRP) plasma levels in these models of atherosclerosis. We divided IL-1Ra(+/-)/apolipoprotein-E (apoE)(-/-) and IL-1Ra(+/+)/apoE(-/-) mice into 2 age groups, used as atherosclerotic models. The control groups were age-matched IL-1Ra(+/+)/apoE(+/+) mice. Plaque thickness was measured in the ascending aorta in short-axis images by means of ultrasound and histology. Plasma levels of IL-1 and CRP were quantified in the 3 murine groups. At 16 weeks, plaque thickness in the ascending aortas of the IL-1Ra(+/-)/apoE(-/-) mice was significantly greater than that in the IL-1Ra(+/+)/apoE(-/-) mice, on ultrasound and histology (P <0.01). In contrast, at 32 weeks, the differences between these 2 genotypes were not statistically significant. Serum IL-1 levels were lower in the IL-1Ra(+/-)/apoE(-/-) mice than in the IL-1Ra(+/+)/apoE(-/-) mice at 16 and 32 weeks (P <0.05). At 16 weeks, serum CRP levels in the IL-1Ra(+/-)/apoE(-/-) mice were higher than in the IL-1Ra(+/+)/apoE(-/-) mice (P <0.01). Our results suggest that ultrasound biomicroscopy enables evaluation of atherosclerotic lesions in vivo, noninvasively and in real-time, in apoE(-/-) mice. Partial IL-1Ra deficiencies might promote early plaque development in 16-week-old apoE(-/-) mice. The balance of IL-1 and IL-1Ra might influence atherosclerotic development. Finally, CRP might affect the initiation of atherosclerosis, rather than its progression.
authors.forename: Rong-Juan
authors.initials: RJ
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Jiao
authors.initials: J
authors.lastname: Yang
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Luo
authors.forename: Rui-Juan
authors.initials: RJ
authors.lastname: Su
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001018:Aortic Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics / Q000517:prevention & control*; D002097:C-Reactive Protein / Q000378:metabolism; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D018345:Mice, Knockout; D033401:Microscopy, Acoustic; D058226:Plaque, Atherosclerotic
chemical_list: D001057:Apolipoproteins E; C507764:Il1rn protein, mouse; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008055:Lipids; D002097:C-Reactive Protein
keywords: Apolipoproteins E/deficiency/genetics; atherosclerosis/diagnosis/genetics; disease models/animal; inflammation/physiopathology; interleukin-1 receptor antagonist protein; interleukin-1/genetics/physiology; mice, knockout; microscopy/methods; time factors