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.