Publication Date
8-1-2015
Journal
The Texas Heart Journal
DOI
10.14503/THIJ-14-4318
PMID
26413013
Publication Date(s)
August 2015
Language
English
PMCID
PMC4567116
PubMedCentral® Posted Date
8-1-2015
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Apolipoproteins E/deficiency/genetics, atherosclerosis/diagnosis/genetics, disease models/animal, inflammation/physiopathology, interleukin-1/genetics/physiology, interleukin-1 receptor antagonist protein, mice, knockout, microscopy/methods, time factors
Copyright
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
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.