Objectives Low density lipoprotein receptor defect mice model by transgenetic technology was used to detect atherosclerosis by Ultrasound Biology (UBM). And evaluate the value of low density lipoprotein receptor defect in atherosclerosis using high-resolution ultrasoundbiomicroscopy (UBM) and histopathology in invivo mice.
Methods Mice that low density lipoprotein receptor gene was knocked out were used, and the wild type mice were used as control animals.
Part 1. Normal chow diet: Three different age groups were 20 weeks, 28 weeks and 36 weeks (all n = 7). Wild type mice were in the same grouping. All mice had normal chow diet.
Part 2. High fat diet: Two groups of LDL-R-/- mice were 28 weeks and 36 weeks (n = 7), with high fat diet 8 and 16 weeks respectively. Wild type mice in the same age were used as normal control groups, and had high fat diet for 8 and 16 weeks, too.
LDL-R-/- mice models and control mice were imaged at the level of the aorta by UBM. The intima-media thickness (IMT) or plaque thickness was measured in the ascending aorta (AAO) short-axis views, and compared with corresponding histological thickness in the same vascular section. The levels of serum CRP, oxidized low density lipoprotein (ox- LDL) and other blood-fat in each group were recorded.
Normal chow diet
No any atherosclerotic plaque was found in all LDL-R-/- and control mice of 20 weeks, 28 weeks and 36 weeks. And the IMT had no difference between LDL-R-/- and same age control mice. IMT in the ascending aorta measured by UBM in LDL-R-/- mice and control mice were correlated with histological measurements from the same vascular region (r = 0.692, P<0.01) .
In 36 weeks group, low density lipoprotein, oxidized low density lipoprotein and CRP were higher than the control mice (p<0.01) . Blood fat was not different between LDL-R-/- mice and control mice in 20 and 28 weeks.
High fat diet
The IMT and/or atherosclerotic plaque thickness of AAO had difference between LDL-R-/- mice and control mice, and it was more significant in 36 weeks.
Blood fat and CRP of LDL-R-/- mice were significantly increased compared with control group in 28 weeks (with high fat diet for 8 weeks). This kind of difference was more remarkably in 36 weeks group (with high fat diet for 16 weeks).
The plaque thickness in the ascending aorta measured by UBM in LDL-R-/- mice and control mice were correlated with histological measurements from the same vascular region (r = 0.813, P<0.01) .
Significant differences in body weights were observed between LDL-R-/- and control mice at the same weeks of age.
With normal chow diet, LDL-R-/- mice were hard to get atherosclerosis. But LDL-R-/- mice were easier mice to get atherosclerosis than wild type with high fat diet, and more severely.
Ultrasound biomicroscopy provides a non-invasive, accurate way to detect atherosclerotic progression in mice in vivo. By measuring maximum IMT in the ascending aorta, UBM was capable of following progression of atherosclerosis in AS models mice.
Serum ox-LDL and CRP is closely related to atherosclerosis, and may be related with the severe degree.
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