Watanabe-Heritable Hyperlipidemic Rabbit

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An animal model for studying coronary artery and familial hypercholesterolemia, a condition caused by a deficiency of LDL receptors
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In the case of WHHL rabbits, [[sup.18]F]FDG uptakes in the aorta sections were also observed extensively in both the neointima and media, which were characterized by the presence of invading macrophages and vascular SMCs (Figure 5).
recently reported that [[sup.18]F]FDG-PET signals in atherosclerotic plaques were highly dependent on the number of infiltrated macrophages in the thoracic aorta in WHHL with myocardial infarction [13, 20].
These patterns are similar to those observed in other animal models, although macrophage infiltration into plaques is more evident in the WHHL rabbit model [3-5, 24].
We have also confirmed that [[sup.18]F]FDG accumulation in the WHHL rabbit model is observed in the neointima using ex vivo macro-ARG.
Steinberg, "Low density lipoprotein receptor deficiency in cultured hepatocytes of the WHHL rabbit.
The arterial slices in the normal and WHHL rabbits at age of 6 months ((a-d), normal; (e-h), WHHL).
In spite of this, we found that CRP ASO-treated WHHL rabbits had somewhat higher plasma lipids including TC (starting from 3 weeks, P < 0.05) and TG (starting from 10 weeks, P < 0.05) than controls, (Figure 2) while HDL-C levels were unchanged (data not shown).
Quantitative analysis of the microscopic lesions and macrophage and smooth muscle cell contents along with CRP immunoreactive protein deposition did not reveal any significant differences between CRP ASO-treated WHHL rabbits and controls (Figure 5).
Histological examination revealed that CRP immunoreactive protein contents were slightly reduced in the lesions of CRP ASO-treated WHHL rabbits, but without statistical significance (Figure 9).
In the current study, we first developed rabbit CRP antisense oligonucleotides and then evaluated their effects on WHHL rabbits, a well-established model for the investigation of atherosclerosis.
Unexpectedly, we found that CRP ASO treatment elevated plasma lipids in WHHL rabbits due to enhancement of apoB-containing particle production.
In conclusion, we found that CRP lowering does not have significant influence on the initiation and progression of atherosclerosis in WHHL rabbits; thus, CRP may not be a therapeutic target for the treatment of atherosclerosis.