Effect of immune deficiency on lipoproteins and atherosclerosis in male apolipoprotein E-deficient mice
Effect of immune deficiency on lipoproteins and atherosclerosis in male apolipoprotein E-deficient mice
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DOI：
10.1161/01.atv.21.6.1011
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发表时间：
2001-06-01
影响因子：
8.7
通讯作者：
Getz, GS
中科院分区：
文献类型：
--
作者：
Reardon, CA;Blachowicz, L;Getz, GS
为了确定T细胞和B细胞是否影响脂质代谢和动脉粥样硬化，我们将载脂蛋白e缺陷（apoE度）小鼠与重组激活基因2缺陷（RAG2度）小鼠杂交。8周龄时，雄性apoE度小鼠的血浆总胆固醇水平比apoE度RAG2度小鼠高出约20%，即使血浆胆固醇水平相似，apoE度小鼠的血浆甘油三酯水平也高出2.5倍。8周龄时血浆胆固醇水平在400到600毫克/分升之间的雄性小鼠在27周龄和40周龄时被安乐死。在27周龄和40周龄时，apoE“RAG2”小鼠的主动脉根部病变面积分别比免疫正常的apoE度小鼠小81%和57%。相比之下，头臂躯干病变的大小没有差异。在40周龄被安乐死的老鼠身上也得到了类似的结果，这些老鼠8周的胆固醇水平在300到399毫克/分升之间。在apoE“RAG2”小鼠中，较低的胆固醇水平能更深刻地抑制主动脉根部动脉粥样硬化。因此，T细胞和B细胞及其产物在不同部位对动脉粥样硬化的发展有不同的影响。我们还证明了免疫系统对血浆脂质稳态的深远影响。
To determine whether T cells and B cells influence lipid metabolism and atherosclerosis, we crossed apolipoprotein E-deficient (apoE degrees) mice with recombination activating gene 2-deficient (RAG2 degrees) mice. Total plasma cholesterol levels were approximate to 20% higher in male apoE degrees mice compared with the apoE degrees RAG2 degrees mice at 8 weeks of age, and plasma triglyceride levels were 2.5-fold higher in the apoE degrees mice even when plasma cholesterol levels were similar. Male mice with plasma cholesterol levels between 400 and 600 mg/dL at 8 weeks of age were euthanized at 27 and 40 weeks of age. The aortic root lesion area in the apoE"RAG2" mice, compared with that in the immune-competent apoE degrees mice, was 81% and 57% smaller at 27 and 40 weeks of age, respectively. In contrast, there was no difference in the size of the brachiocephalic trunk lesions. Similar results were obtained with mice euthanized at 40 weeks of age that had 8-week cholesterol levels between 300 and 399 mg/dL. In apoE"RAG2" mice, aortic root atherosclerosis was more profoundly suppressed at lower cholesterol levels. Thus, T and B cells and their products differentially influence the development of atherosclerosis at different sites. We also demonstrate a profound effect of the immune system on plasma lipid homeostasis.