T and B lymphocytes play a minor sole in atherosclerotic plaque formation in the apolipoprotein E-deficient mouse
T and B lymphocytes play a minor sole in atherosclerotic plaque formation in the apolipoprotein E-deficient mouse
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DOI：
10.1073/pnas.94.9.4642
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发表时间：
1997-04-29
影响因子：
11.1
通讯作者：
Smith, JD
中科院分区：
文献类型：
--
作者：
Dansky, HM;Charlton, SA;Smith, JD
细胞免疫和体液免疫参与了动脉粥样硬化的发病机制。为了确定完整的免疫系统是否是动脉粥样硬化病变形成所必需的，我们通过将载脂蛋白E（apoE）缺陷小鼠与重组酶激活基因I（Rag-1）敲除小鼠杂交，在apoE和Rag-1（E0/R0）中靶向破坏的Chow喂养的免疫缺陷小鼠在16周龄时主动脉根部病变大小减少2倍，与Rag-1基因座（E0/R1）杂合子的免疫活性同窝仔相比，几乎所有来自普通饲料喂养的动物的动脉粥样硬化病变仅限于凸起的泡沫细胞脂肪条纹。相比之下，当第二组动物喂食高脂肪西式饮食以加速病变发展时，主动脉根部病变大小或病变占总主动脉的百分比均无差异，在喂食西式饮食的E0/R0和E0/R1动物中均检测到具有明确帽和坏死核心的纤维斑块。我们的结论是T和IZ淋巴细胞在泡沫细胞病变的形成率中仅起次要作用，并且它们对于纤维增生性斑块的形成不是必需的。
Cellular and humoral immunity have been implicated in the pathogenesis of atherosclerosis. To determine whether an intact immune system is necessary for the formation of atherosclerotic lesions, we have generated immunodeficient mice with hypercholesterolemia and atherosclerosis by crossbreeding the apolipoprotein E (apoE)-deficient mouse with the recombinase activating gene I (Rag-1) knockout mouse, Chow-fed immunodeficient mice with targeted disruption in both apoE and Rag-1 (E0/R0) had a a 2-fold decrement in aortic root lesion size at 16 weeks of age, compared with immunocompetent littermates, which were heterozygotes at the Rag-1 locus (E0/R1), Nearly all atherosclerotic lesions from chow-fed animals were limited to raised foam cell fatty streaks. In contrast, when a second group of animals was fed a high-fat Western-type diet to accelerate lesion development, there were no differences in either aortic root lesion size or the percent of the total aorta occupied by lesions, Fibrous plaques with well-defined caps and necrotic cores were detected in both Western diet-fed E0/R0 and E0/R1 animals. We conclude that T and IZ lymphocytes play only a minor role in the rate of forming foam cell lesions, and they are not necessary for the formation of fibroproliferative plaques.