IMMUNE-COMPLEX MEDIATED VASCULITIS INCREASES CORONARY-ARTERY LIPID-ACCUMULATION IN AUTOIMMUNE-PRONE MRL MICE
IMMUNE-COMPLEX MEDIATED VASCULITIS INCREASES CORONARY-ARTERY LIPID-ACCUMULATION IN AUTOIMMUNE-PRONE MRL MICE
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DOI：
10.1161/01.atv.13.6.932
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发表时间：
1993-06-01
期刊：
影响因子：
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通讯作者：
LUSIS, AJ
中科院分区：
文献类型：
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作者：
QIAO, JH;CASTELLANI, LW;LUSIS, AJ
MRL/lpr小鼠在5月龄时发生严重的自身免疫性疾病和血管炎，而同类系MRL/n小鼠表现出更温和的血管炎，发病年龄更晚。当维持高脂肪、高胆固醇（致动脉粥样硬化）饮食时，MRL/lpr品系小鼠在大冠状动脉和小冠状动脉中都表现出显著的脂质沉积，而MRL/n品系小鼠表现出非常少的脂质积聚。两种菌株在低脂食物饮食中均未表现出脂质蓄积。致动脉粥样硬化饮食诱导高脂血症的两个菌株，但令人惊讶的是，含载脂蛋白B的脂蛋白的致动脉粥样硬化的水平要低得多的MRL/pr小鼠。免疫组织化学研究表明，免疫复合物（免疫球蛋白G和M）、T和B淋巴细胞、巨噬细胞、粒细胞、载脂蛋白B和血清淀粉样蛋白A蛋白存在于患有血管炎和脂质积聚的冠状动脉壁中。到6-7月龄时，致动脉粥样硬化饮食组的MRL/lpr小鼠心肌梗死发生率（53%）高于普通饲料组（14%），而MRL/n小鼠在两种饮食中均未出现心肌梗死。这些结果表明血管炎，高脂血症和动脉脂质蓄积之间存在重要的相互作用。他们支持这样的概念，即在免疫复合物介导的血管炎中血管壁的损伤增加了高脂血症时的脂质沉积。
MRL/lpr mice develop severe autoimmune disease and vasculitis by 5 months of age, whereas congenic strain MRL/n mice exhibit much milder vasculitis with a later age of onset. When maintained on a high-fat, high-cholesterol (atherogenic) diet, strain MRL/lpr mice exhibited a striking deposition of lipid in both the large and small coronary arteries, whereas strain MRL/n mice exhibited very little lipid accumulation. Neither strain exhibited lipid accumulation on a low-fat chow diet. The atherogenic diet induced hyperlipidemia in both strains, but surprisingly the levels of atherogenic apolipoprotein B-containing lipoproteins were much lower in MRL/pr mice. Immunohistochemical studies revealed that immune complexes (immunoglobulins G and M), T and B lymphocytes, macrophages, granulocytes, apolipoprotein B, and serum amyloid A proteins were present in the walls of the coronary arteries that had vasculitis and lipid accumulation. By 6-7 months of age, MRL/lpr mice had a higher incidence of myocardial infarction in the atherogenic diet group (53%) compared with the chow group (14%), whereas MRL/n mice exhibited no myocardial infarction on either diet. These results suggest important interactions between vasculitis, hyperlipidemia, and arterial lipid accumulation. They support the concept that injury to the vessel wall in immune-complex-mediated vasculitis increases lipid deposition in the presence of hyperlipidemia.