Macrophage apoAI protects against dyslipidemia-induced dermatitis and atherosclerosis without affecting HDL
Macrophage apoAI protects against dyslipidemia-induced dermatitis and atherosclerosis without affecting HDL
复制标题
DOI：
10.1194/jlr.m056408
复制
发表时间：
2015-03-01
影响因子：
6.5
通讯作者：
Fazio, Sergio
中科院分区：
文献类型：
--
作者：
Tavori, Hagai;Su, Yan Ru;Fazio, Sergio
组织胆固醇积聚、巨噬细胞浸润和炎症是动脉粥样硬化和某些形式的皮炎的特征。HDL及其主要蛋白apoAI是巨噬细胞过量胆固醇的受体，该过程抑制组织炎症。最近的流行病学和临床试验证据质疑HDL及其操纵在心血管疾病中的作用。我们研究了异位巨噬细胞apoAI表达对小鼠高胆固醇血症和HDL缺乏联合诱导的动脉粥样硬化和皮炎的影响。将造血祖细胞转导以表达人apoAI，并移植到致死辐射的LDL受体（-/-）/apoAI（-/）-小鼠中，然后将其置于高脂肪饮食中16周。巨噬细胞apoAI表达降低了主动脉CD 4（+）T细胞水平（-39.8%）、病变大小（-25%）和坏死核心面积（-31.6%），而不影响血清HDL或主动脉巨噬细胞水平。巨噬细胞apoAI降低皮肤胆固醇39.8%，恢复皮肤形态，并降低皮肤CD 4（+）T细胞水平。与对照移植小鼠相比，巨噬细胞apoAI还降低了皮肤引流淋巴结中的CD 4（+）T细胞水平（-32.9%），但对其他T细胞、B细胞、树突状细胞或巨噬细胞没有影响。因此，巨噬细胞apoAI表达通过减少胆固醇积累和调节CD 4（+）T细胞水平来防止动脉粥样硬化和皮炎，而不影响血清HDL或组织巨噬细胞水平。
Tissue cholesterol accumulation, macrophage infi ltration, and infl ammation are features of atherosclerosis and some forms of dermatitis. HDL and its main protein, apoAI, are acceptors of excess cholesterol from macrophages; this process inhibits tissue infl ammation. Recent epidemiologic and clinical trial evidence questions the role of HDL and its manipulation in cardiovascular disease. We investigated the effect of ectopic macrophage apoAI expression on atherosclerosis and dermatitis induced by the combination of hypercholesterolemia and absence of HDL in mice. Hematopoietic progenitor cells were transduced to express human apoAI and transplanted into lethally irradiated LDL receptor(-/-)/apoAI(-/)-mice, which were then placed on a high-fat diet for 16 weeks. Macrophage apoAI expression reduced aortic CD4(+) T-cell levels (-39.8%), lesion size (-25%), and necrotic core area (-31.6%), without affecting serum HDL or aortic macrophage levels. Macrophage apoAI reduced skin cholesterol by 39.8%, restored skin morphology, and reduced skin CD4(+) T-cell levels. Macrophage apoAI also reduced CD4(+) T-cell levels (-32.9%) in skin-draining lymph nodes but had no effect on other T cells, B cells, dendritic cells, or macrophages compared with control transplanted mice. Thus, macrophage apoAI expression protects against atherosclerosis and dermatitis by reducing cholesterol accumulation and regulating CD4(+) T-cell levels, without affecting serum HDL or tissue macrophage levels.