Lawn R M, Wade D P, Couse T L, Wilcox J N
Winship Cancer Institute, Division of Hematology/Oncology, Emory University School of Medicine, Atlanta, GA, USA.
Arterioscler Thromb Vasc Biol. 2001 Mar;21(3):378-85. doi: 10.1161/01.atv.21.3.378.
The present study examines the expression of ATP-binding cassette transporter 1 (ABC1) mRNA in normal and atherosclerotic tissues by using in situ hybridization in an effort to better understand the function of this cholesterol transport protein. Samples of normal baboon tissues as well as human normal and atherosclerotic aortas were hybridized with (35)S-labeled ABC1 sense and antisense riboprobes. Widespread expression of ABC1 was observed generally in tissues containing inflammatory cells and lymphocytes. Other noninflammatory cells that were also sites of ABC1 synthesis included the ductal cells of the kidney medulla, Leydig cells in the testis, and glial cells in the baboon cerebellum. Although normal veins and arteries did not express ABC1 mRNA, it was found to be upregulated in the setting of atherosclerosis, where widespread expression was found in macrophages within atherosclerotic lesions. These results are consistent with the proposed role of ABC1 in cholesterol transport in inflammatory cells. The specific upregulation of ABC1 mRNA in the setting of atherosclerosis probably reflects the response of leukocytes to cholesterol loading. However, the presence of ABC1 in ductal cells of the kidney medulla and in the small intestine suggest a more general role for this protein in cholesterol transport in other cell types.
本研究通过原位杂交技术检测正常组织和动脉粥样硬化组织中ATP结合盒转运体1(ABC1)mRNA的表达,以更好地了解这种胆固醇转运蛋白的功能。用(35)S标记的ABC1正义和反义核糖探针与正常狒狒组织以及人类正常和动脉粥样硬化主动脉样本进行杂交。一般在含有炎性细胞和淋巴细胞的组织中观察到ABC1的广泛表达。也是ABC1合成部位的其他非炎性细胞包括肾髓质的导管细胞、睾丸中的Leydig细胞和狒狒小脑的神经胶质细胞。虽然正常静脉和动脉不表达ABC1 mRNA,但发现在动脉粥样硬化情况下其表达上调,在动脉粥样硬化病变内的巨噬细胞中发现广泛表达。这些结果与ABC1在炎性细胞胆固醇转运中所提出的作用一致。动脉粥样硬化情况下ABC1 mRNA的特异性上调可能反映了白细胞对胆固醇负荷的反应。然而,ABC1在肾髓质导管细胞和小肠中的存在表明该蛋白在其他细胞类型的胆固醇转运中具有更广泛的作用。