Genes within the MHC region have a dramatic influence on radiation-enhanced atherosclerosis in mice.
Genes within the MHC region have a dramatic influence on radiation-enhanced atherosclerosis in mice.
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DOI：
10.1161/circgenetics.110.957449
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发表时间：
2010-10
期刊：
影响因子：
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通讯作者：
Matsumoto AH
中科院分区：
文献类型：
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作者：
Shi W;Zhang Z;Chen MH;Angle JF;Matsumoto AH
当载脂蛋白E （apoE−/−）缺乏或饲喂致动脉粥样硬化饮食时，C3H/HeJ （C3H）小鼠的动脉粥样硬化病变比C57BL/6 （B6）小鼠小得多。这两个菌株的H2单倍型不同，B6有H2b， C3H有H2k。C3。SW-H2b/SnJ （C3.SW）是C3H/HeJ的同源菌株，其中H2k被H2b取代。我们进行了骨髓移植，发现动脉粥样硬化抵抗C3.SW。用C3.SW的骨髓重组apoE−/−小鼠。apoE−/−或B6。致死照射后的apoE - / -小鼠的动脉粥样硬化病变明显大于B6。apoE−/−小鼠接受相同的治疗，损伤比C3H大得多。用同基因骨髓重组apoE−/−小鼠。对于同基因移植，C3.SW。apoE−/−小鼠的病变大小比C3H增加了21倍。apoE−/−小鼠（152,800±21,937对7,060±2,290 μm2/切片），比B6增加近4倍。apoE−/−小鼠（40,529±4,675 μm2/切片）。C3.SW。同基因骨髓重组的apoE−/−小鼠的病变形成比B6骨髓重组的apoE−/−小鼠的病变形成增强（152800±21937 vs 107000±9374 μm2/切片，P=0.067）。亚致死照射导致C3.SW病变大小增加6倍。apoE−/−小鼠（9,795±2,804对1,550±607 μm2/切片；P=0.008）。野生型C3。用apoE+/+或apoE−/−骨髓重建的SW小鼠，其动脉粥样硬化病变明显大于用相同的致动脉粥样硬化饮食治疗的C3H小鼠。这些结果表明，H2区域内的基因对辐射增强的动脉粥样硬化有显著影响，其作用部分通过骨髓源性细胞传递。
C3H/HeJ (C3H) mice develop much smaller atherosclerotic lesions than C57BL/6 (B6) mice when deficient in apolipoprotein E (apoE−/−) or fed an atherogenic diet. The two strains differ in H2 haplotypes with B6 having H2b and C3H having H2k. C3.SW-H2b/SnJ (C3.SW) is a congenic strain of C3H/HeJ in which H2k is replaced with H2b. We performed bone marrow transplantation and found that atherosclerosis-resistant C3.SW.apoE−/− mice reconstituted with bone marrow from either C3.SW.apoE−/− or B6.apoE−/− mice after lethal irradiation developed significantly larger atherosclerotic lesions than B6.apoE−/− mice receiving identical treatments and much larger lesions than C3H.apoE−/− mice reconstituted with syngeneic bone marrow. For syngeneic transplantation, C3.SW.apoE−/− mice exhibited a 21-fold increase in lesion size over C3H.apoE−/− mice (152,800±21,937 vs. 7,060±2,290 μm2/section) and a near 4-fold increase over B6.apoE−/− mice (40,529±4,675 μm2/section). C3.SW.apoE−/− mice reconstituted with syngeneic marrow exhibited enhanced lesion formation relative to those reconstituted with B6 marrow (152,800±21,937 vs. 107,000±9,374 μm2/section; P=0.067). Sublethal irradiation led to a 6-fold increase of lesion size in C3.SW.apoE−/− mice (9,795±2,804 vs. 1,550±607 μm2/section; P=0.008). Wild-type C3.SW mice reconstituted with apoE+/+ or apoE−/− bone marrow developed significantly larger atherosclerotic lesions than C3H mice receiving identical treatments on an atherogenic diet. These results indicate that gene(s) within the H2 region have a dramatic impact on radiation-enhanced atherosclerosis and their effect is conveyed partially through bone marrow-derived cells.