Leukocyte ABC-transporter A1 and LDL Receptor Play Independent Roles in Atherosclerosis :the Potenti

来源 :第十二次全国动脉硬化性疾病学术会议 | 被引量 : 0次 | 上传用户:darkelf696
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  Objective The present study aims to investigate whether LDL receptor (LDLR) deficiency influences the atheroprotective effects of leukocyte ABC-transporter A1 (ABCA1) in vivo.Methods and Results LDLR-/-mice were transplanted with bone marrow from LDLR-/-/ABCA1-/-mice, LDLR +/+/ABCA1-/-mice, and their respective controls.Although leukocyte ABCA1 deficiency reduced plasma cholesterol levels, after 8 weeks of Western-type diet feeding, animals transplanted with LDLR-/-/ABCA1-/-and LDLR +/+/ABCA1-/-bone marrow developed 1.6-fold (P <0.01) and 1.4-fold (P <0.05) larger lesions, compared to their respective controls.This clearly indicates that the atheroprotection of leukocyte ABCA1 is not affected by LDLR.Two-way ANOVA analysis also demonstrated that deletion of the leukocyte LDLR reduced lesion development (P <0.001) , especially in the absence of leukocyte ABCA1.However, leukocyte LDLR deficiency does not affect monocytosis, recruitment of moncocytes and macrophage foam cell formation.Interestingly, the deletion of leukocyte ABCA1 did reduce lymphocytosis and recruitment of T cells into the adventitia of lesions.These effects are associated with smaller lesion size in LDLR-/-/ABCA1-/-transplanted mice, indicating the potential contribution of lymphocytosis and recruitment of T cells to atherogenesis.Conclusions Leukocyte LDLR deficiency does not affect the atheroprotective effects of leukocyte ABCA1, and vice versa.Furthermore, suppression of lymphocytosis and T cell recruitment into the adventitia could contribute to the atheroprotection of leukocyte LDLR deficiency and ABCA1.
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