Nifedipine inhibits ox-LDL-induced lipid accumulation in human blood-derived macrophages.
Nifedipine inhibits ox-LDL-induced lipid accumulation in human blood-derived macrophages.
复制标题
DOI：
10.1016/j.bbrc.2015.01.010
复制
发表时间：
2015-02
影响因子：
3.1
通讯作者：
Qian Zhang;A. Z. Sha Ma;Chan Wang;Weize Tang;Zhiyuan Song
中科院分区：
文献类型：
--
作者：
Qian Zhang;A. Z. Sha Ma;Chan Wang;Weize Tang;Zhiyuan Song
研究表明，硝苯地平，一种抗高血压药物，防止动脉粥样硬化的进展，但潜在的机制仍然是难以捉摸的。氧化低密度脂蛋白（ox-LDL）与动脉粥样硬化中的巨噬细胞脂质沉积密切相关。在这项研究中，我们研究了硝苯地平对人血源性巨噬细胞中一些ox-LDL相关变化的影响。我们从正常人血液中分离单核细胞并将其分化为巨噬细胞。然后，我们用ox-LDL和/或硝苯地平处理这些人巨噬细胞，并检测脂质积聚和两种受体CD 36和SR-A以及蛋白激酶PKC-θ的表达水平。硝苯地平处理显著降低了ox-LDL处理的人巨噬细胞中的脂质蓄积和CD 36、SR-A和蛋白激酶C（PKC）-θ的表达。使用siRNA沉默PKC-θ也降低了这些细胞中CD 36和SR-A的表达。我们的研究结果提示硝苯地平可能通过PKC-θ依赖性机制抑制CD 36/SR-A介导的巨噬细胞对ox-LDL的摄取，从而减少ox-LDL诱导的脂质沉积，从而抑制动脉粥样硬化。
Studies have shown that nifedipine, an anti-hypertensive drug, protects against atherosclerotic progression, but the underlying mechanisms remain elusive. Oxidized low-density lipoprotein (ox-LDL) is critically implicated in macrophage lipid deposition seen in atherosclerosis. In this study, we examined the effects of nifedipine on some ox-LDL-associated changes in human blood-derived macrophages. We isolated monocytes from normal human blood and differentiated them into macrophages. We then treated these human macrophages with ox-LDL and/or nifedipine, and examined lipid accumulation and expression levels of two scavenge receptors CD36 and SR-A as well as a protein kinase PKC-θ. Nifedipine treatment substantially reduced lipid accumulation and the expression of CD36, SR-A, and protein kinase C (PKC)-θ in human macrophages treated with ox-LDL. Silencing of PKC-θ using siRNA also reduced the expression of CD36 and SR-A in these cells. Our results thus suggest that nifedipine may inhibit atherosclerosis by reducing ox-LDL-induced lipid deposition through suppression of the CD36/SR-A-mediated uptake of ox-LDL by macrophages via a PKC-θ-dependent mechanism.