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首页> 外文期刊>American Journal of Physiology >ApoE-mediated cholesterol efflux from macrophages: separation of autocrine and paracrine effects.
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ApoE-mediated cholesterol efflux from macrophages: separation of autocrine and paracrine effects.

机译：ApoE介导的巨噬细胞胆固醇流出：自分泌和旁分泌作用的分离。

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摘要

Macrophages in the vessel wall secrete high levels of apolipoprotein E (apoE). Cholesterol efflux from macrophages to apoE has been shown to decrease foam cell formation and prevent atherosclerosis. An apoE molecule can mediate cholesterol efflux from the macrophage that originally secreted it (autocrine effect) or from surrounding macrophages (paracrine effect). Traditional methodologies have not been able to separate these serial effects. The novel methodology presented here was developed to separate autocrine and paracrine effects by using a simple mathematical model to interpret the effects of dilution on apoE-mediated cholesterol efflux. Our results show that, at very dilute concentrations, the paracrine effect of apoE is not evident and the autocrine effect becomes the dominant mediator of efflux. However, at saturating concentrations, paracrine apoE causes 80-90% of the apoE-mediated cholesterol efflux, whereas autocrine apoE is responsible for the remaining 10-20%. These results suggest that the relative importance of autocrine and paracrine apoE depends on the size of the local distribution volume, a factor not considered in previous in vitro studies of apoE function. Furthermore, autocrine effects of apoE could be critical in the prevention of foam cell formation in vivo. This novel methodology may be applicable to other types of mixed autocrine/paracrine systems, such as signal transduction systems.
机译：血管壁中的巨噬细胞分泌高水平的载脂蛋白E（apoE）。从巨噬细胞到apoE的胆固醇外流可减少泡沫细胞的形成并预防动脉粥样硬化。 apoE分子可以介导胆固醇从最初分泌它的巨噬细胞（自分泌作用）或周围的巨噬细胞（旁分泌作用）流出。传统方法无法分离出这些串行影响。通过使用简单的数学模型来解释稀释对apoE介导的胆固醇外流的影响，开发了此处介绍的新颖方法来分离自分泌和旁分泌的作用。我们的结果表明，在非常稀的浓度下，apoE的旁分泌作用并不明显，自分泌作用成为流出的主要介体。但是，在饱和浓度下，旁分泌apoE引起apoE介导的胆固醇外流的80-90％，而自分泌apoE负责其余10-20％。这些结果表明自分泌和旁分泌apoE的相对重要性取决于局部分布体积的大小，这是先前在apoE功能的体外研究中未考虑的因素。此外，apoE的自分泌作用对于预防体内泡沫细胞的形成可能至关重要。这种新颖的方法可以适用于其他类型的混合自分泌/旁分泌系统，例如信号转导系统。

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