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内皮脂肪酶通过增加β-VLDL 的代谢分解发挥抗动脉粥样硬化作用。

Endothelial Lipase Exerts its Anti-Atherogenic Effect through Increased Catabolism of β-VLDLs.

机构信息

Department of Molecular Pathology, Faculty of Medicine, Graduate School of Interdisciplinary Research, University of Yamanashi.

Department of Pharmacology, College of Pharmacy, Shaanxi University of Chinese Medicine.

出版信息

J Atheroscler Thromb. 2021 Feb 1;28(2):157-168. doi: 10.5551/jat.55244. Epub 2020 May 23.

DOI:10.5551/jat.55244
PMID:32448826
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7957034/
Abstract

AIM

Endothelial lipase (EL) plays an important role in lipoprotein metabolism. Our recent study showed that increased hepatic expression of EL attenuates diet-induced hypercholesterolemia, thus subsequently reducing atherosclerosis in transgenic (Tg) rabbits. However, it is yet to be determined whether increased EL activity itself per se is anti-atherogenic or whether the anti-atherogenic effect of EL is exclusively dependent on its lipid-lowering effect.

METHODS

To determine the mechanisms underlying EL-mediated anti-atherogenic effect, we fed Tg and non-Tg rabbits diets containing different amounts of cholesterol to make their plasma cholesterol levels similarly high. Sixteen weeks later, we examined their lipoprotein profiles and compared their susceptibility to atherosclerosis.

RESULTS

With Tg and non-Tg rabbits having hypercholesterolemia, the plasma lipids and lipoprotein profiles were observed to be similar, while pathological examinations revealed that lesion areas of both aortic and coronary atherosclerosis of Tg rabbits were not significantly different from non-Tg rabbits. Moreover, Tg rabbits exhibited faster clearance of DiI-labeled β-VLDLs than non-Tg rabbits.

CONCLUSION

The results of our study suggest that the enhancement of β-VLDL catabolism is the major mechanism for atheroprotective effects of EL in Tg rabbits.

摘要

目的

内皮脂肪酶（EL）在脂蛋白代谢中起着重要作用。我们最近的研究表明，肝内 EL 表达增加可减轻饮食诱导的高胆固醇血症，从而减少转基因（Tg）兔的动脉粥样硬化。然而，尚不确定 EL 活性本身是否具有抗动脉粥样硬化作用，还是 EL 的抗动脉粥样硬化作用仅取决于其降脂作用。

方法

为了确定 EL 介导的抗动脉粥样硬化作用的机制，我们用含有不同胆固醇量的饮食喂养 Tg 和非 Tg 兔，使它们的血浆胆固醇水平相似。16 周后，我们检查了它们的脂蛋白谱，并比较了它们发生动脉粥样硬化的易感性。

结果

当 Tg 和非 Tg 兔出现高胆固醇血症时，血浆脂质和脂蛋白谱观察到相似，而病理检查显示 Tg 兔的主动脉和冠状动脉粥样硬化病变面积与非 Tg 兔无明显差异。此外，Tg 兔清除 DiI 标记的β-VLDL 的速度比非 Tg 兔快。

结论

我们的研究结果表明，β-VLDL 代谢的增强是 EL 在 Tg 兔中发挥抗动脉粥样硬化作用的主要机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/b26a75e56fca/jat-28-157-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/19f1e553dc10/jat-28-157-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/774dd2049e2d/jat-28-157-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/e72819bb734c/jat-28-157-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/9931ff39a3e1/jat-28-157-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/b6bc29984c99/jat-28-157-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/de2036fe385e/jat-28-157-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/8751ba04c399/jat-28-157-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/80be6429dcce/jat-28-157-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/b26a75e56fca/jat-28-157-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/19f1e553dc10/jat-28-157-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/774dd2049e2d/jat-28-157-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/e72819bb734c/jat-28-157-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/9931ff39a3e1/jat-28-157-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/b6bc29984c99/jat-28-157-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/de2036fe385e/jat-28-157-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/8751ba04c399/jat-28-157-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/80be6429dcce/jat-28-157-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab33/7957034/b26a75e56fca/jat-28-157-g009.jpg

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