Hypercholesterolemia and Lymphatic Defects: The Chicken or the Egg?
Hypercholesterolemia and Lymphatic Defects: The Chicken or the Egg?
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DOI：
10.3389/fcvm.2021.701229
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发表时间：
2021
影响因子：
3.6
通讯作者：
Miyazaki A
中科院分区：
文献类型：
--
作者：
Miyazaki T;Miyazaki A
淋巴管是维持组织液体平衡、运输免疫细胞和运输膳食脂质所必需的。越来越多的证据表明，在高胆固醇血症的情况下，淋巴功能受到限制，这与冠状动脉和其他大动脉的动脉粥样硬化发展密切相关。事实上，chy突变导致淋巴系统消融以及淋巴管生成因子（包括血管内皮生长因子- c和-D）的耗竭会扰乱小鼠的脂蛋白组成，从而增加高胆固醇血症。一些研究报道，动脉周围的微淋巴管被动脉粥样硬化源性淋巴管生成因子所吸引，从而促进淋巴管侵入动脉粥样硬化病变的内膜，从而改变免疫细胞的运输。与淋巴系统的脂质调节和免疫调节作用相反，高胆固醇血症条件下淋巴管生成的关键驱动因素和淋巴损伤的细节尚未完全阐明。有趣的是，降低胆固醇的试验可以预防小鼠淋巴引流的高胆固醇血症；然而，高胆固醇血症和淋巴缺陷之间的因果关系仍然难以捉摸。本文综述了异常淋巴管生成和淋巴胆固醇转运在高胆固醇血症性动脉粥样硬化中的作用。讨论了高胆固醇血症与淋巴损伤之间的因果关系以及目前在这一领域的研究进展。
Lymphatic vessels are necessary for maintaining tissue fluid balance, trafficking of immune cells, and transport of dietary lipids. Growing evidence suggest that lymphatic functions are limited under hypercholesterolemic conditions, which is closely related to atherosclerotic development involving the coronary and other large arteries. Indeed, ablation of lymphatic systems by Chy-mutation as well as depletion of lymphangiogenic factors, including vascular endothelial growth factor-C and -D, in mice perturbs lipoprotein composition to augment hypercholesterolemia. Several investigations have reported that periarterial microlymphatics were attracted by atheroma-derived lymphangiogenic factors, which facilitated lymphatic invasion into the intima of atherosclerotic lesions, thereby modifying immune cell trafficking. In contrast to the lipomodulatory and immunomodulatory roles of the lymphatic systems, the critical drivers of lymphangiogenesis and the details of lymphatic insults under hypercholesterolemic conditions have not been fully elucidated. Interestingly, cholesterol-lowering trials enable hypercholesterolemic prevention of lymphatic drainage in mice; however, a causal relationship between hypercholesterolemia and lymphatic defects remains elusive. In this review, the contribution of aberrant lymphangiogenesis and lymphatic cholesterol transport to hypercholesterolemic atherosclerosis was highlighted. The causal relationship between hypercholesterolemia and lymphatic insults as well as the current achievements in the field were discussed.
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影响因子：
15.9
作者：
Martel, Catherine;Li, Wenjun;Randolph, Gwendalyn J.
通讯作者：
Randolph, Gwendalyn J.
影响因子：
4.3
作者：
通讯作者：
--
DOI：
10.1152/ajpregu.1998.275.5.r1543
发表时间：
1998-11-01
影响因子：
2.8
作者：
Abu-Amarah, I;Ajikobi, DO;Salevsky, FC
通讯作者：
Salevsky, FC
影响因子：
11.2
作者：
Lahdenranta J;Hagendoorn J;Padera TP;Hoshida T;Nelson G;Kashiwagi S;Jain RK;Fukumura D
通讯作者：
Fukumura D
影响因子：
4.8
作者：
Kajiya, Kentaro;Huggenberger, Reto;Detmar, Michael
通讯作者：
Detmar, Michael