Miyazaki Takuro, Miyazaki Akira
Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
Front Cardiovasc Med. 2021 Jun 23;8:701229. doi: 10.3389/fcvm.2021.701229. eCollection 2021.
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.
淋巴管对于维持组织液平衡、免疫细胞运输以及膳食脂质的转运至关重要。越来越多的证据表明，在高胆固醇血症条件下淋巴管功能受限，这与涉及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，在小鼠中通过Chy突变消融淋巴系统以及耗尽包括血管内皮生长因子-C和-D在内的淋巴管生成因子会扰乱脂蛋白组成，加剧高胆固醇血症。多项研究报告称，动脉周围微淋巴管被动脉粥样瘤衍生的淋巴管生成因子吸引，这促进了淋巴管侵入动脉粥样硬化病变的内膜，从而改变免疫细胞运输。与淋巴系统的脂质调节和免疫调节作用相反，淋巴管生成的关键驱动因素以及高胆固醇血症条件下淋巴损伤的细节尚未完全阐明。有趣的是，降胆固醇试验能够预防小鼠高胆固醇血症引起的淋巴引流；然而，高胆固醇血症与淋巴缺陷之间的因果关系仍然难以捉摸。在这篇综述中，异常淋巴管生成和淋巴胆固醇运输对高胆固醇血症性动脉粥样硬化的作用得到了强调。讨论了高胆固醇血症与淋巴损伤之间的因果关系以及该领域的当前成果。
