Neurosurgery Research Group, Room B410b, Biomedicum 1, Haartmaninkatu 8, 00290, Helsinki, Finland.
Department of Neurosurgery, Helsinki University Hospital and University of Helsinki, Topeliuksenkatu 5, 00260, Helsinki, Finland.
Acta Neuropathol Commun. 2022 Sep 5;10(1):130. doi: 10.1186/s40478-022-01430-8.
Saccular intracranial aneurysm (sIA) rupture leads to subarachnoid haemorrhage and is preceded by chronic inflammation and atherosclerotic changes of the sIA wall. Increased lymphangiogenesis has been detected in atherosclerotic extracranial arteries and in abdominal aortic aneurysms, but the presence of lymphatic vessels in sIAs has remained unexplored. Here we studied the presence of lymphatic vessels in 36 intraoperatively resected sIAs (16 unruptured and 20 ruptured), using immunohistochemical and immunofluorescence stainings for lymphatic endothelial cell (LEC) markers. Of these LEC-markers, both extracellular and intracellular LYVE-1-, podoplanin-, VEGFR-3-, and Prox1-positive stainings were detected in 83%, 94%, 100%, and 72% of the 36 sIA walls, respectively. Lymphatic vessels were identified as ring-shaped structures positive for one or more of the LEC markers. Of the sIAs, 78% contained lymphatic vessels positive for at least one LEC marker. The presence of LECs and lymphatic vessels were associated with the number of CD68+ and CD163+ cells in the sIA walls, and with the expression of inflammation indicators such as serum amyloid A, myeloperoxidase, and cyclo-oxygenase 2, with the presence of a thrombus, and with the sIA wall rupture. Large areas of VEGFR-3 and α-smooth muscle actin (αSMA) double-positive cells were detected in medial parts of the sIA walls. Also, a few podoplanin and αSMA double-positive cells were discovered. In addition, LYVE-1 and CD68 double-positive cells were detected in the sIA walls and in the thrombus revealing that certain CD68+ macrophages are capable of expressing LEC markers. This study demonstrates for the first time the presence of lymphatic vessels in human sIA walls. Further studies are needed to understand the role of lymphatic vessels in the pathogenesis of sIA.
囊状颅内动脉瘤（sIA）破裂导致蛛网膜下腔出血，并伴有 sIA 壁的慢性炎症和动脉粥样硬化改变。在粥样硬化的颅外动脉和腹主动脉瘤中已经检测到淋巴管生成增加，但 sIA 中的淋巴管仍然没有被探索。在这里，我们使用淋巴管内皮细胞（LEC）标志物的免疫组织化学和免疫荧光染色，研究了 36 个术中切除的 sIA（16 个未破裂和 20 个破裂）中淋巴管的存在。在这些 LEC 标志物中，36 个 sIA 壁中的细胞外和细胞内 LYVE-1、podoplanin、VEGFR-3 和 Prox1 的阳性染色分别为 83%、94%、100%和 72%。淋巴管被鉴定为一种环形结构，对一个或多个 LEC 标志物呈阳性。在这些 sIA 中，78%的 sIA 壁含有至少一种 LEC 标志物阳性的淋巴管。LEC 的存在和淋巴管与 sIA 壁中 CD68+和 CD163+细胞的数量、炎症标志物如血清淀粉样蛋白 A、髓过氧化物酶和环氧化酶 2 的表达、血栓的存在以及 sIA 壁的破裂有关。在 sIA 壁的中膜部分检测到大量 VEGFR-3 和 α-平滑肌肌动蛋白（αSMA）双阳性细胞，还发现了一些 podoplanin 和 αSMA 双阳性细胞。此外，LYVE-1 和 CD68 双阳性细胞也在 sIA 壁和血栓中被检测到，这表明某些 CD68+巨噬细胞能够表达 LEC 标志物。这项研究首次证明了人类 sIA 壁中存在淋巴管。需要进一步的研究来了解淋巴管在 sIA 发病机制中的作用。
