College of Medicine, Texas A&M University, Bryan, TX 77807, USA.
Cells. 2022 Jul 7;11(14):2139. doi: 10.3390/cells11142139.
(1) Background: Renal immune cells and lymphatic vessel (LV) density have been reported previously to be increased in multiple mouse models of hypertension (HTN). However, whether interstitial levels of HTN stimuli such as angiotensin II, salt, or asymmetric dimethylarginine have a direct or indirect effect on lymphangiogenesis is unknown. We hypothesized that these 3 HTN stimuli directly increase lymphatic endothelial cell (LEC) proliferation, LEC 3-D matrix invasion and vessel formation, and sprouting of mouse mesometrial LVs. (2) Methods: Human LECs (hLECs) and mouse LECs (mLECs) were treated with HTN stimuli while explanted mouse mesometrial LVs were treated with either the same HTN stimuli or with HTN stimuli-conditioned media. Conditioned media was prepared by treating murine splenocytes with HTN stimuli. (3) Results: HTN stimuli had no direct effect on hLEC or mLEC proliferation. Treatment of hLECs with HTN stimuli increased the number of lumen-forming structures and invasion distance (both p < 0.05) in the 3-D matrix but decreased the average lumen diameter and the number of cells per invading structure (both p < 0.05). Conditioned media from HTN-stimuli-treated splenocytes significantly attenuated the decrease in sprout number (aside from salt) and sprout length of mouse mesometrial LVs that is found in the HTN stimuli alone. (4) Conclusions: These data indicate that HTN stimuli indirectly prevent a decrease in lymphangiogenesis through secreted factors from HTN-stimuli-treated immune cells.
(1) 背景：先前已有研究报道，在多种高血压（HTN）小鼠模型中，肾脏免疫细胞和淋巴管（LV）密度增加。然而，HTN 刺激物（如血管紧张素 II、盐或不对称二甲基精氨酸）的间质水平是否对淋巴管生成有直接或间接的影响尚不清楚。我们假设这 3 种 HTN 刺激物直接增加淋巴管内皮细胞（LEC）增殖、LEC 三维基质侵袭和血管形成以及鼠中肾系膜 LV 的出芽。(2) 方法：将 HTN 刺激物用于培养人淋巴管内皮细胞（hLEC）和鼠淋巴管内皮细胞（mLEC），同时将相同的 HTN 刺激物或 HTN 刺激物条件培养基用于培养鼠中肾系膜 LV。条件培养基通过用 HTN 刺激物处理鼠脾细胞来制备。(3) 结果：HTN 刺激物对 hLEC 或 mLEC 的增殖没有直接影响。用 HTN 刺激物处理 hLEC 后，在三维基质中形成管腔结构的数量和侵袭距离增加（均 p < 0.05），但平均管腔直径和每个侵袭结构的细胞数量减少（均 p < 0.05）。来自 HTN 刺激物处理的脾细胞的条件培养基显著减弱了 HTN 刺激物单独处理时鼠中肾系膜 LV 的芽数（除盐以外）和芽长的减少。(4) 结论：这些数据表明，HTN 刺激物通过来自 HTN 刺激物处理的免疫细胞分泌的因子间接防止淋巴管生成减少。
