Hypertensive Stimuli Indirectly Stimulate Lymphangiogenesis through Immune Cell Secreted Factors.
Hypertensive Stimuli Indirectly Stimulate Lymphangiogenesis through Immune Cell Secreted Factors.
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(1)背景：先前有报道称，在多种高血压小鼠模型（HTN）中，肾免疫细胞和淋巴管（LV）密度增加。然而，间质水平的HTN刺激如血管紧张素II、盐或不对称二甲基精氨酸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刺激直接增加了淋巴内皮细胞（LEC）的增殖、LEC三维基质的侵袭和血管形成以及小鼠系膜lv的发芽。(2)方法：人LECs （hLECs）和小鼠LECs （mLECs）分别接受HTN刺激，小鼠外植的LVs分别接受相同的HTN刺激或HTN刺激条件介质。用HTN刺激小鼠脾细胞制备条件培养基。(3)结果：HTN刺激对hLEC和mLEC增殖无直接影响。HTN刺激hLECs增加了三维基质中管腔形成结构的数量和侵入距离（p < 0.05），但降低了平均管腔直径和每个侵入结构的细胞数量（p < 0.05）。来自HTN刺激处理的脾细胞的条件培养基显著减轻了小鼠中介膜lv的芽数（除盐外）和芽长减少，这是单独在HTN刺激中发现的。(4)结论：这些数据表明，HTN刺激通过HTN刺激处理的免疫细胞分泌因子间接阻止淋巴管生成减少。
(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.
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DOI：
10.1111/febs.15848
发表时间：
2022-05
期刊：
The FEBS journal
影响因子：
--
作者：
Gu X;Li SY;DeFalco T
通讯作者：
DeFalco T
影响因子：
6
作者：
Sun Z;Vattepu R;Zhang S
通讯作者：
Zhang S
影响因子：
4.8
作者：
Witzenbichler, B;Maisonpierre, PC;Isner, JM
通讯作者：
Isner, JM
影响因子：
1.7
作者：
Suarez-Martinez AD;Bierschenk S;Huang K;Kaplan D;Bayer CL;Meadows SM;Sperandio M;Murfee WL
通讯作者：
Murfee WL
影响因子：
3.2
作者：
Balasubbramanian, Dakshnapriya;Gelston, Catalina A. Lopez;Mitchell, Brett M.
通讯作者：
Mitchell, Brett M.