5th Medical Department, University Hospital Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Department of Obstetrics and Gynecology, LMU University Hospital, LMU Munich, Munich, Germany.
Sci Rep. 2023 Sep 27;13(1):16159. doi: 10.1038/s41598-023-43142-6.
Systemic inflammation affects the whole vasculature, yet whether arterial and venous endothelial cells differ in their abilities to mediate inflammation and to return to homeostasis after an inflammatory stimulus has not been addressed thoroughly. We assessed gene-expression profiles in isolated endothelial cells from human umbilical arteries (HUAEC) or veins (HUVEC) under basal conditions, after TNF-α stimulation and various time points after TNF-α removal to allow reinstatement of homeostasis. TNF-α regulates the expression of different sets of transcripts that are significantly changed only in HUAEC, only in HUVEC or changed in both. We identified three types of gene regulation, i.e. genes that were significantly regulated after 24 h of TNF-α stimulation but no longer when TNF-α was removed (homeostatic regulation), genes that maintained significantly regulated after TNF-α removal (not homeostatic regulation) and genes that were only significantly regulated when TNF-α was removed (post-regulation). HUAEC and HUVEC quantitatively differed in these types of gene regulation, with relatively more genes being post-regulated in HUAEC. In conclusion our data demonstrate that HUAEC and HUVEC respond intrinsically different to an inflammatory insult. Whether this holds true for all endothelial cells and its relevance for inflammatory insults in different organs during systemic inflammation warrants further studies.
系统性炎症会影响整个血管系统，但动脉和静脉内皮细胞在介导炎症以及在炎症刺激后恢复到体内平衡的能力方面是否存在差异，尚未得到充分研究。我们评估了在基础条件下、在 TNF-α 刺激后以及在 TNF-α 去除后的不同时间点从人脐带动脉内皮细胞（HUAEC）或静脉内皮细胞（HUVEC）中分离的内皮细胞的基因表达谱，以允许恢复体内平衡。TNF-α 调节不同转录本集的表达，这些转录本仅在 HUAEC 中显著变化，仅在 HUVEC 中显著变化，或在两者中均显著变化。我们确定了三种基因调控类型，即：在 TNF-α 刺激 24 小时后显著调控但在去除 TNF-α 后不再调控的基因（稳态调控）、在去除 TNF-α 后仍显著调控的基因（非稳态调控）和仅在去除 TNF-α 后显著调控的基因（后调控）。HUAEC 和 HUVEC 在这些类型的基因调控中存在定量差异，HUAEC 中后调控基因相对较多。总之，我们的数据表明，HUAEC 和 HUVEC 对炎症刺激的反应本质上不同。这种情况是否适用于所有内皮细胞，以及它在全身炎症期间对不同器官炎症刺激的相关性，值得进一步研究。
