尼古丁可能通过……改变内皮炎症和细胞黏附。

Nicotine Potentially Alters Endothelial Inflammation and Cell Adhesion via .

作者信息

Braß Sönke Maximilian, Mazrekaj Agnesa, Mulorz Joscha, Ibing Wiebke, Krott Kim-Jürgen, Takeuchi Kiku, Cappallo Melanie, Liu Hsiang-Han, Elvers Margitta, Schelzig Hubert, Wagenhäuser Markus Udo

机构信息

Clinic for Vascular and Endovascular Surgery, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University, 40225 Duesseldorf, Germany.

Clinic for Cardiac Surgery, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University, 40225 Duesseldorf, Germany.

出版信息

J Cardiovasc Dev Dis. 2023 Dec 23;11(1):6. doi: 10.3390/jcdd11010006.

DOI:10.3390/jcdd11010006

PMID:38248876

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10816207/

Abstract

BACKGROUND

The endothelial cell layer is essential for the maintenance of various blood vessel functions. Major risk factors for endothelial dysfunction that contribute to aortic pathologies such as abdominal aortic aneurysm (AAA) and aortic dissection (AD) include smoking tobacco cigarettes and hypertension. This study explores the effects of nicotine (Nic) and angiotensin II (Ang II) on human aortic endothelial cells (HAoECs) at a transcriptional level.

METHODS

HAoECs were exposed to 100 nM Nic and/or 100 nM Ang II. RNA sequencing (RNA-Seq) was performed to identify regulated genes following exposure. Results were validated applying RT-qPCR. GeneMANIA was used to perform in silico analysis aiming to identify potential downstream interacting genes in inflammatory, cell-adhesion, endothelial cell proliferation, and coagulation pathways.

RESULTS

RNA-Seq identified (Galectin-9) as being potentially regulated following Nic exposure, while subsequent RT-qPCR experiments confirmed the transcriptional regulation ( < 0.05). Subsequent in silico analysis identified potential candidate genes for interacting with in different gene sets. Of the top 100 genes potentially interacting with , 18 were inflammatory response genes, 28 were involved in cell adhesion, 2 in cell proliferation, and 6 in coagulation.

CONCLUSION

Nic exposure of HAoECs causes a significant increase in at a transcriptional level. itself may serve as key regulator for essential endothelial cell processes via interfering with various signaling pathways and may thus represent a potentially novel target in the pathogenesis of aortic pathologies.

摘要

背景

内皮细胞层对于维持各种血管功能至关重要。导致主动脉病变如腹主动脉瘤（AAA）和主动脉夹层（AD）的内皮功能障碍的主要危险因素包括吸烟和高血压。本研究在转录水平上探讨尼古丁（Nic）和血管紧张素II（Ang II）对人主动脉内皮细胞（HAoECs）的影响。

方法

将HAoECs暴露于100 nM Nic和/或100 nM Ang II。进行RNA测序（RNA-Seq）以鉴定暴露后受调控的基因。应用RT-qPCR对结果进行验证。使用GeneMANIA进行计算机分析，旨在鉴定炎症、细胞粘附、内皮细胞增殖和凝血途径中潜在的下游相互作用基因。

结果

RNA-Seq鉴定出半乳糖凝集素-9（Galectin-9）在Nic暴露后可能受到调控，随后的RT-qPCR实验证实了转录调控（P<0.05）。随后的计算机分析确定了在不同基因集中与Galectin-9相互作用的潜在候选基因。在与Galectin-9潜在相互作用的前100个基因中，18个是炎症反应基因，28个参与细胞粘附，2个参与细胞增殖，6个参与凝血。