PM2.5 increases mouse blood pressure by activating toll-like receptor 3.
PM2.5 increases mouse blood pressure by activating toll-like receptor 3.
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DOI：
10.1016/j.ecoenv.2022.113368
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发表时间：
2022-03
影响因子：
6.8
通讯作者：
Jinna Zhang;Rucheng Chen;Guoqing Zhang;Yixuan Wang;Jing Peng;Renjie Hu;Ran Li;Weijia Gu;Lu Zhang;Qinghua Sun;Cuiqing Liu
中科院分区：
文献类型：
--
作者：
Jinna Zhang;Rucheng Chen;Guoqing Zhang;Yixuan Wang;Jing Peng;Renjie Hu;Ran Li;Weijia Gu;Lu Zhang;Qinghua Sun;Cuiqing Liu
背景与目的大量文献表明细颗粒物（PM2.5）暴露与血压升高有关。血管功能障碍是高血压等心血管疾病的起始。本论文旨在探讨Toll样受体3（TLR 3）在PM2.5引起的血压升高中的作用。方法将C57 BL/6和TLR 3缺陷（TLR 3-/-）雄性小鼠随机分为过滤空气室和真实环境吸入高浓度PM2.5室。使用无创血压记录评估血压。安乐死后，分离肠系膜动脉和小肠系膜动脉（SMA），并使用钢丝肌描记器测量血管张力。分离白细胞以使用流式细胞术评估髓源性抑制细胞。进行siRNA转染以沉默与PM2.5孵育的人血管内皮细胞中的TLR 3表达。炎症，粘附分子和氧化应激的基因表达水平进行了评估，通过定量PCR.ResultsExposure to PM2. 5 increased mouse BP，and TLR 3 deficiency protected against PM2. 5sure-induced BP increase.此外，TLR 3-/-小鼠的动脉和SMA中的血管功能损伤受到抑制。TLR 3-/-小鼠的细胞间粘附分子-1（ICAM-1）减弱，同时伴有炎症和氧化基因的抑制，如F4/80、白细胞介素-6、白细胞介素-1 β和NADPH氧化酶4。在体外实验中，TLR 3沉默可抑制PM2. 5引起的炎症、氧化应激和ICAM-1基因mRNA表达的增加。结论PM2. 5通过激活TLR 3而导致血压升高，并损害血管功能。
Background and aimsPlenty of literature has documented that fine particulate matter (PM2.5) exposure is related to blood pressure (BP) elevation. Vascular dysfunction is the initiation of cardiovascular diseases, such as hypertension. This thesis set out to assess the role of Toll-like receptor 3 (TLR3) in the increase in BP induced by PM2.5.MethodsC57BL/6 and TLR3 deficient (TLR3-/-) male mice were randomly allocated to filtered air chamber or real-world inhaled concentrated PM2.5chamber. BP was evaluated using non-invasive BP recordings. After euthanasia, the aortas and small mesenteric arteries (SMAs) were isolated, and vascular tone was measured using a wire myograph. Leucocytes were detached to assess myeloid-derived suppressor cells using flow cytometry. siRNA transfection was performed to silence TLR3 expression in the human vascular endothelial cells incubated with PM2.5. The gene expression levels of inflammation, adhesion molecules, and oxidative stress in the aortas were assessed by quantitative PCR.ResultsExposure to PM2.5increased mouse BP, and TLR3 deficiency protected against PM2.5exposure-induced BP increase. Additionally, the injury of vascular function in the aortas and SMAs was inhibited in TLR3-/-mice. The intercellular adhesion molecule-1 (ICAM-1) was attenuated in TLR3-/-mice, accompanied by the inhibition of inflammatory and oxidized genes of the aortas, such as F4/80, interleukin-6, interleukin-1 beta, and NADPH oxidase 4. In vitro, the enhanced mRNA expression of genes encoding inflammation, oxidative stress, and ICAM-1 by PM2.5was inhibited by TLR3 silence as well.ConclusionsPM2.5exposure increased BP via TLR3 activation and impaired vascular function.