Dataset Information

IRE1?/XBP1s branch of UPR links HIF1? activation to mediate ANGII-dependent endothelial dysfunction under particulate matter (PM) 2.5 exposure.

ABSTRACT: Short- and long-term exposure to particulate matter (PM) 2.5 instigates adverse health effect upon the cardiovascular (CV) system. Disclosing the molecular events by which PM2.5 evokes CV injuries is essential in developing effective risk-reduction strategy. Here we found that rats after intratracheally instillation with PM2.5 displayed increased circulating level of ANGII, the major bioactive peptide in renin-angiotensin-system (RAS), which resulted from the elevation of ANGII production in the vascular endothelium. Further investigations demonstrated that activation of IRE1?/XBP1s branch of unfolded protein response (UPR) was essential for augmented vascular ANGII signaling in response to PM2.5 exposure, whose effects strictly depends on the assembly of XBP1s/HIF1? transcriptional complex. Moreover, ablation of IRE1/XBP1/HIF?-dependent ACE/ANGII/AT1R axis activation inhibited oxidative stress and proinflammatory response in the vascular endothelial cells induced by PM2.5. Therefore, we conclude that PM2.5 exposure instigates endoplasmic reticulum instability, leading to the induction of IRE1?/XBP1s branch of UPR and links HIF1? transactivation to mediate ANGII-dependent endothelial dysfunction. Identifying novel therapeutic targets to alleviate ER stress and restore local RAS homeostasis in the endothelium may be helpful for the management of PM2.5-induced CV burden.

SUBMITTER: Xu X

PROVIDER: S-EPMC5647447 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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IRE1α/XBP1s branch of UPR links HIF1α activation to mediate ANGII-dependent endothelial dysfunction under particulate matter (PM) 2.5 exposure.

Xu Xiuduan X Qimuge Aodeng A Wang Hongli H Xing Chen C Gu Ye Y Liu Shasha S Xu Huan H Hu Meiru M Song Lun L

Scientific reports 20171018 1

Short- and long-term exposure to particulate matter (PM) 2.5 instigates adverse health effect upon the cardiovascular (CV) system. Disclosing the molecular events by which PM2.5 evokes CV injuries is essential in developing effective risk-reduction strategy. Here we found that rats after intratracheally instillation with PM2.5 displayed increased circulating level of ANGII, the major bioactive peptide in renin-angiotensin-system (RAS), which resulted from the elevation of ANGII production in the ...[more]

PMID: 29044123

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Dataset Information

IRE1?/XBP1s branch of UPR links HIF1? activation to mediate ANGII-dependent endothelial dysfunction under particulate matter (PM) 2.5 exposure.

Publications

IRE1α/XBP1s branch of UPR links HIF1α activation to mediate ANGII-dependent endothelial dysfunction under particulate matter (PM) 2.5 exposure.

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