Mechanism of YY1 mediating autophagy dependent ferroptosis in PM2.5 induced cardiac fibrosis. (February 2023)

• Record Type: Journal Article
• Authors: Hu, Huaifang; Li, Lipeng; Zhang, Huaxing; Zhang, Yaling; Liu, Qingping; Chen, Meiyu; Ning, Jie; Pang, Yaxian; Hu, Wentao; Niu, Yujie; Zhang, Rong
• Is Part Of: Chemosphere. Volume 315(2023)
• Publication Date: 2023-02
• Subjects: Yin Yang 1 -- NCOA4 -- ECM -- Cardiac function -- Fine particulate matter; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2023.137749
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Epidemiological studies have demonstrated strong associations between exposure to ambient fine particulate matter (PM2.5) and cardiac disease. To investigate the potential mechanism of cardiac fibrosis induced by PM2.5, we established PM2.5 exposure models in vivo and in vitro, and then cardiac fibrosis was evaluated. The ferroptosis and ferritinophagy was detected to characterize the effects of PM2.5 exposure. The results indicated that PM2.5 exposure could induce cardiac fibrosis in mice. YY1 was induced by PM2.5 exposure and then increased NCOA4, a cargo receptor for ferritinophagy, which interacted with FHC and promoted the transport of ferritin to the autophagosome for degradation. The release of large amounts of free iron from ferritinophagy led to lipid peroxidation directly via the Fenton reaction, thereby triggering ferroptosis. Moreover, siNCOA4 could partly restore the FHC protein level in HL-1 cells and inhibit the occurrence of downstream ferroptosis. Functionally, NCOA4 knockdown inhibited ferroptosis and alleviated HL-1 cell death induced by PM2.5. Ferroptosis inhibitor (Ferrostatin-1) could reverse the promoting effect of ferritinophagy mediated ferroptosis on cardiac fibrosis induced by PM2.5 exposure in mice. Our study indicated that PM2.5 induced cardiac fibrosis through YY1 regulating ferritinophagy-dependent ferroptosis. Graphical abstract: Image 1 Highlights: Long-term exposure to PM2.5 induced cardiac fibrosis through ferroptosis activation. PM2.5-induced cardiac fibrosis was associated with the increase of ferritinophagy. YY1 regulated the ferritinophagy pathway by recognizing NCOA4.