2. Academic Validation
  3. Mechanistic insight into airborne particulate matter PM10 as an environmental hazard for hemorrhagic stroke: Evidence from in vitro and in vivo studies

Mechanistic insight into airborne particulate matter PM10 as an environmental hazard for hemorrhagic stroke: Evidence from in vitro and in vivo studies

  • J Hazard Mater. 2024 Dec 5:480:136319. doi: 10.1016/j.jhazmat.2024.136319.
Chae Hwan Lee 1,  Moon Han Chang 2,  Young Ho Koh 2,  Seung Pil Pack 3,  Minseok Seo 4,  Hanvit Cha 5,  Jin Hyup Lee 6
Affiliations

Affiliations

  • 1 Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea; BK21 FOUR Research Group for Omics-based Bio-health in Food Industry, Korea University, Sejong, Republic of Korea; Biological Clock-based Anti-aging Convergence RLRC, Korea University, Sejong, Republic of Korea.
  • 2 Division of Brain Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju, Republic of Korea.
  • 3 Biological Clock-based Anti-aging Convergence RLRC, Korea University, Sejong, Republic of Korea; Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea.
  • 4 Biological Clock-based Anti-aging Convergence RLRC, Korea University, Sejong, Republic of Korea; Department of Computer and Information Science, Korea University, Sejong, Republic of Korea.
  • 5 Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea; Biological Clock-based Anti-aging Convergence RLRC, Korea University, Sejong, Republic of Korea. Electronic address: chahv@korea.ac.kr.
  • 6 Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea; BK21 FOUR Research Group for Omics-based Bio-health in Food Industry, Korea University, Sejong, Republic of Korea; Biological Clock-based Anti-aging Convergence RLRC, Korea University, Sejong, Republic of Korea; Institutes of Natural Sciences, Korea University, Sejong, Republic of Korea. Electronic address: jinhyuplee@korea.ac.kr.
PMID: 39488980 DOI: 10.1016/j.jhazmat.2024.136319
Abstract

Airborne particulate matter less than 10 µm in diameter (PM10) is recognized as a significant environmental risk factor for hemorrhagic stroke (HS), as evidenced by epidemiological studies that link PM10 with the heightened cerebrovascular mortality related to HS. Nonetheless, the molecular mechanisms underlying this association remain unknown. Cerebral aneurysm (CA), an etiological factor of HS, is characterized by a bulge resulting from the abnormal loss of the muscular layer of a cerebral artery, comprising brain vascular endothelial cell (BVEC) and vascular smooth muscle cell (VSMC). BVEC exhibiting an inflammatory phenotype is critical for VSMC death within the cerebrovasculature. Here, we elucidate a molecular mechanism by which PM10 augments necroptotic death of VSMC as a consequence of intercellular effects arising from FasL inflammatory cytokine, which is derived from BVEC. Notably, BVEC exposed to PM10 upregulates FasL through ATM-NF-κB signaling, in response to oxidative DNA damage. This genotoxic stress is attributed to pro-oxidant action of aluminum, the prevalent element in PM10. Furthermore, respiratory exposure to PM10 in mice precipitates early onset of CA development through necroptotic VSMC death in cerebral artery, by activating FasL expression in BVEC. In conclusion, this study provides molecular evidence establishing a direct association between PM10 pollution and an elevated risk of stroke, particularly HS.

Keywords

Air pollution; Aluminum; Cerebrovascular disease; FasL; Necroptosis.

Figures
Products