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Publication : Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis.

First Author  Soberanes S Year  2019
Journal  Cell Metab Volume  29
Issue  2 Pages  335-347.e5
PubMed ID  30318339 Mgi Jnum  J:271762
Mgi Id  MGI:6282157 Doi  10.1016/j.cmet.2018.09.019
Citation  Soberanes S, et al. (2019) Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis. Cell Metab 29(2):335-347.e5
abstractText  Urban particulate matter air pollution induces the release of pro-inflammatory cytokines including interleukin-6 (IL-6) from alveolar macrophages, resulting in an increase in thrombosis. Here, we report that metformin provides protection in this murine model. Treatment of mice with metformin or exposure of murine or human alveolar macrophages to metformin prevented the particulate matter-induced generation of complex III mitochondrial reactive oxygen species, which were necessary for the opening of calcium release-activated channels (CRAC) and release of IL-6. Targeted genetic deletion of electron transport or CRAC channels in alveolar macrophages in mice prevented particulate matter-induced acceleration of arterial thrombosis. These findings suggest metformin as a potential therapy to prevent some of the premature deaths attributable to air pollution exposure worldwide.
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