Title: Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis.
Authors: Soberanes, Saul; Misharin, Alexander V; Jairaman, Amit; Morales-Nebreda, Luisa; McQuattie-Pimentel, Alexandra C; Cho, Takugo; Hamanaka, Robert B; Meliton, Angelo Y; Reyfman, Paul A; Walter, James M; Chen, Ching-I; Chi, Monica; Chiu, Stephen; Gonzalez-Gonzalez, Francisco J; Antalek, Matthew; Abdala-Valencia, Hiam; Chiarella, Sergio E; Sun, Kaitlyn A; Woods, Parker S; Ghio, Andrew J; Jain, Manu; Perlman, Harris; Ridge, Karen M; Morimoto, Richard I; Sznajder, Jacob I; Balch, William E; Bhorade, Sangeeta M; Bharat, Ankit; Prakriya, Murali; Chandel, Navdeep S; Mutlu, Gökhan M; Budinger, G R Scott
Published In Cell Metab, (2019 02 05)
Abstract: 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.
PubMed ID: 30318339
MeSH Terms: Air Pollution/adverse effects*; Animals; Cell Line; Cytokines/metabolism; Electron Transport; Humans; Interleukin-6/metabolism; Lung Diseases/drug therapy*; Macrophages, Alveolar/drug effects; Macrophages, Alveolar/metabolism*; Macrophages, Alveolar/pathology; Male; Metformin/pharmacology*; Mice; Mice, Inbred C57BL; Mitochondria/metabolism*; Particulate Matter/toxicity*; Reactive Oxygen Species/metabolism; Thrombosis/drug therapy*