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.
| Original language | English (US) |
|---|---|
| Journal | Cell Metabolism |
| DOIs | |
| State | E-pub ahead of print - Oct 11 2018 |
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Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis. / 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.
In: Cell Metabolism, 11.10.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis
AU - Soberanes, Saul
AU - Misharin, Alexander V
AU - Jairaman, Amit
AU - Morales-Nebreda, Luisa
AU - McQuattie-Pimentel, Alexandra C
AU - Cho, Takugo
AU - Hamanaka, Robert B
AU - Meliton, Angelo Y
AU - Reyfman, Paul A
AU - Walter, James M
AU - Chen, Ching-I
AU - Chi, Monica
AU - Chiu, Stephen
AU - Gonzalez-Gonzalez, Francisco J
AU - Antalek, Matthew
AU - Abdala-Valencia, Hiam
AU - Chiarella, Sergio E
AU - Sun, Kaitlyn A
AU - Woods, Parker S
AU - Ghio, Andrew J
AU - Jain, Manu
AU - Perlman, Harris
AU - Ridge, Karen M
AU - Morimoto, Richard I
AU - Sznajder, Jacob I
AU - Balch, William E
AU - Bhorade, Sangeeta M
AU - Bharat, Ankit
AU - Prakriya, Murali
AU - Chandel, Navdeep S
AU - Mutlu, Gökhan M
AU - Budinger, G R Scott
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2018/10/11
Y1 - 2018/10/11
N2 - 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.
AB - 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.
U2 - 10.1016/j.cmet.2018.09.019
DO - 10.1016/j.cmet.2018.09.019
M3 - Article
C2 - 30318339
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
ER -