title: Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macrophages.
abstract: Clinical, but not experimental evidence has suggested that air pollution particulate matter (PM) aggravates myocardial infarction (MI). Here, we aimed to describe mechanisms and consequences of PM exposure in an experimental model of MI. C57BL/6J mice were challenged with a PM surrogate (Residual Oil Fly Ash, ROFA) by intranasal installation before MI was induced by permanent ligation of the left anterior descending coronary artery. Histological analysis of the myocardium 7 days after MI demonstrated an increase in infarct area and enhanced inflammatory cell recruitment in ROFA-exposed mice. Mechanistically, ROFA exposure increased the levels of the circulating pro-inflammatory cytokines TNF-α, IL-6, and MCP-1, activated myeloid and endothelial cells, and enhanced leukocyte recruitment to the peritoneal cavity and the vascular endothelium. Notably, these effects on endothelial cells and circulating leukocytes could be reversed by neutralizing anti-TNF-α treatment. We identified alveolar macrophages as the primary source of elevated cytokine production after PM exposure. Accordingly, in vivo depletion of alveolar macrophages by intranasal clodronate attenuated inflammation and cell recruitment to infarcted tissue of ROFA-exposed mice. Taken together, our data demonstrate that exposure to environmental PM induces the release of inflammatory cytokines from alveolar macrophages which directly worsens the course of MI in mice. These findings uncover a novel link between air pollution PM exposure and inflammatory pathways, highlighting the importance of environmental factors in cardiovascular disease.
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.|Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Timoteo
authors.initials: T
authors.lastname: Marchini
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Wolf
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Nathaly Anto
authors.initials: NA
authors.lastname: Michel
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Mauler
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Dufner
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Hoppe
authors.affiliation: Department of Pneumology, University of Freiburg, Freiburg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Beckert
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Jäckel
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Magnani
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Duerschmied
authors.affiliation: School of Science and Technology, National University of General San Martín, Buenos Aires, Argentina.
authors.forename: Deborah
authors.initials: D
authors.lastname: Tasat
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Alvarez
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Reinöhl
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: von Zur Muhlen
authors.affiliation: Department of Pneumology, University of Freiburg, Freiburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Hilgendorf
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Evelson
authors.affiliation: Atherogenesis Research Group, Cardiology and Angiology I, University Heart Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany. andreas.zirlik@universitaets-herzzentrum.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zirlik
mesh_terms: D000818:Animals; D060729:Coal Ash / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005434:Flow Cytometry; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000276:immunology / Q000473:pathology*; D052638:Particulate Matter / Q000633:toxicity*
chemical_list: D060729:Coal Ash; D016207:Cytokines; D052638:Particulate Matter
keywords: Inflammation; Monocytes; Myocardial infarction; Particulate matter; ROFA