Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macrophages

MARCHINI, TIMOTEO; WOLF, DENNIS; ANTO MICHEL, NATHALY; MAULER, MAXIMILIAN; DUFNER, BIANCA; HOPPE, NATALIE; BECKER, JESSICA; JACKEL, MARCUS; MAGNANI, NATALIA; DUERSCHMIED, DANIEL ; TASAT, DEBORAH; ALVAREZ, SILVIA; REINÖHL, JOCHEN ; VON ZUR MUHLEN,CONSTANTIN ; IDZKO, MARCO; BODE, CHRISTOPH; HILGERNDORF, INGO; EVELSON, PABLO; ZIRLIK, ANDREAS

BASIC RESEARCH IN CARDIOLOGY

DR DIETRICH STEINKOPFF VERLAG

Año: 2016 vol. 111 p. 1 - 9

0300-8428

Clinical, but not experimental evidence has suggested that air pollution particulate matter (PM) aggravates myocardial infarction (MI). Here, we aimed todescribe 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 TNFa, 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 bereversed by neutralizing anti-TNF-a treatment. We identified alveolar macrophages as the primary source of elevated cytokine production after PM exposure. Accordingly, in vivo depletion of alveolar macrophages by intranasalclodronate 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 alveolarmacrophages 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 cardiovasculardisease.