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

MARCHINI T; WOLF D ; MAULER B; DUFNER B ; BECKERT J; JACKEL ; TASAT DR.; DUERSCHMIED ; BODE C; HILGENDORF I; ZIRLIK A ; MICHEL NA ; HOPPE N; MAGNIANI N; ALVAREZ S; EVELSON PA.

BASIC RESEARCH IN CARDIOLOGY

DR DIETRICH STEINKOPFF VERLAG

Año: 2016 vol. 111 p. 1 - 14

0300-8428

Clinical, but not experimental evidence hassuggested that air pollution particulate matter (PM)aggravates myocardial infarction (MI). Here, we aimed todescribe mechanisms and consequences of PM exposure inan experimental model of MI. C57BL/6J mice were challengedwith a PM surrogate (Residual Oil Fly Ash, ROFA)by intranasal installation before MI was induced by permanentligation of the left anterior descending coronaryartery. Histological analysis of the myocardium 7 daysafter MI demonstrated an increase in infarct area andenhanced inflammatory cell recruitment in ROFA-exposedmice. Mechanistically, ROFA exposure increased thelevels of the circulating pro-inflammatory cytokines TNFa,IL-6, and MCP-1, activated myeloid and endothelialcells, and enhanced leukocyte recruitment to the peritonealcavity and the vascular endothelium. Notably, these effectson endothelial cells and circulating leukocytes could bereversed by neutralizing anti-TNF-a treatment. We identifiedalveolar macrophages as the primary source of elevatedcytokine production after PM exposure. Accordingly,in vivo depletion of alveolar macrophages by intranasalclodronate attenuated inflammation and cell recruitment toinfarcted tissue of ROFA-exposed mice. Taken together,our data demonstrate that exposure to environmental PMinduces the release of inflammatory cytokines from alveolarmacrophages which directly worsens the course of MIin mice. These findings uncover a novel link between airpollution PM exposure and inflammatory pathways, highlightingthe importance of environmental factors in cardiovasculardisease.