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

MARCHINI, TIMOTEO; WOLF, DENNIS; ANTO MICHEL, NATHALY; MAULER, MAXIMILIAN; MAGNANI, NATALIA; TASAT, DEBORAH; ALVAREZ, SILVIA; HILGERNDORF, INGO; ZIRLIK, ANDREAS; EVELSON, PABLO

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clinica

Environmental particulate matter (PM) exposure is associated with increased cardiovascular morbidity and mortality rates, mainly due to myocardial infarction (MI) and its complications. We hypothesize that, following PM inhalation, alveolar macrophages orchestrate a local inflammatory response within the lung, which afterwards leads to systemic inflammation that affects disease progression. In the present work, we aimed to describe the mechanisms and consequences of PM exposure in an experimental model of MI. C57BL/6J mice were exposed to a PM surrogate (Residual Oil Fly Ash, ROFA) by intranasal installation, prior and after the permanent ligation of the left anterior descending coronary artery. Histological analysis of the myocardium at 7 days after MI showed increased infarct area and enhanced inflammatory cell recruitment in ROFA-exposed mice. Time-course evaluation of cell populations in infarcted tissue by flow cytometry revealed increased numbers of Ly6Chigh monocytes at day 3 after MI, as well as increased macrophages at day 7. Mechanistically, the ROFA exposure increased plasma TNF-α levels, induced the activation and expression of adhesion molecules in myeloid and endothelial cells, respectively, and enhanced leukocyte recruitment in models of sterile peritonitis and intravital microscopy. We identified alveolar macrophages as the primary source of elevated cytokine production after PM exposure. Accordingly, in vivo depletion of alveolar macrophages by an intranasal instillation of clodronate liposomes inhibited local and systemic ROFA-mediated cytokine secretion, as well as inflammatory cell recruitment in infarcted tissue. Taken together, our data demonstrate that the exposure to environmental PM worsens MI healing in mice. These findings provide a novel link between air pollution and inflammatory pathways, and emphasize the importance of environmental factors in cardiovascular disease.