A continuous exposure to urban air pollution aggravates myocardial infarction in mice: the role of lung inflammation and impaired cardiac mitochondrial function

MARCHINI T; GARCÉS M; MAGNANI N; KELLY J; PAZ ML; LAGO N; MARGIOTTIELLO NAVARRO DR; CÁCERES L; VICO T; VANASCO V; ALVAREZ S; GONZÁLEZ MAGLIO DH; BERRA A; GELPI R; EVELSON P

Congreso; Reunión Conjunta SAIC SAI SAFIS 2018; 2018

Air pollution exposure is associated with increased mortality due to myocardial infarction (MI). It has been suggested that breathing polluted air leads to pulmonary and systemic inflammation, which might affect MI progression. To address this hypothesis, we evaluated the contribution of a continuous exposure to air pollution over experimental MI in mice, with particular focus over lung inflammation and cardiac mitochondrial function. Male eight-week-old BALB/c mice were exposed to filtered air (FA, control) or urban air (UA) inside wholebody inhalation chambers located in a highly populated area of Buenos Aires City for up to 16 weeks. After 8 weeks, mice breathing UA showed a 56% increase in total leucocyte count in bronchoalveolar lavage (BAL) samples (FA: 1.0±0.2 x105 cells, p<0.05), and a 104% increase in BAL protein concentration (FA: 0.30±0.04 mg/mL, p<0.05). Both BAL leucocyte count and protein concentration were still significantly increased after 12 weeks, together with a 3-fold increase in MCP-1 levels. Consistently, lung histology showed inflammatory leukocyte recruitment, edema, and thickening of the alveolar wall. Lung oxidative stress might precede inflammation, as increased phospholipid oxidation and decreased SOD activity were observed after 4 and 8 weeks, followed by a later increase in NADPH oxidase activity. Moreover, BAL analysis by flow cytometry showed increased alveolar macrophage activation and nitric oxide production in exposed mice after 12 weeks. In this group, a significant increase in TNF-α and IL-6 plasma levels were also observed. At this time point, UA exposure lead to a 53% increase in ischemia/reperfusion injury (FA: 43±4% risk area, p<0.01). Mechanistically, UA-exposed mice showed impaired cardiac mitochondrial function, characterized by decreased active state respiration, inner membrane depolarization, increased oxidants production, and decreased ATP production rate. Taken together, our data highlights the importance of considering environmental factors in the development of cardiovascular diseases inurban areas.