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

Abstract

Urban air pollution exposure is associated with increased mortality rates, mainly due to myocardial infarction (MI). In order to study the mechanisms underlying this observation, BALB/c mice were exposed to filtered air (FA, control) or urban air (UA) inside whole-body inhalation chambers located in Buenos Aires City, and subjected to MI after 12 weeks. Mice breathing UA showed increased BAL leucocyte count and protein concentration, together with increased TNF-α and MCP-1 levels. Consistently, lung histology showed thickening of the alveolar wall and inflammatory leukocyte recruitment. BAL analysis by flow cytometry showed enhanced alveolar macrophage activation in UA-exposed mice. In this group, a significant increase in plasma TNF-α was also observed. At this time point, UA exposure lead to enhanced ischemia/reperfusion injury. Mechanistically, UA-exposed mice showed impaired cardiac mitochondrial function, characterized by ultrastructural abnormalities, decreased active state respiration, inner membrane depolarization, increased O2●- and H2O2 production, and decreased ATP production rate. Our results indicate that a chronic exposure to UA induces a degree of lung inflammation that impairs mitochondrial function in distant organs, such as the heart, which worsens MI outcome. Taken together, our data highlights the importance of considering environmental factors in the development of cardiovascular diseases in urban areas.