Impaired lung redox metabolism and cardiac mitochondrial function aggravates myocardial infarction in a mice model of chronic exposure to urban air pollution

MARCHINI, TIMOTEO; MAGNANI, NATALIA; GARCÉS, MARIANA; KELLY, JAZMIN; PAZ, MARIELA; CACERES, LOURDES; LASAGNI VITAR, ROMINA M.; CALABRO, VALERIA; CALTANA, LAURA; CONTIN, MARIO; REYNOSO, SOFÍA; LAGO, NESTOR; VICO, TAMARA; VANASCO, VIRGINIA; TRIPODI, VALERIA; ALVAREZ, SILVIA; GONZALEZ MAGLIO, DANIEL; BUCHHOLZ, BRUNO; BERRA, ALEJANDRO; GELPI, RICARDO; EVELSON, PABLO

Congreso virtual

Congreso; 20th Biennial Meeting of the Society for Free Radical Research International; 2021

Society for Free Radical Research International

The World Health Organization estimates that 91% of the world's population breathe low quality air. As a consequence, 7 million premature deaths occur every year due to air pollution exposure. From those, myocardial infarction (MI) accounts for 2.4 million deaths yearly, which represents 25% of the total global burden for this disease. Here, we aimed to understand some of the mechanisms by which urban air pollution exposure aggravates MI, focusing on the effects of airborne fine particulate matter (PM2.5) on lung redox metabolism and cardiac mitochondrial structure and function. Male 8-week-old BALB/c mice were exposed to urban air (UA, 278 μg PM2.5/m3) or filtered air (FA, 21 μg PM2.5/m3) in whole-body exposure chambers for up to 16 weeks. After 12 weeks, lung inflammatory cell recruitment was evidenced by histology in UA-exposed mice. Interestingly, impaired redox metabolism, characterized by increased lung GSSG content, decreased SOD activity, and increased NOX activation, preceded local inflammation in UA-exposed mice. Moreover, PM2.5 uptake and enhanced nitric oxide production was observed in alveolar macrophages from UA-exposed mice by electron microscopy and flow cytometry, respectively, together with increased proinflammatory cytokine levels (TNF-α and IL-6) in bronchoalveolar lavage and plasma. In the heart of UA-exposed mice, impaired tissue oxygen metabolism and altered mitochondrial ultrastructure and function were observed, by decreased active state respiration by48%, inner membrane depolarization, decreased ATP production by 17%, and enhanced H2O2 release by 39%. This scenario led to a significant increase in infarct size following in vivo myocardial ischemia/reperfusion injury, from 433% of the area at risk in FA-exposed mice to 664% in UA-exposed mice (p