?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, JAZMÍN; PAZ, MARIELA; CÁCERES, LOURDES; LASAGNI VITAR, ROMINA; CALABRÓ, VALERIA; CALTANA, LAURA; CONTIN MARIO; REYNOSO, SOFÍA; LAGO, NESTOR; VICO, TAMARA; VANASCO, VIRGINIA; TRIPODI, VALERIA; ALVAREZ, SILVIA; GONZÁLEZ MAGLIO, DANIEL; BUCHHOLZ, BRUNO; BERRA, ALEJANDRO; GELPI, RICARDO; EVELSON, PABLO

Congreso; 20th Biennial Meeting of SFRR International; 2021; 2021

TheWorld Health Organization estimates that 91% of the world´s population breathelow quality air. As a consequence, 7 million premature deaths occur every yeardue to air pollution exposure. From those, myocardial infarction (MI) accountsfor 2.4 million deaths yearly, which represents 25% of the total global burdenfor this disease. Here, we aimed to understand some of the mechanisms by whichurban air pollution exposure aggravates MI, focusing on the effects of airbornefine particulate matter (PM2.5) on lung redox metabolism and cardiacmitochondrial structure and function. Male 8-week-old BALB/c mice were exposedto urban air (UA, 27±8 µg PM2.5/m3) or filtered air (FA,2±1 µg PM2.5/m3) in whole-body exposure chambers for upto 16 weeks. After 12 weeks, lung inflammatory cell recruitment was evidencedby histology in UA-exposed mice. Interestingly, impaired redox metabolism,characterized by increased lung GSSG content, decreased SOD activity, andincreased NOX activation, preceded local inflammation in UA-exposed mice.Moreover, PM2.5 uptake and enhanced nitric oxide production wasobserved in alveolar macrophages from UA-exposed mice by electron microscopyand flow cytometry, respectively, together with increased proinflammatorycytokine levels (TNF-α and IL-6) in bronchoalveolar lavage and plasma. In theheart of UA-exposed mice, impaired tissue oxygen metabolism and alteredmitochondrial ultrastructure and function were observed, by decreased activestate respiration by 48%, inner membrane depolarization, decreased ATPproduction by 17%, and enhanced H2O2 release by 39%. Thisscenario led to a significant increase in infarct size following in vivo myocardial ischemia/reperfusioninjury, from 43±3% of the area at risk in FA-exposed mice to 66±4% inUA-exposed mice (p<0.01). Takentogether, our data unravel some of the pathways that might explain the adversehealth effects of air pollution exposure, and ultimately highlights theimportance of considering environmental factors in the development ofcardiovascular diseases.