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

MARCHINI T; KELLY J; LASAGNI VITAR RM; CONTIN M; VICO T; ALVAREZ S; BERRA A; GARCÉS M; CÁCERES L; CALTANA L; LAGO N; TRIPODI V; BUCHHOLZ BRUNO; PABLO, EVELSON; MAGNANI N; PAZ ML ; CALABRÓ V; REYNOSO S; VANASCO V; GONZÁLEZ MAGLIO DH.; GELPI RJ

Congreso; SFRRI 2021; 2021

SFRRI

The World Health Organization estimates that 91% of the world's population breathe lowquality air. As a consequence, 7 million premature deaths occur every year due to airpollution exposure. From those, myocardial infarction (MI) accounts for 2.4 million deathsyearly, which represents 25% of the total global burden for this disease. Here, we aimed tounderstand some of the mechanisms by which urban air pollution exposure aggravates MI,focusing on the effects of airborne fine particulate matter (PM 2.5 ) on lung redox metabolismand cardiac mitochondrial structure and function. Male 8-week-old BALB/c mice wereexposed to urban air (UA, 27±8 µg PM 2.5 /m 3 ) or filtered air (FA, 2±1 µg PM 2.5 /m 3 ) in whole-body exposure chambers for up to 16 weeks. After 12 weeks, lung inflammatory cellrecruitment was evidenced by histology in UA-exposed mice. Interestingly, impaired redoxmetabolism, characterized by increased lung GSSG content, decreased SOD activity, andincreased NOX activation, preceded local inflammation in UA-exposed mice. Moreover, PM 2.5uptake and enhanced nitric oxide production was observed in alveolar macrophages fromUA-exposed mice by electron microscopy and flow cytometry, respectively, together withincreased proinflammatory cytokine levels (TNF-α and IL-6) in bronchoalveolar lavage andplasma. In the heart of UA-exposed mice, impaired tissue oxygen metabolism and alteredmitochondrial ultrastructure and function were observed, by decreased active staterespiration by 48%, inner membrane depolarization, decreased ATP production by 17%, andenhanced H 2 O 2 release by 39%. This scenario led to a significant increase in infarct sizefollowing in vivo myocardial ischemia/reperfusion injury, from 43±3% of the area at risk inFA-exposed mice to 66±4% in UA-exposed mice (p<0.01). Taken together, our data unravelsome of the pathways that might explain the adverse health effects of air pollution exposure,and ultimately highlights the importance of considering environmental factors in thedevelopment of cardiovascular diseases.