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

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

Congreso; Free Radical Biology and Medicine; 2021

The World Health Organization estimates that 91% of the world´s populationbreathe low quality air. As a consequence, 7 million premature deaths occurevery year due to air pollution exposure. From those, myocardial infarction (MI) accounts for 2.4 million deaths yearly, which represents 25% of the totalglobal burden for this disease. Here, we aimed to understand some of themechanisms by which urban air pollution exposure aggravates MI, focusing onthe effects of airborne fine particulate matter (PM2.5) on lung redox metabolism and cardiac mitochondrial structure and function. Male 8-week-oldBALB/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 histologyin UA-exposed mice. Interestingly, impaired redox metabolism, characterizedby increased lung GSSG content, decreased SOD activity, and increased NOXactivation, preceded local inflammation in UA-exposed mice. Moreover, PM2.5uptake 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-αand IL-6) in bronchoalveolar lavage and plasma. In the heart of UA-exposedmice, 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%, andenhanced H2O2 release by 39%. This scenario led to a significant increase ininfarct size following in vivo myocardial ischemia/reperfusion injury, from433% of the area at risk in FA-exposed mice to 664% in UA-exposed mice(p