EXPOSURE TO AIR POLLUTION FINE PARTICULATE MATTER (PM2.5) ALTERS EXPRESSION OF SYSTEMIC AND TISSUE-SPECIFIC COMPONENTS OF THE RENIN-ANGIOTENSIN SYSTEM

NARVÁEZ PARDO J; FREIRE A; DE LA FUENTE S; BARRALES B; MUÑOZ M; GIRONACCI M; BUCHHOLZ B; MAGNANI N; EVELSON P; DOMINICI F

Mar del Plata

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2023

Previous studies have implicated air pollution fine particulate matter(PM2.5) in various cardiovascular and cardiometabolic diseasestates. However, the molecular mechanisms by which these pollutantsmediate these comorbidities have not been fully elucidated.Dysregulation of the renin-angiotensin system (RAS) may be onepotential mechanism. To study the impact of PM2.5 on systemicand tissue components of the RAS, male 8-week-old Balb/C micewere exposed to filtered air (FA) or urban air (UA) from Buenos AiresCity, in whole-body exposure chambers for 14 weeks. Levelsof main RAS components including angiotensin converting enzyme(ACE) and ACE2, as well as AT1, AT2 and Mas receptors (R) abundancewere determined in kidney, heart and lung tissue by WesternBlotting (WB) and their corresponding mRNA expression wasdetected by RT-qPCR. Circulating angiotensin (Ang) II levels weredetermined by radioimmunoassay. Exposure to air pollution resultedin increased mRNA levels of ACE and MasR, and increased proteinlevels of ACE in the kidney; upregulated mRNA and protein abundanceof cardiac and pulmonary AT2R and MasR, together with increasedlevels of proteins nitrated at Tyr residues in both kidney andlung homogenates, indicative of nitrosative stress in these tissues.In addition, exposure to PM2.5 was associated with increased levelsof circulating Ang II, indicative of an exacerbation of the RAS. Ourfindings indicate that chronic exposure to air pollution induces analtered expression of both tissue and systemic components of theRAS. Given that both the AT2R and the MasR have been ascribedto participate in tissue-repair mechanisms, the upregulation of thesereceptors detected in mice heart and lung after chronic exposureto polluted air could represent a mechanism of tissue protectionagainst damage induced by PM2.5