Short-term exposures to air pollutants affect mitochondrial DNA copy number in patients with acute coronary syndromes

Abstract Background Epidemiological studies have shown that exposure to air pollutants significantly increases the morbidity and mortality associated with coronary artery disease (CAD). However, despite well-documented epidemiological links, the molecular pathways remain poorly understood. As central regulators of cellular energy metabolism and reactive oxygen species production, mitochondria are highly susceptible to environmental stressors. Consequently, mitochondrial dysfunction may be a key contributor to the adverse cardiovascular effects of air pollution. Purpose This study aimed to investigate whether exposure to particulate matter may influence mitochondrial function in patients with angiographically documented CAD. Methods We recruited 144 patients with acute coronary syndrome (ACS, n=82; 84% male; 62±9 years) or stable angina (SA, n=62; 77% male 65±10 years) who were submitted to coronary angiography. All patients were residents of Milan, where daily air pollutant concentrations (PM2.5 and PM10) and meteorological data (temperature and humidity) were collected from fixed monitoring stations. Air pollutant concentration was averaged as short- (1 month) and long-term (1 year) before the time of coronary angiography for the case period. Mitochondrial DNA copy number (mtDNAcn), a marker of mitochondrial health reflecting the balance between mitochondrial biogenesis and degradation, was measured by real-time PCR. Blood biomarkers of systemic inflammation were determined including neutrophil-lymphocyte ratio (NLR) and systemic inflammatory response index (SII). Results Short- and long-term exposure did not show significantly difference in patients with ACS compared to SA. However, the adjusted multiple linear regression model, stratified by SA and ACS groups, revealed that short-term exposure to PM2.5, and PM10 was inversely associated with mtDNAcn in the ACS only, but not in the SA group. Conversely, no association was observed between long-term particulate matter exposure and mtDNAcn in either group (Figure). Spearman correlation analysis performed in the overall population showed a significant correlation between short- and long-term exposure of PM10 (Rho=0.168 p=0.045 and Rho=0.210 p=0.012, respectively) with NLR and PM10 (Rho=0.248 p=0.003 and Rho=0.210 p=0.012, respectively) and PM2.5 (Rho=0.221 p=0.008 and Rho=0.188 p=0.025, respectively) with SII. Moreover, mtDNAcn negatively correlated with NLR (Rho=-0.285, p=0.001) and with SII (Rho=-0.169, p=0.044). Conclusions Short-term exposure to PM2.5 and PM10 is associated with low levels of mtDNAcn in ACS group and mtDNAcn is negatively correlated with NLR and SII in all patients. These findings suggest that oxidative stress and inflammation may induce mitochondrial dysfunction, as reflected by decreased mtDNAcn, potentially mediating the adverse health effects of air pollution on plaque vulnerability and acute events.Figure