Short-term exposures to air pollutants affect mitochondrial DNA copy number in patients with acute but not in chronic coronary syndromes

Epidemiological studies link pollution to higher coronary artery disease (CAD) risk, but the molecular pathways remain unclear. Mitochondria may play a role due to their sensitivity to pollutants. This study assesses the impact of air pollution on mitochondrial DNA copy number (mtDNAcn) in patients with angiographically documented CAD. We performed a prospective single-center cohort design by enrolling 151 patients undergoing coronary angiography in the Milan area: 89 with acute coronary syndrome (ACS), and 62 with chronic coronary syndrome (CCS). Daily levels of PM2.5, PM10, and meteorological data were collected from fixed monitoring stations. Exposure was averaged over short- (1 week, 2 weeks, 3 weeks and 1 month) and long-term (1 year) periods before angiography. mtDNAcn, was measured by real-time PCR. Systemic inflammatory index (SII) was calculated from the complete blood count. ACS patients were exposed to significantly higher short-term levels of PM2.5 and PM10 and a greater number of days exceeding their recommended annual limits, compared to the CCS group. Multivariable linear regression showed that short-term exposure to PM2.5 and PM10 was inversely associated with mtDNAcn in ACS. Specifically, an interquartile range increase of 21.02 µg/m3 in 3-week PM2.5, 19.13 µg/m3 in 1-month PM2.5, and 23.03 µg/m3 in 1-month PM10 was associated with decreases in mtDNAcn of 28.00%, 29.51%, and 17.36%, respectively. mtDNAcn also negatively correlated with SII (P = 0.028) in the study population. Short-term exposure to PM2.5 and PM10 is associated to reduce mtDNAcn in ACS., supporting a potential role of mitochondrial dysfunction in the pathogenesis of acute events and plaque vulnerability.