Air Pollution and Tobacco Smoke Differentially Depress Circulating Angiogenic Cells in Humans

Background: There is considerable epidemiological evidence linking environmental exposures such as fine particulate matter (PM_2.5) and tobacco smoke with increased cardiovascular disease (CVD) risk. Although endothelial dysfunction is considered a shared effect of these toxins, it is unclear whether these exposures induce injury by a shared mechanism. Hence, we assessed whether levels of circulating angiogenic cells (CACs), a surrogate marker of endothelium health, were associated with PM_2.5 and tobacco smoke exposure.

 

Methods: CACs were identified by the presence of stem cell-related antigens (CD34 and AC133) using flow cytometry. In a cross-sectional analysis, we measured 15 antigenically-distinct CACs in 316 participants. Daily mean PM_2.5 data at the community level were acquired from EPA-validated monitors, and tobacco smoke exposure was assessed via self-report. Generalized linear models were used to assess the association between PM_2.5 and/or tobacco smoke exposure and CAC levels.

 

Results: Study participants were 50±10 years old, 40% African American, 49% female, and 35% smokers. Regression analyses were adjusted for potential confounders: age, gender, ethnicity, body mass index, diabetes, myocardial infarction, and socioeconomic status. In general, CAC (CD34⁺) levels were inversely associated with either PM_2.5 or tobacco smoke exposure such that PM_2.5 suppressed early/immature (AC133⁺) cells while current smokers had significantly fewer mature (AC133^-) CACs in peripheral blood.

Conclusions: Exposure to PM_2.5 appears to suppress an immature CAC phenotype, implying a mechanism targeting bone marrow development of CACs, whereas tobacco smoke appears to deplete more mature CACs, which are important for vascular injury repair. Although both exposures induce endothelial dysfunction and increase CVD risk, herein we demonstrate that these pollutants induce vascular injury via different mechanisms. These findings suggest that CACs are sensitive markers of environmental exposures, and thus, this relationship between vascular health, tobacco smoke exposure, and ambient PM_2.5 may further facilitate the development and promulgation of environmental pollutant standards.