Abstract
Acute and chronic exposures to particulate matter (PM2.5) air pollution increase the risk for cardiovascular disease (CVD). A hypothesized mechanism linking PM2.5 exposure and CVD is the induction of endothelial dysfunction - a key step to increased CVD risk. Although PM2.5 exposure is associated with endothelial dysfunction and the vasoconstrictor peptide endothelin-1 (ET-1) is upregulated in endothelial dysfunction, the effects of PM2.5 on ET-1 and whether or not ET-1 mediates the downstream effects of PM2.5 are unclear. In addition to examining associations between acute changes in ambient PM2.5 and circulating levels of ET-1, we also looked at whether changes in ET-1 were associated with changes in markers of vascular health and systemic injury. For example, endothelial function is maintained in part by circulating angiogenic cell (CAC)-mediated repair, and our recent studies show that CACs in humans and mice are decreased by ambient PM2.5 exposure. In the current study, we recruited young, healthy adults who were exposed to natural variations in PM2.5, and we analyzed associations between PM2.5 and circulating levels of ET-1, between ET-1 and CACs, and between ET-1 and other biomarkers of injury using linear regression analyses. Surprisingly, ET-1 levels were negatively associated with PM2.5 levels (β = −0.773, P = 0.0005), yet, in contrast, positively associated with two CACs: CAC-2 (CD31+/CD34+/CD45+) and CAC-4 (CD31+/CD34+/CD45+/CD133+). Interestingly, ET-1 levels were negatively associated with some biomarkers (platelet factor 4, β = −0.148, P = 0.0003; triglycerides, β = −0.095, P = 0.041) and positively with other biomarkers: albumin (β = 0.035, P = 0.006) and IL-lβ (β = 0.082, P = 0.012). These findings further reveal the insidious nature of PI2.5’s anti-angiogenic effect including a novel relationship between ET-1 and CACs in young adults exposed to acute elevations of air pollution.
Highlights
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and the risk of cardiovascular events is greatly increased by exposure to air pollution [1]
Plasma ET-1 has been associated with the development of endothelial dysfunction [4], and it has been reported that the production and function of ET-1 and its receptors are upregulated in a number of disease states associated with endothelial dysfunction, including hypertension and atherosclerosis [5,6,7,8]
Significant associations were seen between PM2.5 and non-albumin protein, platelet factor 4 (PF-4), stromal cell-derived factor-1 (SDF-1), and total plasma protein (Table 2; Supplemental Figure 1), consistent with our previous study [15]
Summary
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and the risk of cardiovascular events is greatly increased by exposure to air pollution [1]. There is a strong association between endothelial dysfunction and CVD [4], as exemplified by concurrent decreased formation and/or bioactivity of the vasodilator nitric oxide and increased levels and/or activity of the endothelial-derived vasoconstrictor endothelin-1 (ET-1) [4]. Changes in ET-1 have been associated with changes in both inflammatory [9,10] and thrombotic [11] factors, further increasing the potential for the development of endothelial injury and dysfunction. PM2.5 exposure suppresses CACs and growth factor levels and simultaneously increases inflammatory markers in young healthy adults that likely primes the endothelium for injury and development of CVD [14,15,16]
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