Abstract
Exposure to fine particulate matter (PM2.5) air pollution is associated with quantitative deficits of circulating endothelial progenitor cells (EPCs) in humans. Related exposures of mice to concentrated ambient PM2.5 (CAP) likewise reduces levels of circulating EPCs and induces defects in their proliferation and angiogenic potential as well. These changes in EPC number or function are predictive of larger cardiovascular dysfunction. To identify global, PM2.5-dependent mRNA and miRNA expression changes that may contribute to these defects, we performed a transcriptomic analysis of cells isolated from exposed mice. Compared with control samples, we identified 122 upregulated genes and 44 downregulated genes in EPCs derived from CAP-exposed animals. Functions most impacted by these gene expression changes included regulation of cell movement, cell and tissue development, and cellular assembly and organization. With respect to miRNA changes, we found that 55 were upregulated while 53 were downregulated in EPCs from CAP-exposed mice. The top functions impacted by these miRNA changes included cell movement, cell death and survival, cellular development, and cell growth and proliferation. A subset of these mRNA and miRNA changes were confirmed by qRT-PCR, including some reciprocal relationships. These results suggest that PM2.5-induced changes in gene expression may contribute to EPC dysfunction and that such changes may contribute to the adverse cardiovascular outcomes of air pollution exposure.
Highlights
IntroductionAnalysis of abundant epidemiological data has identified robust associations between exposure to fine particulate matter (PM2.5 ) air pollution and adverse health outcomes in general [1], and cardiovascular disease in particular [2,3]
Our results identified differentially expressed mRNAs and miRNAs and those cellular functions impacted by these changes, further clarifying the mechanistic basis of PM2.5 -induced cardiovascular disease
Compared with control cells isolated from mice breathing filtered air, we identified multiple mRNAs and miRNAs that were either upregulated or downregulated in exposed mice
Summary
Analysis of abundant epidemiological data has identified robust associations between exposure to fine particulate matter (PM2.5 ) air pollution and adverse health outcomes in general [1], and cardiovascular disease in particular [2,3] These studies have linked acute exposure to PM2.5 with an increased incidence of myocardial infarction, stroke, cardiac arrhythmias, and sudden cardiac death [3,4,5], while chronic exposures appear to accelerate the progression of atherosclerotic disease [6,7]. Does the endothelial layer provide a physical separation between blood and surrounding tissue, it plays an essential role in immune responses, thrombosis, and the control of blood pressure. The maintenance of vascular homeostasis is essential for overall health
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