Exposure to Fine Particulate Matter Air Pollution Alters mRNA and miRNA Expression in Bone Marrow-Derived Endothelial Progenitor Cells from Mice

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.

Air pollution exposure may impact the composition of human milk oligosaccharides

“…Additionally, during pregnancy there are DNA methylation changes that occur in mammary epithelial cells 49 where studies suggest that epigenetics may play an role in mammary gland development and function 50 . Additionally, exposure to air www.nature.com/scientificreports/ pollution has been linked with circulating miRNAs 51,52 , which may alter gene expression and HMO composition via impacts on the mammary gland 53,54 . Given that there is a genetic component of HMO biosynthesis 55 , and HMOs are solely made in the mammary gland, evaluating the effect of air pollution on HMO composition warrants further research.…”

Air Pollution Exposure Induces Vascular Injury and Hampers Endothelial Repair by Altering Progenitor and Stem Cells Functionality

“…However, it appears that different EPC subpopulations are differentially affected by PM exposure. Diverse effects based on particles size have been reported in various studies ( Table 2 ), all indicating that EPCs are early, sensitive, and direct targets of air pollution exposure ( Liberda et al, 2010 ; O'Toole et al, 2010 ; Haberzettl et al, 2012 ; Niu et al, 2013 ; Brook et al, 2013 ; Liberda et al, 2014 ; DeJarnett et al, 2015 ; Jantzen et al, 2016 ; Haberzettl et al, 2018 ; Li et al, 2021 ).…”

“…Likewise, the upregulation of the pro-inflammatory cytokine Ccl5 suggests a mechanism by which PM 2.5 -exposed EPCs remain in an early, immature state, and thus inefficient in promoting vascular repair. All these results suggest that PM 2.5 -induced changes in gene expression may contribute to EPC dysfunction and such changes may contribute to the adverse cardiovascular outcomes of air pollution exposure ( Li et al, 2021 ).…”