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Regulation of MicroRNA Expression in the Lungs by Exposure to Air Pollution & Antigen


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Conference: 2014 International PHA Conference and Scientific Sessions

Release Date: 06.22.2014

Presentation Type: Abstracts

File Download: 2014 Conference Abstract - Lucas B

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Background: Pulmonary Hypertension is characterized by pulmonary arterial remodeling and increased pressure in the pulmonary circulation. It is often associated with inflammation in the lungs and can lead to right heart failure. Our work shows that urban ambient pollution exacerbates the experimental antigen-induced pulmonary hypertension phenotype just like other types of inflammatory lung conditions. 

Methods: We aimed to identify microRNAs (miRNAs) that are differentially expressed in our mouse model using quantitative PCR analysis of lung tissue samples. In addition, we examined plasma samples for miRNA levels from individuals occupationally exposed to high levels of air pollution or cigarette smoke, and from controls.

Results: Our study is the first to show significantly de-regulated expression of three microRNA species (miR-135a, miR-21, miR-204) in the lungs of mice that were exposed to antigen and particulate matter and developed pulmonary hypertension. De-regulated levels of miR-21 and miR-204 have been reported in human pulmonary hypertension and in experimental pulmonary hypertension. MiR-135a is targeting several transcription factors important for immune and remodeling responses. Upregulated miR-135a expression has been reported in experimental asthma. Using human samples, our study showed that plasma levels of miR-21 and miR-135a, but not levels of miR-204, clustered individuals with high dose exposures and individuals with low dose environmental exposures. 

Conclusions:  In conclusion, our study has identified miRNAs that may indicate an at-risk state of the pulmonary vasculature. Current studies are aimed at identifying the cytokines that control the expression of these miRNAs. Further mechanistic studies knock-down or over-expression experiments will need to determine the role of these miRNAs in experimental pulmonary hypertension.

Funding Support: National Institutes of Health 1R21HL092370-01 (GG), 1R01 HL095764-01 (GG); American Heart Association, Founders affiliate (0855943D, GG); Stony Wold – Herbert Fund, New York (SHP); NIEHS center grant (ES00260); Cancer Center Support Grant (5P30CA016087-31)