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Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System
Published on: October 22, 2020
Extracellular vesicle-encapsulated microRNA signatures of cigarette smoking and smoking-related harm
Christina M Eckhardt1, Wending Li2, Tessa R Bloomquist2
1Columbia University Vagelos College of Physicians and Surgeons, Department of Medicine, New York, NY, USA; Columbia University Mailman School of Public Health, Department of Environmental Health Sciences, New York, NY, USA.
Background:
The health effects of smoking vary substantially between individuals. Novel strategies are needed to identify individuals with increased risk of smoking-related morbidity. Extracellular vesicle-encapsulated microRNAs (EV-miRNAs) may be viable biomarkers of smoking-related harm. Here, we measured associations of smoking status with plasma EV-miRNA expression levels.
Methods:
Participants who were free of smoking-related diseases were sampled from the prospective Normative Aging Study (NAS). Smoking histories were evaluated using standardized smoking questionnaires. EV-miRNAs were measured in plasma. Vital status was monitored using death records. Associations of smoking status with EV-miRNA expression levels were modeled using linear regression. Results were validated in the Strong Heart Study (SHS). Associations of candidate EV-miRNAs with all-cause mortality were modeled using Cox proportional hazards models.
Results:
Among 88 NAS participants (mean age 70.9 ± 8.0 years), recent smoking was associated with differential expression of 16 plasma EV-miRNAs, including decreased expression of miR-30b-5p (fold change in EV-miRNA expression: 0.26, 95 % CI 0.11-0.58). The association between smoking and low miR-30b-5p expression was replicated in the SHS cohort (fold change: 0.71, 95 % CI 0.51-0.97). A pathway analysis showed miR-30b-5p targeted genes that modulate oncogenic and pro-inflammatory signaling pathways (q-value<0.05). In the NAS cohort, low miR-30b-5p expression was associated with higher all-cause mortality (adjusted Hazard Ratio 3.36, 95 % CI 1.35-8.35).
Conclusions:
Recent cigarette smoking was associated with low miR-30b-5p expression in two distinct populations. Circulating miR-30b-5p is a robust biomarker of smoking-related harm and may represent a novel target for the prevention and treatment of smoking-related diseases.

