Longitudinal Impact of WTC Dust Inhalation on Rat Cardiac Tissue Transcriptomic Profiles.

Sung-Hyun Park,Thomas Kluz,Maureen Sisco,Loren E Wold,Yuting Lu,Lori Horton,Matthew W Gorr,Hong Sun,Colette Prophete,Mitchell D Cohen,Judith Zelikoff,Lung-Chi Chen,Max Costa,Yongzhao Shao,Hyun-Wook Lee

doi:10.3390/ijerph19020919

Abstract

First responders (FR) exposed to the World Trade Center (WTC) Ground Zero air over the first week after the 9/11 disaster have an increased heart disease incidence compared to unexposed FR and the general population. To test if WTC dusts were causative agents, rats were exposed to WTC dusts (under isoflurane [ISO] anesthesia) 2 h/day on 2 consecutive days; controls received air/ISO or air only. Hearts were collected 1, 30, 240, and 360 d post-exposure, left ventricle total RNA was extracted, and transcription profiles were obtained. The data showed that differentially expressed genes (DEG) for WTC vs. ISO rats did not reach any significance with a false discovery rate (FDR) < 0.05 at days 1, 30, and 240, indicating that the dusts did not impart effects beyond any from ISO. However, at day 360, 14 DEG with a low FDR were identified, reflecting potential long-term effects from WTC dust alone, and the majority of these DEG have been implicated as having an impact on heart functions. Furthermore, the functional gene set enrichment analysis (GSEA) data at day 360 showed that WTC dust could potentially impact the myocardial energy metabolism via PPAR signaling and heart valve development. This is the first study showing that WTC dust could significantly affect some genes that are associated with the heart/CV system, in the long term. Even > 20 years after the 9/11 disaster, this has potentially important implications for those FR exposed repeatedly at Ground Zero over the first week after the buildings collapsed.

Highlights

The results of this study showed that repeated exposures to Ground Zero World Trade Center (WTC) dust were able to impact changes in gene expression in the hearts of exposed rats
The WTC dust was found to affect gene expression that could influence a variety of heart/cardiovascular functions, including coronary artery disease, heart development, cardiac fibrosis, myocardial hypertrophy, myocardial infarct, heart failure, etc
A new exposure method is being developed that will not require isoflurane anesthesia (ISO), it will allow for equivalent WTC dust delivery into the lungs, and will reiterate many of the outcomes seen here

Summary

Introduction

In the years since the 9/11 disaster, chronic health problems continue to become evident among firefighters/rescue personnel (First responders; FR) who were at the World. Trade Center (WTC) Ground Zero for repeated/prolonged periods during the first 72 h post-collapse [1,2]. Evidence from clinical studies and data accumulated by the WTC. Even so, underlying reasons for the development of these disorders in the FR remain undefined. To date, one major problem that has remained unresolved in these subsequent 20 years has been that underlying reasons for development of these disorders in the FR remain undefined. It has still not been established if

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