Exposure to WTC Dust Alters Rat Cardiac Gap Junctional Proteins

Abstract

ObjectiveFirst responders (FR) present at Ground Zero during the first 72 h after the World Trade Center (WTC) towers collapsed have exhibited increased incidences of cardiovascular disease (CVD) risk. Despite increasing evidences of CVDs, the mechanistic underpinnings behind adverse effects of WTC dust exposure are not well studied. Using a system that generated/delivered supercoarse (10–53 μm) WTC dusts (in a manner that mimicked FR exposures), this study sought to examine potential toxicities in the heart.MethodsIn this study, rats were exposed on two consecutive days for 2 h/day by intratracheal inhalation (ITIH) to supercoarse (10–53 μm) WTC dusts (while under isoflurane [ISO] anesthesia) or an air/ISO (naïve) mixture. This dose conservatively modeled likely exposures to nearly ≈250 mg dust/m3 FR exposure. Hearts were harvested 30 & 60 days post‐exposure and processed for qualitative and quantitative protein expression analyses.ResultsData obtained from right ventricular samples demonstrate decreased desmin expression in the WTC exposed group as compared to the control groups (naive and ISO). Interestingly, although no change in the expression of connexin‐43 was observed between the exposed and control groups, localization studies using confocal microscopy revealed disrupted organization of connexin‐43 at the cardiomyocyte junction. Additionally, confocal imaging suggested reduction of F‐actin expression in the WTC exposed group compared to control groups. Further, expression profiles of the PI3K/Akt signaling axis using western blot analysis revealed a marked decrease in activated phospho‐Akt in the WTC dust exposed group in comparison to control groups. Although blunted activation of Akt was observed, phospho‐PI3K levels were unaltered.ConclusionExposure to WTC dusts caused significant remodeling of gap junctions and altered expression of selected mechanical junction proteins at the intercalated disks. These results illustrate that a defect in a structural/gap junction protein can cause alterations in structural integrity leading to electrical and mechanical perturbations that can contribute to cardiac dysfunction.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.