Abstract

Single circulating factors are often investigated to explain air pollution-induced cardiovascular dysfunction, yet broader examinations of the identity and bioactivity of the entire circulating milieu remain understudied. The purpose of this study was to determine if exposure-induced cardiovascular dysfunction can be coupled with alterations in both serum bioactivity and the circulating proteome. Two cohorts of Spontaneously Hypertensive Rats (SHRs) were exposed to 150 or 500 μg/m3 diesel exhaust (DE) or filtered air (FA). In Cohort 1, we collected serum 1 hour after exposure for proteomics analysis and bioactivity measurements in rat aortic endothelial cells (RAECs). In Cohort 2, we assessed left ventricular pressure (LVP) during stimulation and recovery from the sympathomimetic dobutamine HCl, one day after exposure. Serum from DE-exposed rats had significant changes in 66 serum proteins and caused decreased NOS activity and increased VCAM-1 expression in RAECs. While rats exposed to DE demonstrated increased heart rate at the start of LVP assessments, heart rate, systolic pressure, and double product fell below baseline in DE-exposed rats compared to FA during recovery from dobutamine, indicating dysregulation of post-exertional cardiovascular function. Taken together, a complex and bioactive circulating milieu may underlie air pollution-induced cardiovascular dysfunction.

Details

Title
Early Proteome Shift and Serum Bioactivity Precede Diesel Exhaust-induced Impairment of Cardiovascular Recovery in Spontaneously Hypertensive Rats
Author
Thompson, Leslie C 1   VIAFID ORCID Logo  ; Shannahan, Jonathan H 2 ; Perez, Christina M 3 ; Haykal-Coates Najwa 1 ; King, Charly 1 ; Hazari, Mehdi S 1 ; Brown, Jared M 4 ; Farraj, Aimen K 1 

 U.S. Environmental Protection Agency, Environmental Public Health Division, Research Triangle Park, USA (GRID:grid.418698.a) (ISNI:0000 0001 2146 2763) 
 School of Health Sciences, Purdue University, West Lafayette, USA (GRID:grid.169077.e) (ISNI:0000 0004 1937 2197) 
 College of the Mainland, Texas City, USA (GRID:grid.421331.6) (ISNI:0000 0001 0355 383X) 
 University of Colorado Anschutz Medical Campus, Department of Pharmaceutical Sciences, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2219593206
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.