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.
Highlights
An emerging alternative applied in recent studies is the assessment of the bioactivity of serum or plasma collected from subjects after exposure
This study provides evidence indicating that diesel exhaust (DE) exposure impacts serum bioactivity, the circulating proteome, and cardiovascular function in Spontaneously Hypertensive Rats (SHRs)
Relative to SHRs exposed to filtered air, a single 4-hour diesel exhaust (DE) inhalation exposure resulted in impairment of postexertional cardiovascular function one day later during recovery from pharmacological challenge with the sympathomimetic dobutamine
Summary
An emerging alternative applied in recent studies is the assessment of the bioactivity of serum or plasma collected from subjects after exposure This bioactivity describes the potential for a suite of serum or plasma-bound factors to collectively alter cellular, tissue, and systemic organ function. Serum collected from mice after exposure to mixed combustion emissions or wood smoke altered vascular reactivity of aortic rings collected from unexposed mice[12] These approaches are predicated on the assumption that in vivo responses will in part mirror those measured ex vivo. We integrate the findings to speculate on potential systemic mechanisms that drove the in vivo responses and suggest future studies to further elucidate mechanisms of action
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