Early Proteome Shift and Serum Bioactivity Precede Diesel Exhaust-induced Impairment of Cardiovascular Recovery in Spontaneously Hypertensive Rats

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/m 3 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.

Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function

“…D, Serum from GD20 O3-exposed rats (collected at GD21) impaired vasorelaxation in uterine arteries excised from unexposed dams. vascular endothelial cells, both in terms of vasodilation and barrier integrity (Aragon et al, 2017;Christophersen et al, 2016;Liberda et al, 2014;Mostovenko et al, 2019;Robertson et al, 2013;Thompson et al, 2019). Pulmonary nanotube exposure revealed the potential complexity of serum molecular modifications, with hundreds of biologically active modified/fragmented peptide sequences arising as cleavage products from endogenous proteins (Mostovenko et al, 2019).…”

Impact of Wildfires on Cardiovascular Health

“…As an alternative to laboratory-scale WFS inhalation, oropharyngeal aspiration of solubilized PM fractions in saline solution enables segregation of the cardiovascular outcomes mediated by particulates alone (Figure 3). 17,115,127 Following this approach, Thompson et al 128 delivered either a 35-µg (low) or a 350-µg (high) dose of PM from peat smoke to male Sprague-Dawley rats. The decline of both the ejection fraction and the fractional shortening of the LV, coupled with larger LV end diastolic volume in treated animals, suggested a role for PM in modulating the regulation of ejection and filling volumes via irritant or autonomic mechanisms (Figure 1).…”