Citation:

Thompson, L., J. Shanahan, C. Perez, N. Coates, C. King, M. Hazari, J. Brown, AND A. Farraj. Early Proteome Shift and Serum Bioactivity Precede Diesel Exhaust-induced Impairment of Cardiovascular Recovery in Spontaneously Hypertensive Rats. Scientific Reports. Nature Publishing Group, London, Uk, 9(1):6885, (2019). https://doi.org/10.1038/s41598-019-43339-8

Impact/Purpose:

Evidence from epidemiological and clinical exposure studies links systemic inflammation with adverse cardiovascular outcomes after air pollution exposure. This study enhances the plausibility of the hypothesis that circulating factors may precipitate cardiac dysfunction by coupling demonstrations of enhanced endothelial bioactivity of serum collected from diesel exhaust-exposed animals with measurable changes in cardiac function. Moreover, a potential mechanistic role for systemic inflammatory responses in air pollution-induced cardiovascular dysfunction is further supported by the identification of credible candidate proteins and pathways, i.e. the acute phase response, with well-established linkages to cardiovascular disease. Thus, the identification of plausible biological mechanisms may increase confidence in epidemiological findings and in turn help reduce the uncertainty in standard setting.

Description:

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.

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