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

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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.

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Urban particulate matter triggers lung inflammation via the ROS-MAPK-NF-κB signaling pathway.

Jian Wang, Jianan Huang, Linlin Wang … (2017)

Particulate matter (PM) is a high risk factor for various respiratory diseases and triggers an inflammatory response in lung tissues. However, the molecular mechanism of the PM-induced inflammatory response is incompletely understood.

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PM 2.5 -induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-κB-dependent pathway

Chen-Wei Liu, Tzu-Lin Lee, Yu-Chen Chen … (2018)

Background Epidemiological studies have shown that ambient air pollution is closely associated with increased respiratory inflammation and decreased lung function. Particulate matters (PMs) are major components of air pollution that damages lung cells. However, the mechanisms remain to be elucidated. This study examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1) expression and the related mechanisms in vitro and in vivo. Result The cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to A549 cells were more severely affected by treatment with O-PMs (organic solvent-extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of SRM1649b). We observed a significant increase in ICAM-1 expression by O-PMs, but not W-PMs. O-PMs also induced the phosphorylation of AKT, p65, and STAT3. Pretreating A549 cells with N-acetyl cysteine (NAC), an antioxidant, attenuated O-PMs-induced ROS generation, the phosphorylation of the mentioned kinases, and the expression of ICAM-1. Furthermore, an AKT inhibitor (LY294002), NF-κB inhibitor (BAY11–7082), and STAT3 inhibitor (Stattic) significantly down-regulated O-PMs-induced ICAM-1 expression as well as the adhesion of U937 cells to epithelial cells. Interleukin-6 (IL-6) was the most significantly changed cytokine in O-PMs-treated A549 cells according to the analysis of the cytokine antibody array. The IL-6 receptor inhibitor tocilizumab (TCZ) and small interfering RNA for IL-6 significantly reduced ICAM-1 secretion and expression as well as the reduction of the AKT, p65, and STAT3 phosphorylation in O-PMs-treated A549 cells. In addition, the intratracheal instillation of PMs significantly increased the levels of the ICAM-1 and IL-6 in lung tissues and plasma in WT mice, but not in IL-6 knockout mice. Pre-administration of NAC attenuated those PMs-induced adverse effects in WT mice. Furthermore, patients with chronic obstructive pulmonary disease (COPD) had higher plasma levels of ICAM-1 and IL-6 compared to healthy subjects. Conclusion These results suggest that PMs increase ICAM-1 expression in pulmonary epithelial cells in vitro and in vivo through the IL-6/AKT/STAT3/NF-κB signaling pathway. Electronic supplementary material The online version of this article (10.1186/s12989-018-0240-x) contains supplementary material, which is available to authorized users.

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The crosstalk between autonomic nervous system and blood vessels.

Yulan Sheng, Li Li Zhu (2018)

The autonomic nervous system (ANS), comprised of two primary branches, sympathetic and parasympathetic nervous system, plays an essential role in the regulation of vascular wall contractility and tension. The sympathetic and parasympathetic nerves work together to balance the functions of autonomic effector organs. The neurotransmitters released from the varicosities in the ANS can regulate the vascular tone. Norepinephrine (NE), adenosine triphosphate (ATP) and Neuropeptide Y (NPY) function as vasoconstrictors, whereas acetylcholine (Ach) and calcitonin gene-related peptide (CGRP) can mediate vasodilation. On the other hand, vascular factors, such as endothelium-derived relaxing factor nitric oxide (NO), and constriction factor endothelin, play an important role in the autonomic nervous system in physiologic conditions. Endothelial dysfunction and inflammation are associated with the sympathetic nerve activity in the pathological conditions, such as hypertension, heart failure, and diabetes mellitus. The dysfunction of the autonomic nervous system could be a risk factor for vascular diseases and the overactive sympathetic nerve is detrimental to the blood vessel. In this review, we summarize findings concerning the crosstalk between ANS and blood vessels in both physiological and pathological conditions and hope to provide insight into the development of therapeutic interventions of vascular diseases.

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Author and article information

Contributors

Jared M. Brown: jared.brown@ucdenver.edu

Aimen K. Farraj: Farraj.aimen@epa.gov

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 3 May 2019

Publication date PMC-release: 3 May 2019

Publication date Collection: 2019

Volume: 9

Electronic Location Identifier: 6885

Affiliations

[1 ]ISNI 0000 0001 2146 2763, GRID grid.418698.a, Environmental Public Health Division, , U.S. Environmental Protection Agency, ; Research Triangle Park, NC USA

[2 ]ISNI 0000 0004 1937 2197, GRID grid.169077.e, School of Health Sciences, Purdue University, ; West Lafayette, IN USA

[3 ]ISNI 0000 0001 0355 383X, GRID grid.421331.6, College of the Mainland, ; Texas City, TX USA

[4 ]ISNI 0000 0001 0703 675X, GRID grid.430503.1, Department of Pharmaceutical Sciences, , University of Colorado Anschutz Medical Campus, ; Aurora, CO USA

Author information

Leslie C. Thompson http://orcid.org/0000-0003-2322-3744

Article

Publisher ID: 43339

DOI: 10.1038/s41598-019-43339-8

PMC ID: 6499793

PubMed ID: 31053794

SO-VID: 4a9cbf96-7a3c-4ab0-a1f1-a751609913e5

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 28 November 2018

Date accepted : 18 April 2019

Funding

Funded by: FundRef https://doi.org/10.13039/100000002, U.S. Department of Health & Human Services | National Institutes of Health (NIH);

Award ID: K99 ES024392

Award ID: R01 ES019311

Award Recipient : Jonathan H. Shannahan Jared M. Brown

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ScienceOpen disciplines: Uncategorized

Keywords: cardiovascular biology,biomarkers

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ScienceOpen disciplines: Uncategorized

Keywords: cardiovascular biology, biomarkers

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

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Journal of Circulating Biomarkers

Most cited references 52

Urban particulate matter triggers lung inflammation via the ROS-MAPK-NF-κB signaling pathway.

PM 2.5 -induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-κB-dependent pathway

The crosstalk between autonomic nervous system and blood vessels.

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