Blog
About

1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references 52

          • Record: found
          • Abstract: found
          • Article: not found

          Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells.

          Decreased nitric oxide (NO) activity, the formation of reactive oxygen species, and increased endothelial expression of the redox-sensitive vascular cell adhesion molecule 1 (VCAM-1) gene in the vessel wall are early and characteristic features of atherosclerosis. To explore whether these phenomena are functionally interrelated, we tested the hypothesis that redox-sensitive VCAM-1 gene expression is regulated by a NO-sensitive mechanism. In early passaged human umbilical vein endothelial cells and human dermal microvascular endothelial cells, the NO donor diethylamine-NO (DETA-NO, 100 microM) reduced VCAM-1 gene expression induced by the cytokine tumor necrosis factor alpha (TNF-alpha, 100 units/ml) at the cell surface level by 65% and intracellular adhesion molecule 1 (ICAM-1) gene expression by 35%. E-selectin gene expression was not affected. No effect on expression of cell adhesion molecules was observed with DETA alone. Moreover, DETA-NO suppressed TNF-alpha-induced mRNA accumulation of VCAM-1 and TNF-alpha-mediated transcriptional activation of the human VCAM-1 promoter. Conversely, treatment with NG-monomethyl-L-arginine (L-NMMA, 1 mM), an inhibitor of NO synthesis, augmented cytokine induction of VCAM-1 and ICAM-1 mRNA accumulation. By gel mobility shift analysis, DETA-NO inhibited TNF-alpha activation of DNA binding protein activity to the VCAM-1 NF-kappa B like binding sites. Peroxy-fatty acids such as 13-hydroperoxydodecanoeic acid (linoleyl hydroperoxide) may serve as an intracellular signal for NF-kappa B activation. Using thin layer chromatography, DETA-NO (100 microM) suppressed formation of this metabolite, suggesting that DETA-NO modifies the reactivity of oxygen intermediates in the vascular endothelium. Through this mechanism, NO may function as an immunomodulator of the vessel wall and thus mediate inflammatory events involved in the pathogenesis of atherosclerosis.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            CD40, an extracellular receptor for binding and uptake of Hsp70–peptide complexes

            Tumor and viral antigens elicit a potent immune response by heat shock protein–dependent uptake of antigenic peptide with subsequent presentation by MHC I. Receptors on antigen-presenting cells that specifically bind and internalize a heat shock protein–peptide complex have not yet been identified. Here, we show that cells expressing CD40, a cell surface protein crucial for B cell function and autoimmunity, specifically bind and internalize human Hsp70 with bound peptide. Binding of Hsp70–peptide complex to the exoplasmic domain of CD40 is mediated by the NH2-terminal nucleotide–binding domain of Hsp70 in its ADP state. The Hsp70 cochaperone Hip, but not the bacterial Hsp70 homologue DnaK, competes formation of the Hsp70–CD40 complex. Binding of Hsp70-ADP to CD40 is strongly increased in the presence of Hsp70 peptide substrate, and induces signaling via p38. We suggest that CD40 is a cochaperone-like receptor mediating the uptake of exogenous Hsp70–peptide complexes by macrophages and dendritic cells.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              In-cabin commuter exposure to ultrafine particles on Los Angeles freeways.

              Worldwide people are exposed to toxic ultrafine particles (UFP, with diameters (dp) less than 100 nm) and nanoparticles (NP, dp < 50 nm) under a variety of circumstances. To date, very limited information is available on human exposure to freshly emitted UFP and NP while traveling on major roads and freeways. We report in-cabin and outdoor measurements of particle number concentration and size distributions while driving three vehicles on Los Angeles freeways. Particle number concentrations and size distributions were measured under different vehicle ventilation settings. When the circulation fan was set to on, with substantial external air intake, outside changes in particle counts caused corresponding in-cabin changes approximately 30-60 s later, indicating an maximal air exchange rate of about 120-60 h(-1). Maximum in-cabin protection (approximately 85%) was obtained when both fan and recirculation were on. In-cabin and outdoor particle size distributions in the 7.9-217 nm range were observed to be mostly bimodal, with the primary peak occurring at 10-30 nm and the secondary at 50-70 nm. The vehicle's manufacture-installed particle filter offered an in-cabin protection of about 50% for particles in the 7-40 nm size range and 20-30% for particles in the 40 to approximately 200 nm size range. For an hour daily commute exposure, the in-vehicle microenvironment contributes approximately 10-50% of people's daily exposure to UFP from traffic.
                Bookmark

                Author and article information

                Contributors
                jared.brown@ucdenver.edu
                Farraj.aimen@epa.gov
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                3 May 2019
                3 May 2019
                2019
                : 9
                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
                Article
                43339
                10.1038/s41598-019-43339-8
                6499793
                31053794
                © The Author(s) 2019

                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/.

                Funding
                Funded by: FundRef https://doi.org/10.13039/100000002, U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH);
                Award ID: K99 ES024392
                Award ID: R01 ES019311
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized

                biomarkers, cardiovascular biology

                Comments

                Comment on this article