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      The effect of subacute lead exposure on selected blood inflammatory biomarkers and angiogenetic factors

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          Abstract

          Objectives:

          The aim of the study was to examine blood levels of selected pro-inflammatory cytokines, C reactive protein (CRP), and selected factors that influence angiogenesis in workers exposed to lead for a short period of time.

          Methods:

          The study population consisted of 36 male workers (mean age 41 ± 14 years) exposed to lead for 40 days.

          Results:

          The mean blood lead level (BLL) was 10.7 ± 7.67 μg/d l at the beginning of the study, and increased to 49.1 ± 14.1 μg/d l at the end of the study period. The levels of macrophage inflammatory protein 1-α (MIP-1α) were significantly higher after the studied exposure to lead compared to the baseline by 71%. Similarly, the values of CRP increased by 35%. Conversely, the values of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and fibroblast growth factor-basic (FGF-basic) decreased by 14% and 21%, respectively. After the examined period of lead exposure, analysis of correlations showed positive correlations between vascular endothelial growth factor (VEGF) levels and the levels of interleukin 1β (IL-1β) (R = 0.39), interleukin 6 (IL-6) (R = 0.42), and MIP-1α (R = 0.54). Positive correlations were identified between MIP-1α and FGF-basic (R = 0.38), soluble angiopoietin receptor (sTie-2) (R = 0.41), and sVEGFR-1 (R = 0.47).

          Discussion:

          Short-term exposure to lead induces the inflammatory response; however, these mechanisms seem to be different from those observed in chronic lead exposure. Subacute exposure to lead may dysregulate angiogenesis via modifications in the levels of angiogenic factors.

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          Most cited references34

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          Lead Exposure and Cardiovascular Disease—A Systematic Review

          Objective This systematic review evaluates the evidence on the association between lead exposure and cardiovascular end points in human populations. Methods We reviewed all observational studies from database searches and citations regarding lead and cardiovascular end points. Results A positive association of lead exposure with blood pressure has been identified in numerous studies in different settings, including prospective studies and in relatively homogeneous socioeconomic status groups. Several studies have identified a dose–response relationship. Although the magnitude of this association is modest, it may be underestimated by measurement error. The hypertensive effects of lead have been confirmed in experimental models. Beyond hypertension, studies in general populations have identified a positive association of lead exposure with clinical cardiovascular outcomes (cardiovascular, coronary heart disease, and stroke mortality; and peripheral arterial disease), but the number of studies is small. In some studies these associations were observed at blood lead levels < 5 μg/dL. Conclusions We conclude that the evidence is sufficient to infer a causal relationship of lead exposure with hypertension. We conclude that the evidence is suggestive but not sufficient to infer a causal relationship of lead exposure with clinical cardiovascular outcomes. There is also suggestive but insufficient evidence to infer a causal relationship of lead exposure with heart rate variability. Public Health Implications These findings have immediate public health implications. Current occupational safety standards for blood lead must be lowered and a criterion for screening elevated lead exposure needs to be established in adults. Risk assessment and economic analyses of lead exposure impact must include the cardiovascular effects of lead. Finally, regulatory and public health interventions must be developed and implemented to further prevent and reduce lead exposure.
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            Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy.

            Angiogenesis is essential for tumor growth, metastasis, arteriosclerosis as well as embryonic development and wound healing. Its process is dependent on cell proliferation, migration and capillary tube formation in endothelia cells (ECs). High levels of reactive oxygen species (ROS) such as superoxide and H2O2 are observed in various cancer cells. Accumulating evidence suggests that ROS function as signaling molecules to mediate various growth-related responses including angiogenesis. ROS-dependent angiogenesis can be regulated by endogenous antioxidant enzymes such as SOD and thioredoxin. Vascular endothelial growth factor (VEGF), one of the major angiogenesis factor, is induced in growing tumors and stimulates EC proliferation and migration primarily through the VEGF receptor type2 (VEGFR2, Flk1/KDR). Major source of ROS in ECs is a NADPH oxidase which consists of Nox1, Nox2, Nox4, Nox5, p22phox, p47phox and the small G-protein Rac1. NADPH oxidase is activated by various growth factors including VEGF and angiopoietin-1 as well as hypoxia and ischemia, and ROS derived from this oxidase are involved in VEGFR2 autophosphorylation, and diverse redox signaling pathways leading to induction of transcription factors and genes involved in angiogenesis. Dietary antioxidants appear to be effective for treatment of tumor angiogenesis. The aim of this review is to provide an overview of the recent progress on role of ROS derived from NADPH oxidase and redox signaling events involved in angiogenesis. Understanding these mechanisms may provide insight into the NADPH oxidase and redox signaling components as potential therapeutic targets for tumor angiogenesis.
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              Role of angiogenesis in cardiovascular disease: a critical appraisal.

              The role of angiogenesis in atherosclerosis and other cardiovascular diseases has emerged as a major unresolved issue. Angiogenesis has attracted interest from opposite perspectives. Angiogenic cytokine therapy has been widely regarded as an attractive approach both for treating ischemic heart disease and for enhancing arterioprotective functions of the endothelium; conversely, a variety of studies suggest that neovascularization contributes to the growth of atherosclerotic lesions and is a key factor in plaque destabilization leading to rupture. Here, we critically review the evidence supporting a role for angiogenesis and angiogenic factors in atherosclerosis and neointima formation, emphasizing the problems raised by some of the landmark studies and the suitability of animal models of atherosclerosis and neointimal thickening for investigating the role of angiogenesis. Because many of the relevant studies have focused on the role of vascular endothelial growth factor (VEGF), we consider this work in the wider context of VEGF biology and in light of recent experience from clinical trials of VEGF and other angiogenic cytokines for ischemic heart disease. Also discussed are recent findings suggesting that, although angiogenesis may contribute to neointimal growth, it is not required for the initiation of intimal thickening. Our assessment of the evidence leads us to conclude that, although microvessels are a feature of advanced human atherosclerotic plaques, it remains unclear whether angiogenesis either plays a central role in the development of atherosclerosis or is responsible for plaque instability. Furthermore, current evidence from clinical trials of both proangiogenic and antiangiogenic therapies does not suggest that inhibition of angiogenesis is likely to be a viable therapeutic strategy for cardiovascular disease.
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                Author and article information

                Journal
                J Occup Health
                J Occup Health
                Journal of Occupational Health
                Japan Society for Occupational Health
                1341-9145
                1348-9585
                17 August 2018
                20 September 2018
                : 60
                : 5
                : 369-375
                Affiliations
                [1 ] Department of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia
                Author notes
                Correspondence to: A. Machoń-Grecka, Department of Biochemistry, ul. Jordana 19, 41-808 Zabrze, Poland (e-mail: anna.machon-grecka@ 123456med.sum.edu.pl )
                Author information
                https://orcid.org/0000-0002-2395-0477
                Article
                2017-0307-OA
                10.1539/joh.2017-0307-OA
                6176028
                30122729
                a54b1a88-31fa-4ab6-8450-1fb7afdd49fa
                Copyright @

                ©Article author(s). This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. To view the details of this license, please visit ( https://creativecommons.org/licenses/by-nc-sa/4.0/).

                History
                : 2 December 2017
                : 7 May 2018
                Categories
                Original

                angiogenesis,cytokines,inflammation,lead,subacute exposure to lead

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