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      Myeloperoxidase: a new target for the treatment of stroke?

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          Abstract

          Myeloperoxidase is an important inflammatory factor in the myeloid system, primarily expressed in neutrophils and microglia. Myeloperoxidase and its active products participate in the occurrence and development of hemorrhagic and ischemic stroke, including damage to the blood-brain barrier and brain. As a specific inflammatory marker, myeloperoxidase can be used in the evaluation of vascular disease occurrence and development in stroke, and a large amount of experimental and clinical data has indicated that the inhibition or lack of myeloperoxidase has positive impacts on stroke prognosis. Many studies have also shown that there is a correlation between the overexpression of myeloperoxidase and the risk of stroke. The occurrence of stroke not only refers to the first occurrence but also includes recurrence. Therefore, myeloperoxidase is significant for the clinical evaluation and prognosis of stroke. This paper reviews the potential role played by myeloperoxidase in the development of vascular injury and secondary brain injury after stroke and explores the effects of inhibiting myeloperoxidase on stroke prognosis. This paper also analyzes the significance of myeloperoxidase etiology in the occurrence and development of stroke and discusses whether myeloperoxidase can be used as a target for the treatment and prediction of stroke.

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          The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology.

          For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the phagocyte NADPH oxidase itself (NOX2/gp91(phox)), the homologs are now referred to as the NOX family of NADPH oxidases. These enzymes share the capacity to transport electrons across the plasma membrane and to generate superoxide and other downstream reactive oxygen species (ROS). Activation mechanisms and tissue distribution of the different members of the family are markedly different. The physiological functions of NOX family enzymes include host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. NOX enzymes also contribute to a wide range of pathological processes. NOX deficiency may lead to immunosuppresion, lack of otoconogenesis, or hypothyroidism. Increased NOX activity also contributes to a large number or pathologies, in particular cardiovascular diseases and neurodegeneration. This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.
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            GLOBAL, REGIONAL, AND COUNTRY-SPECIFIC LIFETIME RISK OF STROKE, 1990–2016

            Background Lifetime stroke risk has been calculated in a limited number of selected populations. We determined lifetime risk of stroke globally and at the regional and country level. Methods Using Global Burden of Disease Study estimates of stroke incidence and the competing risks of non-stroke mortality, we estimated the cumulative lifetime risk of ischemic stroke, hemorrhagic stroke, and total stroke (with 95% uncertainty intervals [UI]) for 195 countries among adults over 25 years) for the years 1990 and 2016 and according to the GBD Study Socio-Demographic Index (SDI). Results The global estimated lifetime risk of stroke from age 25 onward was 24.9% (95% UI: 23.5–26.2): 24.7% (23.3–26.0) in men and 25.1% (23.7–26.5) in women. The lifetime risk of ischemic stroke was 18.3% and of hemorrhagic stroke was 8.2%. The risk of stroke was 23.5% in high SDI countries, 31.1% in high-middle SDI countries, and 13.2% in low SDI countries with UIs not overlapping for these categories. The greatest estimated risk of stroke was in East Asia (38.8%) and Central and Eastern Europe (31.7 and 31.6 %%), and lowest in Eastern Sub-Saharan Africa (11.8%). From 1990 to 2016, there was a relative increase of 8.9% in global lifetime risk. Conclusions The global lifetime risk of stroke is approximately 25% starting at age 25 in both men and women. There is geographical variation in the lifetime risk of stroke, with particularly high risk in East Asia, Central and Eastern Europe.
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              Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation

              Peripheral blood neutrophils form highly decondensed chromatin structures, termed neutrophil extracellular traps (NETs), that have been implicated in innate immune response to bacterial infection. Neutrophils express high levels of peptidylarginine deiminase 4 (PAD4), which catalyzes histone citrullination. However, whether PAD4 or histone citrullination plays a role in chromatin structure in neutrophils is unclear. In this study, we show that the hypercitrullination of histones by PAD4 mediates chromatin decondensation. Histone hypercitrullination is detected on highly decondensed chromatin in HL-60 granulocytes and blood neutrophils. The inhibition of PAD4 decreases histone hypercitrullination and the formation of NET-like structures, whereas PAD4 treatment of HL-60 cells facilitates these processes. The loss of heterochromatin and multilobular nuclear structures is detected in HL-60 granulocytes after PAD4 activation. Importantly, citrullination of biochemically defined avian nucleosome arrays inhibits their compaction by the linker histone H5 to form higher order chromatin structures. Together, these results suggest that histone hypercitrullination has important functions in chromatin decondensation in granulocytes/neutrophils.
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                Author and article information

                Journal
                Neural Regen Res
                Neural Regen Res
                NRR
                Neural Regeneration Research
                Wolters Kluwer - Medknow (India )
                1673-5374
                1876-7958
                August 2022
                07 January 2022
                : 17
                : 8
                : 1711-1716
                Affiliations
                [1 ]The Second Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, China
                [2 ]Department of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China
                [3 ]Xiangya Hospital, Central South University, Changsha, Hunan Province, China
                [4 ]Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
                [5 ]University of Chinese Academy of Sciences, Beijing, China
                Author notes
                [* ] Correspondence to: Yi-Nian Zhang, ery_zhangyinian@ 123456lzu.edu.cn ; Ya-Wen Pan, panyawen666@ 123456sohu.com .

                Author contributions: Literature search: YCW, YBL; manuscript writing: YCW, YBL, XLH, YFL, LZ, JY, MS, HLM; manuscript revision: XLH, YFL, LZ, JY, MS, HLM, YWP, YNZ. All authors read and approved the final manuscript .

                [#]

                Both authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-3518-7154
                https://orcid.org/0000-0003-4375-8316
                Article
                NRR-17-1711
                10.4103/1673-5374.332130
                8820716
                35017418
                39a3a7ba-7c70-400c-be87-edbcc6018e1c
                Copyright: © Neural Regeneration Research

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 25 January 2021
                : 22 March 2021
                : 23 August 2021
                Categories
                Review

                blood-brain barrier,hemorrhagic stroke,inflammation,ischemic stroke,microglia,myeloperoxidase,neutrophils,secondary brain injury,stroke

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