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      Evaluation of endothelial microparticles as a prognostic marker in hemolytic disease of the newborn in China

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          Abstract

          Objective

          This study aimed to evaluate endothelial microparticles (EMPs) as a potential prognostic marker in hemolytic disease of the Chinese neonate.

          Methods

          We compared 29 newborns with ABO hemolytic disease of the newborn (ABO HDN), 22 newborns with Rh HDN, and 21 healthy newborns with matched mother and infant blood groups (controls). Markers of hemolysis and von Willebrand factor antigen (vWF Ag) were analyzed. EMP (CD144+) levels were measured before and after therapy.

          Results

          vWF Ag and pretherapy EMP levels were higher in the ABO HDN and Rh HDN groups than in the control group. Additionally, vWF Ag and pretherapy EMP levels were significantly higher in the ABO HDN group than in the Rh HDN group. Posttherapy EMP levels were decreased compared with pretherapy levels in the ABO HDN and Rh HDN groups. Moreover, hemoglobin and indirect bilirubin levels were independently correlated with pretherapy EMP levels in the ABO HDN group.

          Conclusion

          Our findings indicate that EMP measurement in neonates with HDN may provide a novel method of monitoring possible severe vascular dysfunction in patients in China. An external validation in larger datasets is necessary for further study.

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          Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure.

          Ken Nguyen, Scott Boulanger, Ziad Mallat … (2005)
          Endothelial dysfunction and arterial stiffness are major determinants of cardiovascular risk in patients with end-stage renal failure (ESRF). Microparticles are membrane fragments shed from damaged or activated cells. Because microparticles can affect endothelial cells, this study investigated the relationship between circulating microparticles and arterial dysfunction in patients with ESRF and identified the cellular origin of microparticles associated with these alterations. Flow cytometry analysis of platelet-free plasma from 44 patients with ESRF indicated that circulating levels of Annexin V+ microparticles were increased compared with 32 healthy subjects, as were levels of microparticles derived from endothelial cells (three-fold), platelets (16.5-fold), and erythrocytes (1.6-fold). However, when arterial function was evaluated noninvasively in patients with ESRF, only endothelial microparticle levels correlated highly with loss of flow-mediated dilation (r = -0.543; P = 0.004), increased aortic pulse wave velocity (r = 0.642, P < 0.0001), and increased common carotid artery augmentation index (r = 0.463, P = 0.0017), whereas platelet-derived, erythrocyte-derived, and Annexin V+ microparticle levels did not. In vitro, microparticles from patients with ESRF impaired endothelium-dependent relaxations and cyclic guanosine monophosphate generation, whereas microparticles from healthy subjects did not. Moreover, in vitro endothelial dysfunction correlated with endothelial-derived (r = 0.891; P = 0.003) but not platelet-derived microparticle concentrations. In fact, endothelial microparticles alone decreased endothelial nitric oxide release by 59 +/- 7% (P = 0.025). This study suggests that circulating microparticles of endothelial origin are tightly associated with endothelial dysfunction and arterial dysfunction in ESRF.
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            Cell-derived microparticles in haemostasis and vascular medicine.

            Laurent Burnier, Pierre Fontana, Brenda R Kwak … (2009)
            Considerable interest for cell-derived microparticles has emerged, pointing out their essential role in haemostatic response and their potential as disease markers, but also their implication in a wide range of physiological and pathological processes. They derive from different cell types including platelets - the main source of microparticles - but also from red blood cells, leukocytes and endothelial cells, and they circulate in blood. Despite difficulties encountered in analyzing them and disparities of results obtained with a wide range of methods, microparticle generation processes are now better understood. However, a generally admitted definition of microparticles is currently lacking. For all these reasons we decided to review the literature regarding microparticles in their widest definition, including ectosomes and exosomes, and to focus mainly on their role in haemostasis and vascular medicine.
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              Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease.

              Seigo Sugiyama, Hideaki Jinnouchi, H Fukushima … (2005)
              The purpose of this study was to examine whether CD144-EMP (endothelium-derived microparticles) is useful as a specific marker of endothelial cell (EC) dysfunction and to determine whether plasma levels of circulating CD144-EMP predicted coronary artery disease (CAD) in patients with type 2 diabetes mellitus (DM). Endothelial cell dysfunction is involved in atherogenesis; however, the quantitative assessment of EC dysfunction has yet to be established clinically. Endothelium-derived microparticles are small, membrane-shed vesicles that are generated from the EC surface in response to cellular dysfunction and/or injury. Diabetes mellitus is known to be associated with EC dysfunction and accelerated atherosclerosis. We characterized EMP using anti-CD144 (VE-Cadherin) antibody in various atherosclerosis-related cells and investigated the association between the levels of CD144-positive microparticles and hydrogen-peroxide-induced EC injury and acetylcholine-induced coronary vasomotion. Furthermore, we evaluated plasma CD144-EMP levels in patients with and without DM. We demonstrated that CD144-positive microparticles were derived selectively from human EC. The levels of CD144-EMP reflected the degree of in vitro hydrogen-peroxide-induced EC injury and impairment of in vivo endothelium-dependent coronary vasodilation (p < 0.01). Plasma CD144-EMP levels were increased significantly in DM patients compared with patients without DM (p < 0.001). In DM patients, the elevated levels of CD144-EMP were the most significant risk factor for CAD relative to all other traditional risk factors (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8 to 6.9, p < 0.001). Notably, plasma CD144-EMP identified a subpopulation of established CAD patients in DM subjects without typical anginal symptoms (OR 10.6, 95% CI 3.9 to 29.5, p < 0.001). The CD144-positive EMP exist in human plasma, and plasma CD144-EMP levels can be a clinically specific and quantitative marker of EC dysfunction and/or injury. Measurement of CD144-EMP, by providing a quantitative assessment of EC dysfunction, may be useful for identifying DM patients with increased risk of CAD.
              Article 0 comments Cited 92 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Int Med Res
                Journal ID (iso-abbrev): J. Int. Med. Res
                Journal ID (publisher-id): IMR
                Journal ID (hwp): spimr
                Title: The Journal of International Medical Research
                Publisher: SAGE Publications (Sage UK: London, England )
                ISSN (Print): 0300-0605
                ISSN (Electronic): 1473-2300
                Publication date (Electronic): 13 September 2019
                Publication date (Print): November 2019
                Volume: 47
                Issue: 11
                Pages: 5732-5739
                Affiliations
                [1-0300060519870947]Department of Pediatrics, Baoding First Central Hospital, Baoding, Hebei, China
                Author notes
                [*]Xiao-jing Zhu, Department of Pediatrics, Baoding First Central Hospital, No. 320 North Street, Great Wall, Baoding 071000, Hebei, China. Email: tqe990@ 123456163.com
                Author information
                https://orcid.org/0000-0003-0628-8810
                Article
                Publisher ID: 10.1177_0300060519870947
                DOI: 10.1177/0300060519870947
                PMC ID: 6862913
                PubMed ID: 31516072
                SO-VID: 38f80a50-d3a7-463c-9f7a-cbd2d3139971
                Copyright © © The Author(s) 2019
                License:

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 11 April 2019
                Date accepted : 30 July 2019
                Categories
                Subject: Pre-Clinical Research Reports

                Keywords: endothelial microparticles (emps),hemolytic disease of the newborn (hdn),abo hdn,von willebrand factor antigen,hemoglobin,bilirubin
                Data availability:
                Keywords: endothelial microparticles (emps), hemolytic disease of the newborn (hdn), abo hdn, von willebrand factor antigen, hemoglobin, bilirubin

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