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      Association between vascular access failure and microparticles in hemodialysis patients

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          Abstract

          Background

          Vascular access failure, a major cause of morbidity in hemodialysis (HD) patients, occurs mainly at stenotic endothelium following an acute thrombotic event. Microparticles (MPs) are fragments derived from injured cell membrane and are closely associated with coagulation and vascular inflammatory responses.

          Methods

          We investigated the relationship between levels of circulating MPs and vascular access patency in HD patients. A total of 82 HD patients and 28 healthy patients were enrolled. We used flow cytometry to measure endothelial MPs (EMPs) identified by CD31+CD42− or CD51+ and platelet-derived MPs (PMPs) identified by CD31+CD42+ in plasma samples of participants. Vascular access patency was defined as an interval from the time of access formation to the time of first access stenosis in each patient. MP counts were compared according to access patent duration.

          Results

          The levels of EMP (both CD31+CD42− and CD51+) and CD31+CD42+PMP were significantly higher in patients than in healthy participants. Levels of CD31+CD42−EMP and CD31+CD42+PMP showed a positive correlation. In non-diabetic HD patients, CD31+CD42−EMPs and CD31+CD42+PMPs were more elevated in the shorter access survival group (access survival <1 year) than in the longer survival group (access survival ≥ 4 years).

          Conclusion

          Elevated circulating EMP or PMP counts are influenced by end-stage renal disease and increased levels of EMP and PMP may be associated with vascular access failure in HD patients.

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          Most cited references33

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

          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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            Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes.

            Apoptotic microparticles are responsible for almost all tissue factor activity of the plaque lipid core. We hypothesized that elevated levels of procoagulant microparticles could also circulate in the peripheral blood of patients with recent clinical signs of plaque disruption and thrombosis. We studied 39 patients with coronary heart disease, including 12 patients with stable angina and 27 patients with acute coronary syndromes (ACS), and 12 patients with noncoronary heart disease. We isolated the circulating microparticles by capture with annexin V and determined their procoagulant potential with a prothrombinase assay. The cell origins of microparticles were determined in an additional 22 patients by antigenic capture with specific antibodies. The level of procoagulant microparticles did not differ between stable angina patients and noncoronary patients (10.1+/-1.6 nmol/L phosphatidylserine [PS] equivalent versus 9.9+/-1.6 nmol/L PS equivalent, respectively). However, procoagulant microparticles were significantly elevated in patients with ACS (22.2+/-2.7 nmol/L PS equivalent) compared with other coronary (P<0.01) or noncoronary (P<0.01) patients. Microparticles of endothelial origin were significantly elevated in patients with ACS (P<0.01), which suggests an important role for endothelial injury in inducing the procoagulant potential. High levels of procoagulant endothelial microparticles are present in the circulating blood of patients with ACS and may contribute to the generation and perpetuation of intracoronary thrombi.
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              Hemodialysis vascular access dysfunction: a cellular and molecular viewpoint.

              Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population. The major cause of hemodialysis vascular access dysfunction is venous stenosis as a result of neointimal hyperplasia. Despite the magnitude of the clinical problem, however, there has been a paucity of novel therapeutic interventions in this field. This is in marked contrast to a recent plethora of targeted interventions for the treatment of arterial neointimal hyperplasia after coronary angioplasty. The reasons for this are two-fold. First there has been a relative lack of cellular and molecular research that focuses on venous neointimal hyperplasia in the specific setting of hemodialysis vascular access. Second, there have been inadequate efforts by the nephrology community to translate the recent advances in molecular and interventional cardiology into therapies for hemodialysis vascular access. This review therefore (1) briefly examines the different forms of hemodialysis vascular access that are available, (2) describes the pathology and pathogenesis of hemodialysis vascular access dysfunction in both polytetrafluoroethylene grafts and native arteriovenous fistulae, (3) reviews recent concepts about the pathogenesis of vascular stenosis that could potentially be applied in the setting of hemodialysis vascular access dysfunction, (4) summarizes novel experimental and clinical therapies that could potentially be used in the setting of hemodialysis vascular access dysfunction, and, finally, (5) offers some broad guidelines for future innovative translational and clinical research in this area that hopefully will reduce the huge clinical morbidity and economic costs that are associated with this condition.
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                Author and article information

                Contributors
                Journal
                Kidney Res Clin Pract
                Kidney Res Clin Pract
                Kidney Research and Clinical Practice
                Elsevier
                2211-9132
                2211-9140
                06 January 2012
                March 2012
                06 January 2012
                : 31
                : 1
                : 38-47
                Affiliations
                [1 ]Division of Nephrology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
                [2 ]Medical Research Institute, Ewha Womans University School of Medicine, Seoul, Korea
                Author notes
                [* ]Corresponding author. Division of Nephrology, Ewha Womans University Mokdong Hospital, 911-1, Mok-dong, Yangcheon-gu, Seoul, 158-710, Korea. sjkimwon@ 123456ewha.ac.kr
                Article
                S2211-9132(11)00003-9
                10.1016/j.krcp.2011.12.002
                4715093
                26889407
                2844c358-0492-481a-b41b-bcf571be3f45
                © 2012. The Korean Society of Nephrology. Published by Elsevier.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 26 April 2011
                : 10 July 2011
                : 3 August 2011
                Categories
                Original Article

                cell derived,endothelial cells,hemodialysis,microparticles,platelets,vascular access failure

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