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      Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia

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          Abstract

          Significance: Recent clinical evidence identified anemia to be correlated with severe complications of cardiovascular disease (CVD) such as bleeding, thromboembolic events, stroke, hypertension, arrhythmias, and inflammation, particularly in elderly patients. The underlying mechanisms of these complications are largely unidentified.

          Recent Advances: Previously, red blood cells (RBCs) were considered exclusively as transporters of oxygen and nutrients to the tissues. More recent experimental evidence indicates that RBCs are important interorgan communication systems with additional functions, including participation in control of systemic nitric oxide metabolism, redox regulation, blood rheology, and viscosity. In this article, we aim to revise and discuss the potential impact of these noncanonical functions of RBCs and their dysfunction in the cardiovascular system and in anemia.

          Critical Issues: The mechanistic links between changes of RBC functional properties and cardiovascular complications related to anemia have not been untangled so far.

          Future Directions: To allow a better understanding of the complications associated with anemia in CVD, basic and translational science studies should be focused on identifying the role of noncanonical functions of RBCs in the cardiovascular system and on defining intrinsic and/or systemic dysfunction of RBCs in anemia and its relationship to CVD both in animal models and clinical settings. Antioxid. Redox Signal. 26, 718–742.

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          Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia.

          Jack Guralnik, Richard Eisenstaedt, Luigi Ferrucci … (2004)
          Clinicians frequently identify anemia in their older patients, but national data on the prevalence and causes of anemia in this population in the United States have been unavailable. Data presented here are from the noninstitutionalized US population assessed in the third National Health and Nutrition Examination Survey (1988-1994). Anemia was defined by World Health Organization criteria; causes of anemia included iron, folate, and B(12) deficiencies, renal insufficiency, anemia of chronic inflammation (ACI), formerly termed anemia of chronic disease, and unexplained anemia (UA). ACI by definition required normal iron stores with low circulating iron (less than 60 microg/dL). After age 50 years, anemia prevalence rates rose rapidly, to a rate greater than 20% at age 85 and older. Overall, 11.0% of men and 10.2% of women 65 years and older were anemic. Of older persons with anemia, evidence of nutrient deficiency was present in one third, ACI or chronic renal disease or both was present in one third, and UA was present in one third. Most occurrences of anemia were mild; 2.8% of women and 1.6% of men had hemoglobin levels lower than 110 g/L (11 g/dL). Therefore, anemia is common, albeit not severe, in the older population, and a substantial proportion of anemia is of indeterminate cause. The impact of anemia on quality of life, recovery from illness, and functional abilities must be further investigated in older persons.
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            Red cell membrane: past, present, and future.

            Narla Mohandas, Patrick Gallagher (2008)
            As a result of natural selection driven by severe forms of malaria, 1 in 6 humans in the world, more than 1 billion people, are affected by red cell abnormalities, making them the most common of the inherited disorders. The non-nucleated red cell is unique among human cell type in that the plasma membrane, its only structural component, accounts for all of its diverse antigenic, transport, and mechanical characteristics. Our current concept of the red cell membrane envisions it as a composite structure in which a membrane envelope composed of cholesterol and phospholipids is secured to an elastic network of skeletal proteins via transmembrane proteins. Structural and functional characterization of the many constituents of the red cell membrane, in conjunction with biophysical and physiologic studies, has led to detailed description of the way in which the remarkable mechanical properties and other important characteristics of the red cells arise, and of the manner in which they fail in disease states. Current studies in this very active and exciting field are continuing to produce new and unexpected revelations on the function of the red cell membrane and thus of the cell in health and disease, and shed new light on membrane function in other diverse cell types.
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              Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score.

              Sumeet Subherwal, Richard Bach, Anita Chen … (2009)
              Treatments for non-ST-segment-elevation myocardial infarction (NSTEMI) reduce ischemic events but increase bleeding. Baseline prediction of bleeding risk can complement ischemic risk prediction for optimization of NSTEMI care; however, existing models are not well suited for this purpose. We developed (n=71 277) and validated (n=17 857) a model that identifies 8 independent baseline predictors of in-hospital major bleeding among community-treated NSTEMI patients enrolled in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) Quality Improvement Initiative. Model performance was tested by c statistics in the derivation and validation cohorts and according to postadmission treatment (ie, invasive and antithrombotic therapy). The CRUSADE bleeding score (range 1 to 100 points) was created by assignment of weighted integers that corresponded to the coefficient of each variable. The rate of major bleeding increased by bleeding risk score quintiles: 3.1% for those at very low risk (score 50; P(trend) or = 2 antithrombotics=0.72; <2 antithrombotics=0.73; invasive approach=0.73; conservative approach=0.68. The CRUSADE bleeding score quantifies risk for in-hospital major bleeding across all postadmission treatments, which enhances baseline risk assessment for NSTEMI care.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Antioxid Redox Signal
                Journal ID (iso-abbrev): Antioxid. Redox Signal
                Journal ID (publisher-id): ars
                Title: Antioxidants & Redox Signaling
                Publisher: Mary Ann Liebert, Inc. (140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA )
                ISSN (Print): 1523-0864
                ISSN (Electronic): 1557-7716
                Publication date (Print): 01 May 2017
                Publication date (Electronic): 01 May 2017
                Publication date PMC-release: 01 May 2017
                Volume: 26
                Issue: 13
                Pages: 718-742
                Affiliations
                [ 1 ]Cardiovascular Research Laboratory, Division of Cardiology, Pneumology, and Vascular Medicine, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany.
                [ 2 ]Department of Molecular Physiology and Biological Physics, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine , Charlottesville, Virginia.
                Author notes
                [*]

                These authors contributed equally to this work.

                Address correspondence to: Dr. Miriam M. Cortese-Krott, Cardiovascular Research Laboratory, Division of Cardiology, Pneumology, and Vascular Medicine, Medical Faculty, Heinrich Heine University of Düsseldorf Moorenstr. 5, Düsseldorf 40225, Germany

                E-mail: miriam.cortese@ 123456uni-duesseldorf.de
                Article
                Publisher ID: 10.1089/ars.2016.6954
                DOI: 10.1089/ars.2016.6954
                PMC ID: 5421513
                PubMed ID: 27889956
                SO-VID: ab91a248-3edb-4d1a-bd20-a01d53f4da12
                Copyright © © Viktoria Kuhn, et al., 2017; Published by Mary Ann Liebert, Inc.
                License:

                This Open Access article is distributed under the terms of the Creative Commons License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                Date received : 20 November 2016
                Date accepted : 25 November 2016
                Page count
                Figures: 6, Tables: 1, Equations: 19, References: 200, Pages: 25
                Categories
                Subject: Forum Review Articles

                Cardiovascular - Part II (J. Haendeler, Ed.)

                Keywords: red blood cells,nitric oxide,anemia,rbc deformability,hemolysis,cardiovascular disease,red cell enos
                Data availability:
                Keywords: red blood cells, nitric oxide, anemia, rbc deformability, hemolysis, cardiovascular disease, red cell enos

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