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Cardiovascular Adaptations to Anemia and the Vascular Endothelium in Sickle Cell Disease Pathophysiology

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Sickle Cell Anemia

Abstract

The vascular endothelium is a heterogenous collection of cells whose actions contribute significantly to sickle cell disease pathophysiology. At the cellular level, the endothelium elaborates vasoactive, adhesive, and inflammatory signals that drive acute and chronic injury causing ultimately irreversible organ damage. The endothelium is also fundamentally involved in the cardiovascular adaptations to anemia. Vasodilation lowers systemic vascular resistance and allows higher cardiac output to maintain oxygen transport in an anemic state. Cardiovascular adaptations to anemia and hypoxia may play a role in the pathogenesis of sickle cell disease. Some measures of endothelium-dependent vasodilation appear to be impaired in people with sickle cell disease, but this may be due in part to the effects of chronic anemia. Endothelium-derived vasoactive molecules, such as endothelin-1 and nitric oxide, appear dysregulated and may also contribute to the vascular complications of sickle cell disease. The therapeutic potential of pharmacologically manipulating these molecules has not yet been achieved; however, evidence from patients treated with hydroxyurea and hematopoietic stem cell transplant shows that although it may be difficult to reverse pre-existing injury, effective therapies for sickle cell disease do change endothelial behavior. Ongoing investigations will determine how best to exploit our understanding of endothelial biology and pathobiology to develop new treatments for people with sickle cell disease.

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Authors and Affiliations

  1. Center for Cancer and Blood Disorders, Children’s National Medical Center, 111 Michigan Ave, NW, Washington, DC, 20010, USA

    Lydia H. Pecker M.D.

  2. Physiology Section, Sickle Cell Branch, National Heart, Lung, and Blood Institute, 10 Center Drive, Bethesda, MD, 20892, USA

    Lydia H. Pecker M.D. & Hans C. Ackerman M.D., D.Phil.

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  1. Lydia H. Pecker M.D.
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  2. Hans C. Ackerman M.D., D.Phil.
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Correspondence to Hans C. Ackerman M.D., D.Phil. .

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  1. Centro de Hematologia e Hemoterapia, Unicamp, Campinas, São Paulo, Brazil

    Fernando Ferreira Costa

  2. Centro de Hematologia e Hemoterapia, Unicamp, Campinas, São Paulo, Brazil

    Nicola Conran

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Pecker, L.H., Ackerman, H.C. (2016). Cardiovascular Adaptations to Anemia and the Vascular Endothelium in Sickle Cell Disease Pathophysiology. In: Costa, F., Conran, N. (eds) Sickle Cell Anemia. Springer, Cham. https://doi.org/10.1007/978-3-319-06713-1_7

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