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(Circulation Research. 2003;93:274.)
© 2003 American Heart Association, Inc.

Editorials

T-Type Calcium Current in Sickle Cell Disease

A Channel to Therapy?

Anthony Varghese, Edward Kenneth Weir

From the Division of Cardiology (E.K.W.), Veterans Affairs Medical Center, Minneapolis, Minn; Department of Medicine (A.V., E.K.W.), University of Minnesota, Minneapolis, Minn.

Correspondence to E.K. Weir, MD, Cardiology (111 C), Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417. E-mail weirx002@umn.edu

Key Words: sickle cell disease • calcium channels • thrombin

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In 1910, James Herrick made the first report of a case of sickle cell anemia.¹ He described thin, elongated, sickle-shaped, and crescent-shaped red blood corpuscles. Soon afterward, the observation of sickle cells in the asymptomatic father of a sickle cell anemia patient raised the possibility of an inherited disorder.² The distinction between symptomatic sickle cell anemia and the asymptomatic sickle cell trait was established in 1933.³ The difference between normal hemoglobin (HbAA) and sickle hemoglobin (HbSS) was recognized in 1959 to be the substitution of a valine residue for a glutamic acid in the ß-chain amino terminus.⁴ Patients who have the sickle cell trait are heterozygotes (HbAS), having an abnormal, as well as a normal, ß-globin gene. In sickle cell anemia, sickling may start at an oxygen saturation as high as 85%, while in the trait the desaturation has to be more severe before sickling is induced.

Sickling leading to vaso-occlusion and infarction occurs in many organs but was first described in the lungs.⁵ Initially it was thought that deformation and increased rigidity of the erythrocytes, related to polymerization of HbSS, was sufficient to cause mechanical obstruction. However, the work of Hebbel et al^6,7 focused attention on erythrocyte adherence to the endothelium as a mechanism promoting microvascular occlusion. A key observation in this regard is that sickle erythrocytes adhere more readily to microvascular endothelium than to endothelium from conduit vessels.⁸ If endothelial cells circulating in the blood can be taken as representative of the sedentary population, the endothelium is activated . . . [Full Text of this Article]

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