Sickle-cell Anemia

Sickle cell anemia (SCA) results in leukocytosis with a chronic pro-inflammatory state. death in patients with SCA may be caused by severe recurrent infections and elevated plasma levels of inflammatory cytokines. SCA is the most common type of hemoglobinopathy. Studies have shown that sickle cell disease (SCD) is characterized by increased hemolysis, leading to plasma heme overload, which induces cardiomyocyte ferroptosis and ultimately cardiovascular complications.

Pathogenesis of Sickle-cell Anemia

In individuals with sickle cell disease, at least one of the β-bead protein subunits of hemoglobin is replaced by hemoglobin S. In sickle cell anemia (also known as pure sickle cell disease), hemoglobin S replaces two β-bead protein subunits in hemoglobin, which is the most common form of sickle cell disease. In other types of sickle cell disease, only one of the β-cadherin subunits in hemoglobin is replaced by hemoglobin S. For example, the hemoglobin molecule of a person with sickle cell disease (HbSC) has hemoglobin S and hemoglobin C instead of hemoglobin β. If the mutations that produce hemoglobin S and β-thalassemia occur together, the individual has hemoglobin S-β-thalassemia.

Pathophysiology, inflammatory stimuli, and cellular interactions in SCA ^[1].

Iron Homeostasis Abnormalities in SCD

The multifaceted pathophysiology triggered by sickle hemoglobin polymer-induced erythrocyte injury includes more generalized cellular and tissue damage caused by hypoxia, oxidative damage, inflammation, abnormal intracellular interactions, and reduced nitric oxide bioavailability, triggering the clinically recognized sickle cell disease.

• Serum Iron Level Change
  Sickle cell patients are characterized by frequent Vaso-occlusive crises and chronic intravascular hemolysis. At the same time, iron released from hemoglobin can be oxidized by H2O2 to form hydroxyl radicals through the Fenton reaction, which increases the level of reactive oxygen species (ROS), leading to protein oxidation, lipid peroxidation and damage to cellular macromolecules and mitochondrial dysfunction. Therefore, elevated iron levels may increase the oxidative burden in sickle cell patients.

• Ferroptosis
  Increased hemolysis in sickle cell disease (SCD) causes heme overload and depletes the heme-scavenging protein hemopexin in the serum. Excess heme causes upregulation of cardiac heme oxygenase 1(Hmox1) that produces free iron, thereby causing cardiac iron overload in SCD. Increased iron promotes free radicals, lipid peroxidation and ultimately ferroptosis in cardiac tissue of SCD. Notably, the ferroptosis inhibitor attenuated cardiomyopathy, whereas the iron death inducer erastin exacerbated cardiac injury in SCD and induced cardiac iron death in non-falciparous mice.

SCD-induced cardiomyocyte ferroptosis ^[1].

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Sickle cell anemia causes abnormalities of oxygen-carrying hemoglobin in the red blood cells, along with abnormal iron homeostasis and complications of cardiovascular disease. Protheragen draws on its research experience in the field of physiological metabolism to help clients conduct in-depth research into sickle cell anemia and the mechanisms that produce it, providing new therapeutic ideas for the disease. If you are interested in the services we offer, please contact us for more information.