Redox-dependent impairment of vascular function in sickle cell disease.
The vascular pathophysiology of sickle cell disease (SCD) is influenced by many factors, including adhesiveness of red and white blood cells to endothelium, increased coagulation, and homeostatic perturbation. The vascular endothelium is central to disease pathogenesis because it displays adhesion molecules for blood cells, balances procoagulant and anticoagulant properties of the vessel wall, and regulates vascular homeostasis by synthesizing vasoconstricting and vasodilating substances. The occurrence of intermittent vascular occlusion in SCD leads to reperfusion injury associated with granulocyte accumulation and enhanced production of reactive oxygen species. The participation of nitric oxide (NO) in oxidative reactions causes a reduction in NO bioavailability and contributes to vascular dysfunction in SCD. Therapeutic strategies designed to counteract endothelial, inflammatory, and oxidative abnormalities may reduce the frequency of hospitalization and blood transfusion, the incidence of pain, and the occurrence of acute chest syndrome and pulmonary hypertension in patients with SCD.
Aslan
Mutay
M
Department of Biochemistry, Akdeniz University School of Medicine, 07070 Antalya, Turkey. mutayaslan@akdeniz.edu.tr
Freeman
Bruce A
BA
D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000503:physiopathology*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001682:Biological Availability; D001777:Blood Coagulation / Q000502:physiology; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004912:Erythrocytes / Q000502:physiology; D006451:Hemoglobin, Sickle / Q000187:drug effects / Q000378:metabolism; D006461:Hemolysis / Q000502:physiology; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007962:Leukocytes / Q000502:physiology; D009569:Nitric Oxide / Q000493:pharmacokinetics / Q000502:physiology; D010084:Oxidation-Reduction; D015427:Reperfusion Injury / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D000975:Antioxidants; D006451:Hemoglobin, Sickle; D009569:Nitric Oxide; D006918:Hydroxyurea