Angiogenesis in sickle cell disease

Angiogenesis or neovascularization is a global term which indicates the physiological process involving the sprouting of new blood vessels from the pre-existing ones. On the other hand, the development of new blood vessels from differentiating endothelial cells is called vasculogenesis. These processes are vital for tissue development and wound healing in damaged tissues. Sickle cell disease (SCD) is characterized by micro-vascular occlusion with subsequent ischaemia-reperfusion injury, resulting in vasculopathy and organ damage. The vaso-occlusion-induced tissue hypoxia may as well lead to a potent angiogenic response. Angiogenesis is of importance in the pathophysiology of SCD as patients continually experience events of vascular-occlusion. When tissues of SCD patients become infarcted, the rate of tissue regeneration may be dependent on the integrity of angiogenesis, and unbalanced angiogenesis and that could contribute to the development of complications in SCD. The development of new blood vessels is an essential physiological repair process for post-ischaemic tissue restoration in vascular diseases such as SCD. Angiogenesis is a regulated process that requires highly coordinated signaling events, among a variety of angiogenic factors such as angiopoietin-1 (Ang-1), angiopoietin -2 (Ang-2) and vascular endothelial growth factor (VEGF). The normal endothelial cell function depends partly on a carefully regulated balance between angiopoietin-1 (Ang-1) and angiopoietin -2 (Ang-2) that competitively bind to the Tie-2 receptor. Binding of Ang-1, to Tie-2 promotes anti-inflammatory endothelial quiescence and maintenance of vascular integrity. Binding of Ang-2 to Tie-2 on the other hand induces endothelial cell activation and vascular leakage. Angiopoietin-1 and -2 (Ang-1 and Ang-2), which are important regulators of endothelial quiescence and activation, respectively, are deregulated in certain diseases that are associated with endothelial dysfunction such as SCD.