Angiogenesis, the formation, and organization of new blood vessels from the preexisting vasculature, contributes to physiological and pathologic changes in vascular structure and is tightly controlled by a variety of angiogenic and antiangiogenic factors.
1 Depending on the physiological or pathologic context, angiogenesis can be beneficial, such as in collateral formation in ischemic disease states,
2 or detrimental, as in diabetic retinopathy.
3 Several mediators induce angiogenesis, including members of the fibroblast growth factor (FGF) family,
4 vascular endothelial growth factor (VEGF),
5 epidermal growth factor (EGF),
6 tumor necrosis factor (TNF-α),
7 and certain members of the CXC chemokine family.
8 One of the factors that potentially contributes to the development and progression of diabetic vascular alterations is stromal cell–derived factor (SDF)-1α.
9 SDF-1α is a highly efficient chemotactic factor for T cells,
10 monocytes,
11 pre-B-cells,
12 dendritic cells,
13 and hematopoietic progenitor cells.
14 SDF-1α mediates its cellular effects such as Ca
2+ mobilization, cell migration, and angiogenesis mainly by binding to its chemokine receptor (CXCR)-4. Although SDF-1α binds to other receptors such as CXCR7, ligand activation of CXCR7 does not cause Ca
2+ mobilization or cell migration.
15 SDF-1α is the predominant chemokine that mobilizes HSCs and EPCs.
16 SDF-1α has been shown to be upregulated in many damaged tissues as part of the injury response and is thought to call stem and progenitor cells to promote repair.
17 In vasculature, SDF-1α functions as a potent inducer of angiogenesis, where it stimulates endothelial cells proliferation and cell survival through activation of the endothelial cell receptor.
18 SDF-1α levels are increased in diabetic subjects with proliferative diabetic retinopathy (PDR).
19 Although migration of endothelial cells is one of the important components of the angiogenic processes, little is known about the mechanisms of SDF-1α–induced human retinal endothelial cell migration and the chemotactic signaling pathways involved. Curcumin (diferuloylmethane), the main bioactive component of turmeric, has been shown to have antiangiogenic properties.
20 We have shown that curcumin inhibits human retinal endothelial cell proliferation.
21 However, this is the first study to investigate the role of SDF-1α in HREC migration, the chemotactic signaling pathways involved, and effect of the curcumin on HREC migration.