CXCL12 enhances angiogenesis through CXCR7 activation in human umbilical vein endothelial cells

Abstract

Angiogenesis is the process by which new vessels form from existing vascular networks. Human umbilical vein endothelial cells (HUVECs) may contribute to the study of vascular repair and angiogenesis. The chemokine CXCL12 regulates multiple cell functions, including angiogenesis, mainly through its receptor CXCR4. In contrast to CXCL12/CXCR4, few studies have described roles for CXCR7 in vascular biology, and the downstream mechanism of CXCR7 in angiogenesis remains unclear. The results of the present study showed that CXCL12 dose-dependently enhanced angiogenesis in chorioallantoic membranes (CAMs) and HUVECs. The specific activation of CXCR7 with TC14012 (a CXCR7 agonist) resulted in the significant induction of tube formation in HUVECs and in vivo. Further evidence suggested that CXCL12 induced directional polarization and migration in the HUVECs, which is necessary for tube formation. Moreover, CXCR7 translocalization was observed during the polarization of HUVECs in stripe assays. Finally, treatment with TC14012 also significantly increased PI3K/Akt phosphorylation, and tube formation was blocked by treating HUVECs with an Akt inhibitor. Overall, this study indicated that CXCL12-stimulated CXCR7 acts as a functional receptor to activate Akt for angiogenesis in HUVECs and that CXCR7 may be a potential target molecule for endothelial regeneration and repair after vascular injury.

CXCR4 or CXCR7 antagonists treat endometriosis by reducing bone marrow cell trafficking

“…The CXCL12‐CXC4‐CXCR7 axis has a crucial role in vascular remodelling and endothelial function, including angiogenesis and vasculogenesis, and both processes have been also described in murine endometriosis . AMD3100 and CCX771 have been described as potent anti‐angiogenesis drugs .…”

“…58 Similarly, aberrant oestrogen signalling and progesterone resistance further amplified CXCL12-CXCR4 axis activation in endometrial cells and endometriosis. 45,46 Targeting CXCR4 or CXCR7 using AMD3100 or 59,60 and both processes have been also described in murine endometriosis. 44 AMD3100 and CCX771 have been described as potent anti-angiogenesis drugs.…”

The bifunctional SDF‐1‐AnxA5 fusion protein protects cardiac function after myocardial infarction

“…Neovascularization is an essential mechanism underlying myocardial repair. SDF‐1 is also known as a major angiogenic protein . To determine whether SDF‐1‐AnxA5 have the proangiogenic capability, we performed an endothelial cell in vitro tube formation assay which is a powerful in vitro method to screen angiogenic factors .…”

“…SDF-1 is also known as a major angiogenic protein. 17 To determine whether SDF-1-AnxA5 have the proangiogenic F I G U R E 1 The preparation of native stromal cell-derived factor-1 (SDF-1), AnxA5 and SDF-1-Annexin. A, Schematic illustration of SDF-1-AnxA5 sequence.…”

An update on angiogenesis modulators with a potential therapeutic role

“…Remarkable, SDF-1/ CXCL12 complex has a unidirectional chemoattractant action in HUVECs. It seems that CXCR7 action is facilitated by the PI3K/Akt phosphorylation pathway suggesting that SDF-1/ CXCR7 represents a complex receptor for Aktinduced angiogenesis [15].…”