Am J Pathol 184:556 (2014)

Circulating Fibrocytes Stabilize Blood Vessels during Angiogenesis in a Paracrine Manner.

Li J1, Tan H2, Wang X3, Li Y3, Samuelson L4, Li X5, Cui C4, Gerber DA4.


Accumulating evidence supports that circulating fibrocytes play important roles in
angiogenesis. However, the specific role of fibrocytes in angiogenesis and the underlying
mechanisms remain unclear. In this study, we found that fibrocytes stabilized newly formed
blood vessels in a mouse wound-healing model by inhibiting angiogenesis during the
proliferative phase and inhibiting blood vessel regression during the remodeling phase.
Fibrocytes also inhibited angiogenesis in a Matrigel mouse model. In vitro study showed that
fibrocytes inhibited both the apoptosis and proliferation of vascular endothelial cells (VECs)
in a permeable support (Transwell) co-culture system. In a three-dimensional collagen gel,
fibrocytes stabilized the VEC tubes by decreasing VEC tube density on stimulation with growth
factors and preventing VEC tube regression on withdrawal of growth factors. Further
mechanistic investigation revealed that fibrocytes expressed many prosurvival factors that are
responsible for the prosurvival effect of fibrocytes on VECs and blood vessels. Fibrocytes
also expressed angiogenesis inhibitors, including thrombospondin-1 (THBS1). THBS1 knockdown
partially blocked the fibrocyte-induced inhibition of VEC proliferation in the Transwell co-
culture system and recovered the fibrocyte-induced decrease of VEC tube density in collagen
gel. Purified fibrocytes transfected with THBS1 siRNA partially recovered the fibrocyte-
induced inhibition of angiogenesis in both the wound-healing and Matrigel models. In
conclusion, our findings reveal that fibrocytes stabilize blood vessels via prosurvival
factors and anti-angiogenic factors, including THBS1.

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