Pericytes prevent regression of endothelial cell tubes by accelerating metabolism of lysophosphatidic acid.

ABSTRACT

Efforts to eradicate pathological vessels in neovascular diseases and induce growth of mature, functional vasculature in ischemic diseases are limited by our incomplete understanding of molecular mechanisms of vessel stabilization. While it is well known that pericytes stabilize blood vessels, the underlying mechanisms have not been fully elucidated. The goal of this study was to further investigate the mechanisms by which pericytes stabilize vessels. In an in vitro model of blood vessels, in which regression is driven by lysophosphatidic acid (LPA), pericyte-mediated stabilization was associated with a decrease in the concentration of LPA. The decline in the concentration of LPA was not caused by a reduction in activity or expression of autotaxin, the main enzyme implicated in LPA production. Rather, pericytes accelerated LPA metabolism. Stabilization of tubes by pericytes correlated with accelerated LPA dephosphorylation and increased expression of lipid phosphate phosphatases (LPPs). Finally, pericytes failed to stabilize tubes exposed to an LPA analogue, which was resistant to degradation. Our results suggest that pericytes stabilize endothelial cell tubes by accelerating the metabolism of LPA.