| Abstract [eng] |
Angiogenesis and vascular regression are important for the pathogenesis of a number of conditions such as tumors, ischemic diseases and certain ocular diseases. While molecular mechanisms of blood vessel growth have been studied extensively, less is known about blood vessel stability and regression. New blood vessels are stabilized by pericytes – cells of mesenchymal origin that are found in the vessel wall. In the first part of this study, we investigated the molecular mechanism of vessel stabilization by pericytes. We developed a simple in vitro model of pericyte mediated vessel stabilization. In this model, pericytes inhibited regression of vessel-like tubes organized out of endothelial cells. We found that tube association with pericytes in vitro accelerated the metabolism of lysophosphatidic acid (LPA), a vascular regression factor. A drop in the concentration of LPA caused tube stability. Lipid phosphate phosphatase (LPP)-like enzymes were at least in part responsible for the metabolism of LPA. In the second part of this study, we investigated whether autotaxin (ATX) – an enzyme that catalyzes LPA production – is important for vascular regression in vivo. We generated mice with an endothelial cell specific inactivation of Enpp2, the gene that codes for ATX. We determined that ATX produced by endothelial cells was not required for regression of hyaloid vessels or formation of mature retinal vasculature. |
