New Insights Regarding Vessel Regression

Phospholipase Cγ Activation Drives Increased Production of Autotaxin in Endothelial Cells and Lysophosphatidic Acid-Dependent Regression

“…Pathological vessels in tumors and within numerous ocular beds undergo at least partial regression in response to anti-VEGF therapy (5). Regression can also be induced by the microenvironment of the vasculature, and this information can come in the form of soluble factors that are produced by other cell types (13). Thus, there appear to be multiple ways to induce regression of vessels; this information is likely to guide efforts to enhance current antiangiogenic therapies.…”

The Bipartite Rac1 Guanine Nucleotide Exchange Factor Engulfment and Cell Motility 1/Dedicator of Cytokinesis 180 (Elmo1/Dock180) Protects Endothelial Cells from Apoptosis in Blood Vessel Development

“…However, at later stages vascular expression of Elmo1 diminishes, which suggested a specific and transient function in early processes of vascular development (35). During angiogenesis, newly formed blood vessels require stabilizing and survival factors, otherwise they are prone to apoptosis and vessel regression (3)(4)(5)(6)(7)9). Elmo1 expression in the zebrafish vasculature (35), its protective function in cultured ECs and its pro-survival function in zebrafish embryos suggest that Elmo1 and its complex partner Dock180 stabilize newly formed blood vessels.…”

“…Pruning or vessel regression is an active, tightly controlled process due to changes in hemodynamics and includes endothelial cell-cell contact reorganization, cell retraction and induction of apoptosis (3)(4)(5)(6)(7). The decision whether a newly formed vessel remains or undergoes pruning is made by several factors, such as survival factors, establishment and stabilization of cell-cell contacts, either of ECs or pericytes, deposition of basal membrane, and initiation of blood flow (1,8,9). Particularly, ECs are dependent on survival and stabilization factors like VEGF, delta-like ligand 4 (Dll4), fibroblast growth factor (FGF), or angiopoietin-1 (Ang-1) to prevent vessel regression (6, 10 -15).…”

Insulin-like Growth Factor 1 (IGF-1) Stabilizes Nascent Blood Vessels

“…Much more is known about the formation of vessels compared with their stabilization and regression (3). Learning how to promote the regression of pathological vessels will potentiate current antiangiogenic approaches that target the formation of neovessels and, thereby, address the unmet needs of patients afflicted by diseases such as cancer or neovascular ocular disorders (4).…”