Formation of the Collateral Circulation Is Regulated by Vascular Endothelial Growth Factor-A and A Disintegrin and Metalloprotease Family Members 10 and 17

• DOI: 10.1161/circresaha.112.279109
• Publication Date: 2012-09-11T06:12:02Z
• Authors: Jennifer L. Lucitti; Jessica K. Mackey; Jeffrey C. Morrison; Jody J. Haigh; Ralf H. Adams; James E. Faber
• Keywords: Collateral circulation; Vasculogenesis; Arteriogenesis; Sprouting angiogenesis; Mural cell

Rationale: The density of native (preexisting) collaterals varies widely and is a significant determinant variation in severity stroke, myocardial infarction, peripheral artery disease. However, little known about mechanisms responsible for formation the collateral circulation healthy tissues. Objective: We previously found that vascular endothelial growth factor (VEGF) expression causes differences newborn adult mice. Herein, we sought to determine collaterogenesis embryo role VEGF this process. Methods Results: Pial begin forming between embryonic day 13.5 14.5 as sprout-like extensions from arterioles existing cerebral trees. Global VEGF-A overexpressing mice ( Vegf hi/+ ) formed more, lo/+ fewer, during embryogenesis, association with patterning. Conditional global reduction or Flk1 only significantly reduced formation, but now without affecting patterning, effects remained adulthood. Endothelial-specific had no effect on collaterogenesis. disintegrin-and-metalloprotease-domain-10 Adam10 inhibition γ-secretase increased consistent their roles VEGF-induced Notch1 activation suppression prosprouting signals. knockdown Adam17 its cell migration stabilization, not ligand-bound Notch1. These also Conclusions: Formation pial occurs narrow developmental window via sprouting angiogenesis-like mechanism, requires paracrine stimulation fetal liver kinase 1-Notch signaling, number dependent