Apoptotic cells initiate endothelial cell sprouting via electrostatic signaling.
Angiogenesis, the development of new blood vessels from preexisting vessels, is crucial to tissue growth, repair, and maintenance. This process begins with the formation of endothelial cell sprouts followed by the proliferation and migration of neighboring endothelial cells along the preformed extensions. The initiating event and mechanism of sprouting is not known. We show that the phenotypic expression of negatively charged membrane surface in apoptotic cells initiates the formation of directional endothelial cell sprouts that extend toward the dying cells by a mechanism that involves endothelial cell membrane hyperpolarization and cytoskeleton reorganization but is independent of diffusible molecules.
Weihua
Zhang
Z
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, 77230, USA.
Tsan
Rachel
R
Schroit
Alan J
AJ
Fidler
Isaiah J
IJ
D000818:Animals; D017209:Apoptosis; D002450:Cell Communication; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005293:Ferritins / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D051381:Rats; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012685:Sepharose / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D055672:Static Electricity
D007473:Ion Channels; D010743:Phospholipids; D011687:Purines; D016222:Fibroblast Growth Factor 2; D005293:Ferritins; D012685:Sepharose; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor; C489254:AEE 788