title: Pericytes promote selective vessel regression to regulate vascular patterning.
abstract: Blood vessel networks form in a 2-step process of sprouting angiogenesis followed by selective branch regression and stabilization of remaining vessels. Pericytes are known to function in stabilizing blood vessels, but their role in vascular sprouting and selective vessel regression is poorly understood. The endosialin (CD248) receptor is expressed by pericytes associated with newly forming but not stable quiescent vessels. In the present study, we used the Endosialin(-/-) mouse as a means to uncover novel roles for pericytes during the process of vascular network formation. We demonstrate in a postnatal retina model that Endosialin(-/-) mice have normal vascular sprouting but are defective in selective vessel regression, leading to increased vessel density. Examination of the Endosialin(-/-) mouse tumor vasculature revealed an equivalent phenotype, indicating that pericytes perform a hitherto unidentified function to promote vessel destabilization and regression in vivo in both physiologic and pathologic angiogenesis. Mechanistically, Endosialin(-/-) mice have no defect in pericyte recruitment. Rather, endosialin binding to an endothelial associated, but not a pericyte associated, basement membrane component induces endothelial cell apoptosis and detachment. The results of the present study advance our understanding of pericyte biology and pericyte/endothelial cell cooperation during vascular patterning and have implications for the design of both pro- and antiangiogenic therapies.
authors: Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Rd., London, UK.
authors: Nicole
authors: N
authors: Simonavicius
authors: Matthew
authors: M
authors: Ashenden
authors: Antoinette
authors: A
authors: van Weverwijk
authors: Siân
authors: S
authors: Lax
authors: David L
authors: DL
authors: Huso
authors: Christopher D
authors: CD
authors: Buckley
authors: Ivo J
authors: IJ
authors: Huijbers
authors: Ivo J
authors: IJ
authors: Huijber
authors: Helen
authors: H
authors: Yarwood
authors: Clare M
authors: CM
authors: Isacke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D001011:Aorta / Q000254:growth & development / Q000473:pathology; D017209:Apoptosis; D001485:Basement Membrane / Q000378:metabolism; D001808:Blood Vessels / Q000254:growth & development* / Q000473:pathology*; D019521:Body Patterning; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000172:deficiency / Q000378:metabolism; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000254:growth & development; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; C509258:tumor endothelial marker 1, mouse