%0 Journal Article
%A Tisch, Nathalie
%A Freire-Valls, Aida
%A Yerbes, Rosario
%A Paredes, Isidora
%A La Porta, Silvia
%A Wang, Xiaohong
%A Martín-Pérez, Rosa
%A Castro, Laura
%A Wong, Wendy Wei-Lynn
%A Coultas, Leigh
%A Strilic, Boris
%A Gröne, Hermann-Josef
%A Hielscher, Thomas
%A Mogler, Carolin
%A Adams, Ralf H
%A Heiduschka, Peter
%A Claesson-Welsh, Lena
%A Mazzone, Massimiliano
%A López-Rivas, Abelardo
%A Schmidt, Thomas
%A Augustin, Hellmut G
%A Ruiz de Almodovar, Carmen
%T Caspase-8 modulates physiological and pathological angiogenesis during retina development.
%D 2019
%U http://hdl.handle.net/10668/14448
%X During developmental angiogenesis, blood vessels grow and remodel to ultimately build a hierarchical vascular network. Whether, how, cell death signaling molecules contribute to blood vessel formation is still not well understood. Caspase-8 (Casp-8), a key protease in the extrinsic cell death-signaling pathway, regulates cell death via both apoptosis and necroptosis. Here, we show that expression of Casp-8 in endothelial cells (ECs) is required for proper postnatal retina angiogenesis. EC-specific Casp-8-KO pups (Casp-8ECKO) showed reduced retina angiogenesis, as the loss of Casp-8 reduced EC proliferation, sprouting, and migration independently of its cell death function. Instead, the loss of Casp-8 caused hyperactivation of p38 MAPK downstream of receptor-interacting serine/threonine protein kinase 3 (RIPK3) and destabilization of vascular endothelial cadherin (VE-cadherin) at EC junctions. In a mouse model of oxygen-induced retinopathy (OIR) resembling retinopathy of prematurity (ROP), loss of Casp-8 in ECs was beneficial, as pathological neovascularization was reduced in Casp-8ECKO pups. Taking these data together, we show that Casp-8 acts in a cell death-independent manner in ECs to regulate the formation of the retina vasculature and that Casp-8 in ECs is mechanistically involved in the pathophysiology of ROP.
%K Angiogenesis
%K Apoptosis pathways
%K Caspases and caspase substrates
%K Retinopathy
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