Role of receptor-mediated endocytosis in the antiangiogenic effects of human T lymphoblastic cell-derived microparticles

• DOI: 10.1152/ajpregu.00527.2011
• Publication Date: 2012-02-16T07:53:25Z
• Authors: Chun Yang; Wei Xiong; Qian Qiu; Zuo Shao; David Hamel; Houda Tahiri; Grégoire Leclair; Pierre Lachapelle; Sylvain Chemtob; Pierre Hardy
• Keywords: 0301 basic medicine; T-Lymphocytes; Endothelial Cells; Retinal Vessels; Retinal Neovascularization; Endocytosis; Cell Line; Rats; 3. Good health; 03 medical and health sciences; Cell Movement; Cell-Derived Microparticles; Animals; Humans; Endothelium, Vascular; Cell Proliferation

Microparticles possess therapeutic potential regarding angiogenesis. We have demonstrated the contribution of apoptotic human CEM T lymphocyte-derived microparticles (LMPs) as inhibitors angiogenic responses in animal models inflammation and tumor growth. In present study, we characterized antivascular endothelial growth factor (VEGF) effects LMPs on pathological angiogenesis an model oxygen-induced retinopathy explored role receptor-mediated endocytosis retinal cells (HRECs). dramatically inhibited cell HRECs, suppressed VEGF-induced migration vitro experiments, attenuated vascular leakage vivo. Intravitreal injections fluorescently labeled revealed accumulation tissue, with more than 60% reductions density retinas rats neovascularization. LMP uptake experiments that interaction between HRECs is dependent temperature. addition, partially extracellular calcium. RNAi-mediated knockdown low-density lipoprotein receptor (LDLR) reduced inhibitory VEGF-A protein expression injection lentivirus-mediated RNA interference LDLR retina by 53% significantly blocked antiangiogenic vascularization. summary, potent lead to a significant reduction through modulation VEGF signaling, whereas LDLR-mediated plays partial, but pivotal, HRECs.