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Sự ức chế sự hình thành mạch máu choroid bằng cách chặn kinase tyrosine của thụ thể yếu tố tăng trưởng nội mô mạch máu
Tóm tắt
Nghiên cứu vai trò của các thụ thể yếu tố tăng trưởng nội mô mạch máu, Flt-1 và KDR/Flk-1, trên mô hình thí nghiệm của sự hình thành mạch máu mới choroid (CNV). Inhibitor kinase tyrosine đặc hiệu thụ thể yếu tố tăng trưởng nội mô mạch máu-A (VEGF-A) SU5416 được sử dụng trên mô hình chuột CNV do laser gây ra. Sự hình thành của CNV và mức độ thẩm thấu mạch máu ở chuột thiếu hụt miền kinase tyrosine của Flt-1 cũng được khảo sát. SU5416 đã làm giảm tính mạch và sự tăng sinh tế bào nội mô mạch máu, đồng thời thúc đẩy quá trình apoptosis của tế bào nội mô trong CNV. Hơn nữa, sự hình thành CNV và mức độ thẩm thấu mạch máu đã giảm đáng kể ở chuột thiếu hụt miền kinase tyrosine của Flt-1, và hiệu ứng này được củng cố bởi việc sử dụng SU5416. Cả Flt-1 và KDR/Flk-1 đều có vai trò quan trọng trong sự hình thành CNV. Việc ức chế apoptosis có thể liên quan đến quá trình này.
Từ khóa
#Flt-1 #KDR/Flk-1 #sự hình thành mạch máu mới #yếu tố tăng trưởng nội mô mạch máu #SU5416 #apoptosisTài liệu tham khảo
Leibowitz HM, Krueger DE, Maunder LR, et al. The Framingham Eye Study monograph: an ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973–1975. Surv Ophthalmol 1980;24:335–610.
Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996;380:435–439.
Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1:27–31.
Kvanta A. Expression and regulation of vascular endothelial growth factor in choroidal fibroblasts. Curr Eye Res 1995;14:1015–1020.
Amin R, Puklin JE, Frank RN. Growth factor localization in choroidal neovascular membranes of age-related macular degeneration. Invest Ophthalmol Vis Sci 1994;35:3178–3188.
Yi X, Ogata N, Komada M, et al. Vascular endothelial growth factor expression in choroidal neovascularization in rats. Graefes Arch Clin Exp Ophthalmol 1997;235:313–319.
Wada M, Ogata N, Otsuji T, Uyama M. Expression of vascular endothelial growth factor and its receptor (KDR/flk-1) mRNA in experimental choroidal neovascularization. Curr Eye Res 1999;18:203–213.
Iwashita K, Takahashi K, Wada M, Uyama M. Vascular endothelial growth factor promotes experimental choroidal neovascularization in monkey eyes (in Japanese with English abstract). Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 1999;103:415–424.
Kwak N, Okamoto N, Wood JM, Campochiaro PA. VEGF is major stimulator in model of choroidal neovascularization. Invest Ophthalmol Vis Sci 2000;41:3158–3164.
Cui JZ, Kimura H, Spee C, et al. Natural history of choroidal neovascularization induced by vascular endothelial growth factor in the primate. Graefes Arch Clin Exp Ophthalmol 2000;238:326–333.
Gerber HP, McMurtrey A, Kowalski J, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 1998;273:30336–30343.
Gerber HP, Dixit V, Ferrara N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem 1998;273:13313–13316.
Alon T, Hemo I, Itin A, et al. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1995;1:1024–1028.
Shibuya M, Ito N, Claesson-Welsh L. Structure and function of VEGF Receptor-1 and-2. Curr Topics Microbiol Immunol 1999;237:59–83.
Seetharam L, Gotoh N, Maru Y, et al. A unique signal transduction from FLT tyrosine kinase, a receptor for vascular endothelial growth factor VEGF. Oncogene 1995;10:135–147.
Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M, Heldin CH. Different signal transduction properties of KDR and Flt-1, two receptors for vascular endothelial growth factor. J Biol Chem 1994;269:26988–26995.
Takahashi T, Yamaguchi S, Chida K, Shibuya M. A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO J 2001;20:2768–2778.
Luttun A, Tjwa M, Moons L, et al. Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 2002;8:831–840.
Hiratsuka S, Minowa O, Kuno J, Noda T, Shibuya M. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci U S A 1998;95:9349–9354.
Hiratsuka S, Maru Y, Okada A, et al. Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis. Cancer Res 2001;61:1207–1213.
Itokawa T, Nokihara H, Nishioka Y, et al. Antiangiogenic effect by SU5416 is partly attributable to inhibition of Flt-1 receptor signaling. Mol Cancer Ther 2002;1:295–302.
Takeda A, Hata Y, Shiose S, et al. Suppression of experimental choroidal neovascularization utilizing KDR selective receptor tyrosine kinase inhibitor. Graefes Arch Clin Exp Ophthalmol 2003;241:765–772.
Dobi ET, Puliafito CA, Destro M. A new model of experimental choroidal neovascularization in the rat. Arch Ophthalmol 1989;107:264–269.
Yanagi Y, Tamaki Y, Obata R, et al. Subconjunctival administration of bucillamine suppresses choroidal neovascularization in rat. Invest Ophthalmol Vis Sci 2002;43:3495–3499.
Takehana Y, Kurokawa T, Kitamura T, et al. Suppression of laser-induced choroidal neovascularization by oral tranilast in the rat. Invest Ophthalmol Vis Sci 1999;40:459–466.
Yanagi Y, Tamaki Y, Inoue Y, et al. Subconjunctival doxifluridine administration suppresses rat choroidal neovascularization through activated thymidine phosphorylase. Invest Ophthalmol Vis Sci 2003;44:751–754.
Adamis AP, Shima DT, Tolentino MJ, et al. Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Arch Ophthalmol 1996;114:66–71.
Fong TA, Shawver LK, Sun L, et al. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res 1999;59:99–106.
Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983;219:983–985.
Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995;146:1029–1039.
Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev 1997;18:4–25.
Gupta K, Ramakrishnan S, Browne PV, Solovey A, Hebbel RP. A novel technique for culture of human dermal microvascular endothelial cells under either serum-free or serum-supplemented conditions: isolation by panning and stimulation with vascular endothelial growth factor. Exp Cell Res 1997;230:244–251.
Aiello LP, Pierce EA, Foley ED, et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A 1995;92:10457–10461.
Seo MS, Kwak N, Ozaki H, et al. Dramatic inhibition of retinal and choroidal neovascularization by oral administration of a kinase inhibitor. Am J Pathol 1999;154:1743–1753.
Krzystolik MG, Afshari MA, Adamis AP, et al. Prevention of experimental choroidal neovascularization with intravitreal antivascular endothelial growth factor antibody fragment. Arch Ophthalmol 2002;120:338–346.
Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480–1487.
Adamis AP, Miller JW, Bernal MT, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 1994;118:445–450.
Aiello LP, Northrup JM, Keyt BA, Takagi H, Iwamoto MA. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol 1995;113:1538–1544.
Nozaki M, Sakurai E, Raisler BJ, et al. Loss of SPARC-mediated VEGFR-1 suppression after injury reveals a novel antiangiogenic activity of VEGF-A. J Clin Invest 2006;116:422–429.
Rakic JM, Lambert V, Devy L, et al. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest Ophthalmol Vis Sci 2003;44:3186–3193.
Carmeliet P, Moons L, Luttun A, et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 2001;7:575–583.
Shen J, Samul R, Silva RL, et al. Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1. Gene Ther 2006;13:225–234.
Takehana Y, Kurokawa T, Kitamura T, et al. Suppression of laser-induced choroidal neovascularization by oral tranilast in the rat. Invest Ophthalmol Vis Sci 1999;40:459–466.
