Endogenous endostatin inhibits choroidal neovascularization
Endogenous endostatin inhibits choroidal neovascularization
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DOI：
10.1096/fj.07-8422com
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发表时间：
2007-12-01
期刊：
影响因子：
4.8
通讯作者：
Olsen, Bjorn R.
中科院分区：
文献类型：
--
作者：
Marneros, Alexander G.;She, Haicheng;Olsen, Bjorn R.
内皮抑制素是基底膜组分胶原XVIII的片段，当给予高剂量时，在体外和体内表现出抗血管生成特性。目前尚不清楚生理水平的内源性内皮抑制素是否具有作为病理性血管生成（如年龄相关性黄斑变性中的脉络膜新生血管形成（CNV））的抑制剂的保护作用。使用激光损伤模型，我们在缺乏胶原蛋白XVIII/内皮抑素的小鼠和对照小鼠中诱导CNV。突变小鼠的CNV病变比对照小鼠大3倍，并显示血管渗漏增加。这些差异与年龄相关的脉络膜-视网膜界面变化无关。突变小鼠脉络膜血管的超微结构分析排除了血管形态异常作为较大CNV病变的原因。当将重组内皮抑制素给予胶原蛋白XVIII/内皮抑制素缺陷小鼠时，CNV损伤与对照小鼠中观察到的那些相似。在用重组内皮抑素治疗的对照小鼠中，CNV病变几乎检测不到。这些发现表明内源性内皮抑制素是诱导的血管生成的抑制剂，并且施用内皮抑制素有效地抑制CNV生长和血管渗漏。内皮抑素可能在CNV的发病机制中起调节作用，并可用于治疗CNV病变的生长和渗漏。
Endostatin, a fragment of the basement membrane component collagen XVIII, exhibits antiangiogenic properties in vitro and in vivo when high doses are administered. It is not known whether endogenous endostatin at physiological levels has a protective role as an inhibitor of pathological angiogenesis, such as choroidal neovascularization ( CNV) in age- related macular degeneration. Using a laser injury model, we induced CNV in mice lacking collagen XVIII/ endostatin and in control mice. CNV lesions in mutant mice were similar to 3-fold larger than in control mice and showed increased vascular leakage. These differences were independent of age- related changes at the choroid-retina interface. Ultrastructural analysis of the choroidal vasculature in mutant mice excluded morphological vascular abnormalities as a cause for the larger CNV lesions. When recombinant endostatin was administered to collagen XVIII/ endostatin- deficient mice, CNV lesions were similar to those seen in control mice. In control mice treated with recombinant endostatin, CNV lesions were almost undetectable. These findings demonstrate that endogenous endostatin is an inhibitor of induced angiogenesis and that administration of endostatin potently inhibits CNV growth and vascular leakage. Endostatin may have a regulatory role in the pathogenesis of CNV and could be used therapeutically to inhibit growth and leakage of CNV lesions.