Newly Identified Peptide, Peptide Lv, Promotes Pathological Angiogenesis.
Newly Identified Peptide, Peptide Lv, Promotes Pathological Angiogenesis.
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新鉴定的肽 Lv 可促进病理性血管生成。
DOI：
10.1161/jaha.119.013673
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发表时间：
2019
影响因子：
5.4
通讯作者：
Ko,GladysY-P
中科院分区：
文献类型：
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作者：
Shi,Liheng;Zhao,Min;Abbey,ColetteA;Tsai,Shu-Huai;Xie,Wankun;Pham,Dylan;Chapman,Samantha;Bayless,KaylaJ;Hein,TravisW;RosaJr,RobertH;Ko,MichaelL;Kuo,Lih;Ko,GladysY-P
背景我们最近发现了一种内源性小肽Lv，它具有激活血管内皮生长因子受体2及其下游信号传导的能力。由于血管内皮生长因子通过血管内皮生长因子受体2参与正常发育、血管舒张、血管生成以及各种疾病的发病机制，因此我们在本研究中研究了肽Lv在血管舒张以及发育和病理性血管生成中的作用。三维发芽实验检测Lv肽体外促血管生成能力。采用鸡胚绒毛尿囊膜和出生后早期小鼠研究其对发育性血管生成的影响。氧诱导的视网膜病变和激光诱导的脉络膜新生血管形成小鼠模型用于体内病理性血管生成。分离的猪视网膜和冠状小动脉用于血管舒张测定。在体外和体内，肽Lv引起血管生成。Lv肽和血管内皮生长因子协同促进内皮细胞增殖。Lv肽引起的血管舒张不完全依赖于一氧化氮，表明Lv肽具有血管内皮生长因子受体2/一氧化氮非依赖性靶点。抗Lv肽的抗体，抗Lv，抑制血管内皮生长因子引起的内皮细胞增殖和激光诱导的血管渗漏和脉络膜新生血管形成。虽然外源性肽Lv增强了氧诱导视网膜病变小鼠眼睛中的病理性血管生成，但抗Lv抑制了这一过程。此外，删除肽Lv在小鼠中显着降低病理性新生血管形成相比，其野生型littermates.ConclusionsThese结果表明，肽Lv在病理性血管生成中起着重要作用，但在发展过程中可能不那么重要。Lv肽通过血管内皮生长因子受体2依赖性和非依赖性途径参与病理性血管生成.由于抗Lv抑制了眼部的病理性血管生成，因此抗Lv可能具有治疗病理性血管生成的治疗潜力。
BackgroundWe recently discovered a small endogenous peptide, peptide Lv, with the ability to activate vascular endothelial growth factor receptor 2 and its downstream signaling. As vascular endothelial growth factor through vascular endothelial growth factor receptor 2 contributes to normal development, vasodilation, angiogenesis, and pathogenesis of various diseases, we investigated the role of peptide Lv in vasodilation and developmental and pathological angiogenesis in this study.Methods and ResultsThe endothelial cell proliferation, migration, and 3‐dimensional sprouting assays were used to test the abilities of peptide Lv in angiogenesis in vitro. The chick chorioallantoic membranes and early postnatal mice were used to examine its impact on developmental angiogenesis. The oxygen‐induced retinopathy and laser‐induced choroidal neovascularization mouse models were used for in vivo pathological angiogenesis. The isolated porcine retinal and coronary arterioles were used for vasodilation assays. Peptide Lv elicited angiogenesis in vitro and in vivo. Peptide Lv and vascular endothelial growth factor acted synergistically in promoting endothelial cell proliferation. Peptide Lv–elicited vasodilation was not completely dependent on nitric oxide, indicating that peptide Lv had vascular endothelial growth factor receptor 2/nitric oxide–independent targets. An antibody against peptide Lv, anti‐Lv, dampened vascular endothelial growth factor–elicited endothelial proliferation and laser‐induced vascular leakage and choroidal neovascularization. While the pathological angiogenesis in mouse eyes with oxygen‐induced retinopathy was enhanced by exogenous peptide Lv, anti‐Lv dampened this process. Furthermore, deletion of peptide Lv in mice significantly decreased pathological neovascularization compared with their wild‐type littermates.ConclusionsThese results demonstrate that peptide Lv plays a significant role in pathological angiogenesis but may be less critical during development. Peptide Lv is involved in pathological angiogenesis through vascular endothelial growth factor receptor 2–dependent and –independent pathways. As anti‐Lv dampened the pathological angiogenesis in the eye, anti‐Lv may have a therapeutic potential to treat pathological angiogenesis.