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The Regulation of Bone Morphogenetic Protein Signaling in Endothelial Physiology and Pulmonary Hypertension
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摘要: 骨形态形成蛋白(bone morphogenetic protein, BMP)家族成员除在胚胎发育早期的中胚层形成过程中发挥作用外，其在血管功能紊乱过程中亦发挥重要作用，如参与调控内皮细胞成管、迁移和氧化应激效应等。BMP信号通路的异常与多种心肺血管疾病的发生、发展相关，如肺动脉高压、遗传性出血性毛细血管扩张症和动脉粥样硬化。本文主要阐述BMP信号通路在不同内皮细胞中的功能，以及BMP9和BMP10在肺动脉高压相关病理过程中的调控机制。Abstract: Family members of bone morphogenetic protein(BMP) play an important role in mesoderm formation during embryonic development. They are also involved in angiogenesis, migration, and oxidative stress responses. The abnormal BMP signaling pathway results in a variety of cardiopulmonary vascular diseases, such as pulmonary hypertension, hereditary hemorrhagic telangiectasia, and atherosclerosis. This review focused on the different functions of BMP signaling in several types of endothelial cells, and the differential regulation mechanism by BMP9/10 for the occurrence of pulmonary hypertension.利益冲突： 无
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表 1 BMP在不同类型内皮细胞中的作用及机制
BMP配体 Ⅰ型受体 Ⅱ型受体 内皮细胞类型 生理作用 相关机制 文献 BMP2 ALK3(BMPR1A) BMPRⅡ HUVEC 上调迁移、成管能力 - [11] BMP4 ALK6(BMPR1B) ACTRⅡA 小鼠PVEC 上调增殖能力 上调VEGF [30] ACTRⅡB 小鼠视网膜血管内皮细胞 下调成管能力 下调VEGF和基质金属蛋白酶-9 [16] BMP2/4 BAEC 上调增殖、成管能力 上调VEGF [31] BMP9 ALK1 BMPRⅡ HPAEC 上调成管能力 上调内皮素-1 [18] ALK2 BMPRⅡA EC 上调增殖、成管能力 上调VEGFR/Tie2 [17] ACTRⅡB BAEC
HMEC下调增殖、迁移能力
下调增殖、迁移能力-
-[20-21]
[20-21]BMP9/10 小鼠视网膜血管内皮细胞 下调成管能力 - [26, 28] HUVEC 下调成管能力 上调Notch通路 [28-29] BMP：骨形态形成蛋白; ALK：活化素受体样激酶; BMPR：骨形态形成蛋白受体; ACTR：活化素受体; HUVEC：人脐静脉内皮细胞; PVEC：肺血管内皮细胞; BAEC：牛动脉内皮细胞; HPAEC：人肺动脉内皮细胞; EC：内皮细胞; HMEC：人皮肤微血管内皮细胞; VEGF：血管内皮生长因子; VEGFR：血管内皮生长因子受体; Tie2：酪氨酸蛋白激酶2;-：尚不明确 
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