Bone Morphogenetic Protein 2  (骨形态发生蛋白 2)

骨形态发生蛋白 2 (BMP-2) 是一种多效性配体蛋白，属于 TNFβ 家族。BMP-2 形成 BMP/TGFβ 信号，参与血管和瓣膜稳态，这是胚胎发育的关键过程^[1]。BMP-2/TGFβ 信号可以被抑制性 SMADs 终止，包括 SMAD6 和 SMAD7，SMAD6 被 BMP 信号激活和诱导，并通过多种机制关闭 BMP 信号^[2]。BMP-2 广泛存在于不同的动物中，而人类的序列与大鼠（91.86%）和小鼠（92.13%）相似。BMPs 对动脉粥样硬化、肺血管疾病以及血管和瓣膜钙化的病理生理学有重要贡献^[1]。BMP-2 结合不同的受体，如 I 型受体 (ALK-2/-3/-6) 和 II 型受体 (BMPR2, ACVR2A)，以调节各种钙化类型^[1]。BMP-2 促进动脉粥样硬化军团的单核细胞浸润和炎症^[3]。它通过促炎和促动脉粥样硬化作用、促进氧化应激、内皮功能障碍，并和成骨分化与斑块形成增加有关^[4]。BMP-2 在人钙化瓣膜的骨化区域中由 B 淋巴细胞和 T 淋巴细胞密集浸润区域的肌成纤维细胞和前成骨细胞过度表达^[5]，是动脉粥样硬化血管钙化与正常骨形成机制之间的连接点^[6]。BMP-2 诱导血管生成、内皮细胞 (EC) 增殖和迁移^[7]。BMP-2 还增强成骨细胞和软骨细胞主转录调节因子 RUNX2 的表达，以促进培养的人冠状动脉平滑肌细胞的矿化，其方式依赖于氧化应激和内质网 (ER) 应激^[8]。

Bone Morphogenetic Protein 2 (BMP-2) is a ligand protein with pleiotropic, belongs to TNFβ family. BMP-2 formats BMP/TGFβ signaling to involve in vascular and valvular homeostasis, which is a critical process of embryonic development^[1]. BMP-2/TGFβ signaling can be terminated by inhibitory SMADs including SMAD6 and SMAD7, which are activated and induced by BMP signaling and switch off BMP signaling via multiple mechanisms^[2]. BMP-2 is widely found in different animals, while the sequence in human is similar to Rat (91.86%), and mouse (92.13%). BMPs exhibits critical contributions to the pathophysiology of atherosclerosis, pulmonary vascular disease, and vascular and valvular calcification^[1]. BMP-2 binds different receptor, such as type I receptors (ALK-2/-3/-6) and type II receptors (BMPR2, ACVR2A), to regulate various calcification type^[1]. BMP-2 promotes monocyte infiltration and inflammation of atherosclerotic legions^[3]. It is linked to increased plaque formation via pro-inflammatory and pro-atherogenic effects, promoting oxidative stress, endothelial dysfunction and osteogenic differentiation^[4]. BMP-2 is overexpressed in ossified regions of human calcified valves by myofibroblasts and pre-osteoblasts in areas densely infiltrated with B- and T-lymphocytes^[5]. And it serves as the linkers between atherosclerotic vascular calcification with mechanisms of normal bone formation^[6]. BMP-2 induces angiogenesis, endothelial cells (ECs) proliferation, and migration^[7]. And BMP-2 also enhances the expression of the osteoblast and chondrocyte master transcriptional regulator RUNX2 to promote the mineralization of cultured human coronary vascular SMCs in a manner that was dependent on oxidative stress and endoplasmic reticulum (ER) stress^[8].

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