Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
Cells. 2020 Jan 23;9(2):280. doi: 10.3390/cells9020280.
Bone morphogenetic protein-7 is (BMP-7) is a potent anti-inflammatory growth factor belonging to the Transforming Growth Factor Beta (TGF-β) superfamily. It plays an important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis. BMP-7 stimulates the target cells by binding to specific membrane-bound receptor BMPR 2 and transduces signals through mothers against decapentaplegic (Smads) and mitogen activated protein kinase (MAPK) pathways. To date, rhBMP-7 has been used clinically to induce the differentiation of mesenchymal stem cells bordering the bone fracture site into chondrocytes, osteoclasts, the formation of new bone via calcium deposition and to stimulate the repair of bone fracture. However, its use in cardiovascular diseases, such as atherosclerosis, myocardial infarction, and diabetic cardiomyopathy is currently being explored. More importantly, these cardiovascular diseases are associated with inflammation and infiltrated monocytes where BMP-7 has been demonstrated to be a key player in the differentiation of pro-inflammatory monocytes, or M1 macrophages, into anti-inflammatory M2 macrophages, which reduces developed cardiac dysfunction. Therefore, this review focuses on the molecular mechanisms of BMP-7 treatment in cardiovascular disease and its role as an anti-fibrotic, anti-apoptotic and anti-inflammatory growth factor, which emphasizes its potential therapeutic significance in heart diseases.
骨形态发生蛋白 7(BMP-7)是一种有效的抗炎生长因子,属于转化生长因子β(TGF-β)超家族。它在各种生物学过程中发挥着重要作用,包括胚胎发生、造血、神经发生和骨骼形态发生。BMP-7 通过与特定的膜结合受体 BMPR2 结合来刺激靶细胞,并通过母体对抗 decapentaplegic(Smads)和丝裂原激活蛋白激酶(MAPK)途径传递信号。迄今为止,rhBMP-7 已在临床上用于诱导骨折部位边缘的间充质干细胞分化为软骨细胞、破骨细胞、通过钙沉积形成新骨,并刺激骨折修复。然而,它在心血管疾病中的应用,如动脉粥样硬化、心肌梗死和糖尿病性心肌病,目前正在探索中。更重要的是,这些心血管疾病与炎症和浸润的单核细胞有关,其中 BMP-7 已被证明是将促炎单核细胞或 M1 巨噬细胞分化为抗炎 M2 巨噬细胞的关键因子,从而减少已发生的心脏功能障碍。因此,本综述重点介绍了 BMP-7 在心血管疾病中的治疗分子机制及其作为抗纤维化、抗细胞凋亡和抗炎生长因子的作用,强调了其在心脏病治疗中的潜在治疗意义。