miR-542-3p调控BMP7通路在老龄VSMC向成骨样表型转化中作用及机制研究

血管钙化随年龄增加逐渐加重，但增龄促血管钙化的机制尚不完全清楚。目前认为VSMC向成骨样表型转化是血管钙化的关键环节。我们研究发现miR-542-3p在老龄VSMC中显著下调，致VSMC收缩表型丧失，同时促进VSMC向成骨样表型转化，但机制不清。生物信息学预测BMP7是miR-542-3p潜在靶基因，VSMC中miR-542-3p表达水平与BMP7负相关。既往研究提示BMP7可能通过下游效应分子Jagged1和/或Runx2促VSMC向成骨样表型转化。因而提出假说：老龄VSMC中miR-542-3p减少，导致BMP7表达上调，从而促VSMC向成骨样表型转化。本项目拟利用VSMC诱导钙化模型和老龄ApoE-/-小鼠血管钙化模型，阐明miR-542-3p调控BMP7通路在老龄VSMC向成骨样表型转化中作用及机制。通过本项目有望完善老龄促血管钙化的分子机制，为临床防治老年人血管钙化提供新的思路。

The vascular calcification was severe along with the age increase gradually, but the mechanism is not completely clear.The osteoblast-like phenotypic transformation of vascular smooth muscle cells(VSMC) was thought to be the key link of vascular calcification. We have found that the expression of miR-542-3p was significantly down regulated in VSMC by aging, which lead to lose the function of contractile phenotype of VSMC, and at the same time to accelerate osteoblast-like phenotypic transformation of VSMC, but the mechanism is not clear. Bioinformatics predicted that the BMP7 is potential target genes of miR-542-3p, which showed a negative correlation of the expression level of miR-542-3p and BMP7 in VSMC. Previous studies suggested that the BMP7 may accelerate the osteoblast-like phenotypic transformation of VSMC by downstream effectors Jagged1 and/or Runx2.Thus the hypothesis was put forward that the lower expression of miR-542-3p in aging VSMC, could induce up-regulation expression of BMP7, and then promote the osteoblast-like phenotypic transformation of VSMC. This project intends to clarify the effect and mechanism of BMP7 regulated by miR-542-3p on osteoblast-like phenotypic transformation of VSMC induced by aging through induced VSMC calcification model and aging ApoE-/- mice model of vascular calcification, expect to perfect the molecular mechanisms of vascular calcification by aging, and provide a new thinking for clinical prevention and treatment of vascular calcification in the elderly.