褪黑素通过血管壁微环境中内皮细胞源性外泌体抑制动脉中膜钙化的旁分泌机制研究

褪黑素在心血管疾病中起着重要的作用，我们今年发表的研究证实褪黑素通过血管平滑肌细胞（VSMCs）的旁分泌作用，抑制动脉中膜钙化，我们前期研究发现褪黑素可以诱导内皮细胞分泌富含miR-7a-5p的外泌体，该外泌体被VSMCs摄取后，抑制VSMCs向成骨样细胞分化。本项目通过在动脉中膜钙化的细胞模型、动物模型和内皮细胞特异性敲除miR-7a-5p和VSMCs特异性敲除PARP1基因工程小鼠，证实在血管壁微环境中，褪黑素通过调控内皮细胞和VSMCs间的crosstalk，探讨褪黑素诱导内皮细胞分泌富含miR-7a-5p的外泌体被VSMCs摄取后，抑制动脉中膜钙化的分子机制。本项目从血管壁微环境出发，解析内皮细胞来源外泌体与VSMCs之间的crosstalk介导褪黑素抑制动脉中膜钙化的作用，为探索褪黑素抑制动脉中膜钙化的病理生理机制开辟崭新的思路。

Melatonin played an important role in cardiovascular diseases. Our recent published results showed melatonin attenuate arterial medial calcification through a VSMCs dependent paracrine manner. Our previous study demonstrated melatonin could induce endothelial cells secreting miR-7a-5p enriched exosomes, and these exosomes could attenuate the osteoblastic differentiation of VSMCs after uptaken by VSMCs. Our present study explore the mechanism involved in melatonin attenuate the arterial medial calcification through the crosstalk between endothelial cells and VSMCs, using cell model and animal model of arterial medial calcification, as well as endothelial cell-specific miR-7a-5p knockout mice and vascular smooth muscle cell-specific PARP1 knockout mice. Based on the arterial wall microenvirment, our present study devotes to bring light on the new mechanism of arterial medial calcification involved in melatonin. The present study will reveal the pathophysiology of melatonin attenuate arterial medial calcification.