线粒体分裂蛋白DRP1诱导血管平滑肌细胞表型转化参与主动脉夹层的作用机制研究

主动脉夹层是最危险的心血管病急症，严重影响患者健康，给患者个人、家庭和社会带来沉重负担。在主动脉夹层发生过程中，中层退化扮演着重要的角色，但在高血压诱发主动脉夹层的病理过程中，关于线粒体形态改变以及血管平滑肌细胞表型改变之间的联系仍不明确。我们前期研究发现在常年高血压诱发夹层的患者组织中，VSMC呈分泌型改变，线粒体肿胀、碎片化。组织水平检测发现疾病组DRP1高表达，同时伴随有线粒体功能障碍，因此我们推测高血压夹层患者VSMC中，DRP1表达升高，细胞线粒体裂变增多，促使VSMC表型改变，加速中层退化；这可能是高血压诱发主动脉夹层的分子机制之一。本课题将从在体、细胞与分子水平，研究①DRP1对于线粒体动态平衡的调节影响VSMC表型改变的联系；②高血压状态下VSMC表型改变与线粒体能量代谢的关系；③Ca2+-钙调磷酸酶调节DRP1调控主动脉中层退化的具体机制。

Aortic dissection (AoD) is the most dangerous cardiovascular emergency, which bring a heavy burden to the social and family because of its poor prognosis. Medium degeneration plays important role during the pathogenesis of AoD. However, it is still uncertain about the relation between mitochondria dynamics and VSMC transversion in disease aorta. Recently our study reveals high percentage of secretory VSMC accumulated in the medium accompanied with mitochondria fragmentation. What’s more, we also find the increasing expression of DRP1 in AoD patients. These evidences strongly suggest that increasing level of DRP1 induce the mitochondria fission, which will participate in VSMC transversion, finally accelerate medium degeneration. In the meantime, we will focus on the biological function of DRP1 in the pathogenesis of AoD. Above all, this study will provide theoretical basis of finding new targets for the prevention of AoD.