血管平滑肌细胞去分化，增殖和迁移是发生以血管新生内膜形成为基本病理改变的增生血管疾病的细胞学基础。我们最近的研究发现， 线粒体能产生较细胞核含量更高的10几种lncRNAs。 其中一种线粒体lncRNA与细胞ATP的产生有关。我们将其命名为EnermtRNA-1。 我们发现可以进入到细胞核和细胞质中，其在血清或PDGF诱导的VSMCs，小鼠损伤后增生的血管壁以及人类增生的血管壁中表达含量显著升高。但其在血管生物学及血管疾病的中的作用在国际上尚未见报道。本研究将在分子，细胞及动物水平，结合人的疾病标本，来探索EnermtRNA-1在VSMCs功能及血管新生内膜形成的作用及其分子机制。本课题的中心假说是以EnermtRNA-1为中心的新的分子机制及其信号传导途径可能在VSMCs功能改变，VSMCs能量代谢及血管内膜形成中起着重要的作用,可能会成为增生性血管疾病如冠心病，中风等治疗的一个新靶点。

Vascular neointimal growth is the key pathological change of a variety of proliferative vascular diseases, in which dedifferentiation, proliferation, migration of vascular smooth muscle cells (VSMCs) are key cellular events. According to our recent findings, the copy numbers of over ten mitochondrial lncRNAs are much higher than nuclear lncRNAs, including one is related to ATP generation. We named it as EnermtRNA-1. It can exit mitochondria to the cytosol and the nucleus and incredibly up-regulated in proliferative VSMCs stimulated with PDGF or serum, in mouse carotid arteries after ligation injury and human arteries with neointimal growth. However, to date, no studies have been performed to determine its roles in cardiovascular cell biology and in vascular disease. The goal of this proposal is to determine the roles of this novel non-coding mitochondrial RNA, EnermtRNA-1 in VSMC bioenergy, VSMC biology and vascular neointimal formation, and the potential mechanisms involved. Our hypothesis is that EnermtRNA-1 is up-regulated in VSMCs and vascular walls via PI3K/AKT/mtTFA pathway. EnermtRNA-1 is a critical mitochondrial lncRNA in VSMC dedifferentiation, proliferation, migration and apoptosis, and vascular neointimal growth via the enhanced cell bioenergy and the reduced its target signaling pathway: TOE1/p21. Our hypothesis is supported by our preliminary data. EnermtRNA-1 may be a novel therapeutic target for proliferative vascular diseases.