肾胺酶(Renalase, Rnls)是最初发现在肾脏表达的胺氧化酶，通过代谢儿茶酚胺调节血压；近期研究（包括我们）发现Rnls在心脏高表达，与心肌缺血、心室重构及心衰等心功能异常密切相关。而左室肥厚（LVH）是心功能异常的早期代偿性改变，多种因素可激活mTORC1（雷帕霉素靶蛋白）这一细胞生长核心调控分子促进LVH。我们近期预实验发现：高血压伴LVH患者血浆Rnls浓度较无LVH患者显著升高；大鼠LVH模型中，心肌Rnls表达显著上调，且与肥厚程度呈正相关；体外心肌肥大模型中，干扰Rnls基因能抑制细胞肥大，同时磷酸化mTORC1表达下调，但肾胺酶与mTORC1鲜有报道。故本课题率先提出：Rnls调控mTORC1促进LVH。我们拟采用Rnls-/-小鼠及心肌局部Rnls干扰模型，研究Rnls在LVH中的作用及分子机制。这一机制的阐明有望为Rnls作为干预LVH的新靶点奠定重要理论依据。

Renalase (Rnls), a novel flavoprotein mainly expressed in the kidney, has been known to degrade circulating catecholamines and play a crucial role in hypertension via its ability of amine oxidase. Subsequent studies (including our researches) have found that renalase is highly expressed in heart and plays an important role in many pathological injury processes, such as, myocardial ischemia injury, ventricular remodeling, and heart failure and so on. Those functions of renalase is independent on its enzyme ability. As we known, left ventricular hypertrophy, one kind of compensatory structural change in heart, is an early period change of cardiac dysfunction. Many factors (including pressure overload, inflammatory activation, and oxidation stress and so on) directly or indirectly activates mTORC1 (rapamycin target protein complex1) signaling to promote left ventricular hypertrophy. However, whether renalase regulates ventricular hypertrophy and whether renalase activates mTORC1 signaling is unclear. What’s interesting, our recent data had found that there were higher plasma level of renalase in patients with left ventricular hypertrophy (LVH) than those without LVH. Moreover, in the local hearts of spontaneously hypertensive rats, we found that renalase increasingly expressed along with the development of spontaneously ventricular hypertrophy. To further investigate the relationship between renalase and ventricular hypertrophy, we established a modal of pressure overload induced left ventricular hypertrophy with adult SD rats. It’s a significant founding that renalase expression gradually increased along with the progress of left ventricular hypertrophy. In addition, we got the same result in myocardium hypertrophic modal in vitro, inhibition of renalase gene obviously reduced the progress of cell hypertrophy which noradrenaline induced, and phosphorylation of mTORC1 is significantly down-regulated, however, the relationship between renalase and mTORC1 is also unknown. Therefore, we propose that renalse promotes the left ventricular hypertrophy by regulating mTORC1 signaling. We use Rnls-/- mouse modal and lentivirus mediated Rnls gene interference modal to study its role in left ventricular hypertrophy, and systematically eluminate the molecular mechanism of renalase regulates mTORC1 signaling. Finally, renalase is expected to be a potential and novel target for inhibiting left ventricular hypertrophy.