心室重构是心力衰竭患者心功能从代偿转向失代偿的关键事件，现有药物和治疗手段效果不佳。甘氨酸是一种人体非必须氨基酸，在生长、发育、代谢和神经传递等多个生命过程中发挥重要作用。我们的前期研究提示甘氨酸能够拮抗细胞ATP耗竭时的损伤反应，这一作用依赖于甘氨酸受体的介导；甘氨酸在心脑缺血性损伤反应中发挥重要的保护作用。基于上述研究成果，我们提出假说，甘氨酸可能具有拮抗心肌肥大和心肌纤维化所引起的心室重构的作用，因而可用于阻止心衰的发展。我们的预实验结果提示，甘氨酸减轻压力负荷诱导的小鼠心肌肥大和纤维化；在体外抑制心肌细胞ERK1/2磷酸化。有趣的是，甘氨酸不能直接抑制心脏成纤维细胞胶原合成，而甘氨酸受体只在心肌细胞上表达，不在成纤维肌细胞上表达。甘氨酸是否通过旁分泌机制影响心脏纤维化？为此，本项目拟从在体和离体两个方面开展试验，深入研究甘氨酸在调控心室重构中的作用及其机制，为临床治疗提供新的思路。

Cardiac remodeling is a precursor of clinical heart failure which pump function turns maladaptation. Despite advances in diagnosis and treatments during past decades, the survival rate after the onset of cardiac remodeling still remains very low. As a non-essential amino acid, glycine has multiple functions in metabolism, growth, development, and cytoprotection. In the previous studies, we found that glycine increased activity in the cells in which glycine receptor (GlyR) was expressed under conditions of ATP depletion, and played an important role in cardio-cerebral ischemic injury. Based on these, we propose glycine may antagonize pathological cardiac remodeling, which can be used to prevent the development of heart failure. Our preliminary experiments indicate that glycine attenuates pressure overload caused cardiac hypertrophy and fibrosis in vivo. Glycine reduces the hypertrophic cardiomyocyte response to Ang II, and inhibits phosphorylation of ERK1/2 in vitro. Interestingly, glycine failed in inhibiting the increased collagen production induced by Ang II, and GlyR is only found at cardiomyocyte. We hypothesize glycine may reduce cardiac fibrosis by regulating paracrine mechanism. To test this hypothesis, our proposal intends to explore the protective effect of glycine on myocardial remodeling and its potential mechanism from in vivo and in vitro. This study will be helpful to provide new therapeutic targets for cardiac remodeling.