冠状动脉微循环功能障碍，严重影响多种心血管疾病的预后。微循环阻塞后的微血管新生是代偿心脏功能的关键之一。既往发现，微血管可感知心肌代谢产物的变化并调节自身功能，但代谢小分子能否影响微血管新生，尚不明确。课题组前期在小鼠冠脉微栓塞模型中发现少量微血管新生，但不足以代偿心功能障碍；心肌代谢组学发现多种代谢小分子改变，其中L-肉碱显著减少；体外应用L-肉碱刺激心肌微血管内皮细胞，显著促进NO释放及VEGF表达，推测L-肉碱可能促进冠脉微血管的新生。本课题拟构建基因敲除肉碱脂酰转移酶（CPT）的小鼠冠脉微栓塞模型，结合心肌PET核素检查，探索L-肉碱对微血管新生和心肌代谢的影响及机制；在心肌微血管内皮细胞水平，明确L-肉碱在微血管内皮细胞生长、成血管反应中的分子机制。同时，在冠脉无复流的临床队列中探索L-肉碱水平对微血管阻塞、临床心血管预后的影响。进而为改善冠脉微血管障碍所致的心肌损伤提供新思路。

Coronary microvascular dysfunction significantly influences the clinical prognosis of several cardiac diseases. Microvascular angiogenesis after microcirculation injury is the key to maintain cardiac function. Previous studies suggested that microvessel underwent self-function alteration via sensing metabolites changes in myocardial microenvironment. However, it was unclear whether metabolites could stimulate microvascular angiogenesis. In our previous work, we confirmed a few of microvascular angiogenesis after coronary microembolization, which could not reverse cardiac dysfunction. We also found myocardial level of L-carnitine was decreased significantly in metabonomics analysis. In vitro, L-carnitine could promote VEGF expression and NO release in cardiac microvascular endothelial cells. Therefore, we supposed L-carnitine may increase microvasuclar angiogenesis. In this study, mice coronary microembolization model with differential expression of carnitine palmitoyltransferase were developed to clarify the impact and mechanism of L-carnitine on microvascular angiogenesis and myocardial metabolism. Meanwhile, the mechanism of L-carnitine on microvascular endothelial cells’ growth and angiogenesis was also clarified in vitro level. Finally, we will elaborate the role of L-carnitine on microvascular occlusion and cardiac events on coronary no reflow patients after primary coronary intervention. Above all, these things will provide novel evidence for the diagnosis and treatment of coronary microvascular dysfunction.