动脉粥样硬化斑块(AS)破裂是急性冠脉综合征的主要病理机制。IncRNA被认为在AS进展中具有重要作用，巨噬细胞在AS破裂过程中发挥至关重要作用。IncRNAs是否通过调控破裂斑块内巨噬细胞活性，从而影响斑块破裂过程? 至今尚不清楚。我们前期发现IncRNA-CRNDE可上调巨噬细胞MMP-2及MMP-9表达。因此，我们推测CRNDE可能通过调控MMP-2及MMP-9表达从而参与斑块破裂，并可能与 NF-kB、 MAPK等信号转导途径有关。光学相干断层成像是血管内分辨率最高影像技术，能准确判断斑块破裂及巨噬细胞。我们课题将利用光学相干断层成像、虚拟组织学及声学造影等多种先进影像模式并结合基因转染、基因沉默、Western blot、原位杂交及RT-PCR等技术，从细胞到整体水平研究CRNDE对巨噬细胞及AS斑块破裂的作用及其机制。本课题将从新视觉阐明斑块破裂机制,并为AS治疗提供新靶点。

Atherosclerotic plaque rupture with luminal thrombosis is the most common mechanism responsible for the majority of acute coronary syndromes and sudden coronary death. Long noncoding RNAs(IncRNAs) have been recognized to play diverse and important roles in atherosclerotic plaque progression and plaque rupture. However, the functional role of lncRNAs in atherosclerotic plaque rupture is less well known. Macrophage plays a major role in all phases of atherosclerosis including plaque rupture and subsequent thrombus formation. Our experimental data have indicated that IncRNA-CRNDE can up-regulate the expression of MMP-2/MMP-9 in THP-1 monocyte-derived macrophages. Therefore, we postulate that CRNDE can regulate the pathological process of plaque rupture by up-regulating the expression of MMP-2/MMP-9 in macrophage, this is a novel mechanism for plaque rupture and possibly relates to the NF-kappaB activation and MAPK signalling pathway. Recently, intravascular optical coherence tomography (OCT), a high-resolution coronary imaging modality, with an axial resolution of approximately 10μm, has been introduced into the clinical setting. OCT can provide information about the microstructure of the coronary artery and has been shown to be capable of detailed tissue characterization. In this study, we will employ a wide range of molecular biological techniques including gene transfection, western blotting and quantitative RT-PCR. In addition, multiple advanced imaging modalities including optical coherence tomography, virtual-histology and acoustic contrast will be performed to investigate the effect of IncRNA-CRNDE on plaque progression and to disclose the mechanism of the macrophage activiation by CRNDE. Our results may provide a new therapeutic target of the pharmacological intervention to atherosclerosis.