斑块内血管生成促进动脉粥样硬化斑块不稳定。利用稳定斑块的化学小分子3BDO，我们新发现斑块内血管生成过程中，内皮细胞异源性核糖核蛋白E1（hnRNPE1）总蛋白及丝氨酸水平上调，但其作用及作用机制尚未搞清。HnRNPE1既是一个转录促进因子也是一个翻译调节因子，利用oxLDL体外模拟斑块内血管生成，我们发现此过程中转录抑制因子Hmbox1的蛋白水平显著下调，而促血管生成因子profilin1和cofilin1的mRNA和蛋白水平显著上调。敲低hnRNPE1或过表达Hmbox1均能抑制oxLDL诱导的血管生成以及profilin1和cofilin1水平的上调。我们推测hnRNPE1可能通过Hmbox1促进profilin1和cofilin1的表达，也可能直接靶向profilin1和cofilin1调控两者的表达，进而促进斑块内血管生成。本项目我们拟证明该假设，为动脉粥样硬化的治疗提供新线索。

Neovascularization in atherosclerotic lesions promote plaque expansion, intraplaque hemorrhage and rupture, which play critical roles in the pathogenesis of heart attacks and strokes. By using a small chemical molecule 3BDO, which could stabilize atherosclerotic lesions in ApoE-/- mice, we found the total protein level and serine phosphorylation level of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) in vascular endothelial cells increased during the neovascularization in atherosclerotic lesions. However, the role and the mechanisms of hnRNP E1 regulating angiogenesis in atherosclerotic lesions have not yet been clarified. HnRNP E1 is a transcriptional activator and translational regulatory factor. In the pre-experiments, oxidized low-density lipoprotein（oxLDL）, an atherosclerosis induced factor, promoted in vitro angiogenesis in HUVECs to mimic angiogenesis in atherosclerotic lesions. We found in the oxLDL-activated HUVECs，the transcriptional repressor Hmbox1 protein level decreased, and proangiogenic factors profilin1 and cofilin1 mRNA and protein levels increased. Moreover，knock down hnRNP E1 or overexpress Hmbox1 in HUVECs could inhibit oxLDL-induced angiogenesis and profilin1 and cofilin1 levels. We hypothesized that hnRNP E1 might promote the profilin1 and cofilin1 expression through Hmbox1 or directly targeting these two genes, and thus promote the neovascularization in atherosclerotic lesions. In this research, we will verify our hypothesis by using 3BDO and molecular biology and cell biology experimental technologies. By these researches, we will provide evidence for explaining new signal pathways of angiogenesis in atherosclerotic lesions mediated by hnRNP E1, and discover new target for therapy of atherosclerosis.