动脉硬化疫苗和抗体治疗研究已经有广泛的报道。我们应用动脉硬化病人的血清筛选12氨基酸肽库，首次发现动脉硬化相关抗原-胶原蛋白VI（Collagen VI， CVI）。同时利用动脉硬化病人B细胞建立抗体基因库，筛选CVI获得全人抗体。在ApoE-/-小鼠动物模型上CVI抗体治疗获得使斑块面积退缩50%以上的治疗效果。研究发现，CVI抗体能够使炎症性的单核巨噬细胞（M1型）向吞噬转运脂质的M2型分化。CVI抗体激活FcgammaRIIB受体下游的SHIP/DOK，抑制ERK和JNK的激活（M1型分化是MAPKs依赖性的），从而抑制oxLDL诱导的M1型巨噬细胞分化。本项课题旨在研究CVI抗体抑制M1型巨噬细胞的分化、抑制oxLDL诱导的细胞凋亡、促进其吞噬功能、表达转脂蛋白ABCA1将吞噬的脂质交给高密度脂蛋白（HDL），从而经胆固醇反转运途径将吞噬的脂质经肠道排出体外的分子机制。

Atherosclerosis (As) has been regarded as an autoimmune disease. It has been reported that both vaccine and antibody adoptive transfer had either preventive or therapeutic effect. By using As patients’ plasma screening a 12 amino-acid peptide library, we first found a new AS-related antigen – collagen VI (CVI). And using As patients’ B cells, we made a antibody library and screened and made a full length human antibody against CVI. These antibodies have been proved to induce the regression of atherosclerotic plaque area 50% on high fat diet-induced ApoE-/- animal model. Further studies indicated that, CVI antibodies significantly induced monocytes/macrophages differentiation, from inflammatory M1 to M2, and M2 has better uptake and transfer lipids function. CVI antibodies specifically activate macrophages FcgammaRIIB and ensuing SHIP/DOK signal transduction pathway, which is a negative activation pathway only in Fcgamma Receptors (the others are FcgammaRI and RIII, which they all are activation receptors). We also found oxLDL induced M1 differentiation is MAPKs dependent, which includes p38, ERK, and JNK MAPKs. While, CVI antibodies indeed specifically inactivated ERK and JNK, but not p38, though activation of FcgammaRIIB signal transduction pathway (FcgammaRIIB→SHIP/DOK), so that CVI antibodies inhibited M1 differentiation. This project mainly explore the molecular mechanism on CVI-induced inhibition of M1 differentiation, the inhibition of oxLDL-induced macrophages apoptosis, the induction of macrophage lipid uptake function and expression of cellular lipid transfer protein ABCA1, which could help transfer the macrophages lipids to HDL protein, ApoAI. So that lipid uptake by macrophages might be able to be excreted to the outside of the body from intestine through cholesterol reverse transfer pathway. Part of this project results has been awarded a “Young Investigator Award” in the XVIII congress of the international society of atherosclerosis in 2018, in Toronto.