我们发现糖化载脂蛋白apoA-I促进炎症、内皮胰岛素抵抗和动脉粥样硬化。芯片显示，糖化apoA-I刺激内皮细胞后蛋白酪氨酸磷酸酶γ（PTPRG）及其配体contactin4显著上调。两蛋白在糖尿病动脉粥样硬化及冠脉外周脂肪组织中显著升高。实验显示，PTPRG-/-/apoE-/-小鼠动脉粥样硬化比apoE-/-小鼠降低。沉默PTPRG后，糖化apoA-I诱导的内皮胰岛素抵抗，内皮和单核巨噬细胞炎症被逆转，结合文献提示contactin 4-PTPRG介导了糖化apoA-I致病效应。后续我们将对全身敲除、内皮/巨噬细胞/脂肪细胞特异性PTPRG敲除小鼠及给予contactin 4单抗小鼠注射糖化apoA-I及对照；并刺激PTPRG敲低细胞株和原代细胞，之后检查分子细胞病理功能学改变，明确apoA-I中与上调PTPRG、contactin4及致病相关的糖化位点，阐明糖化apoA-I致病机制。

We have found that glycated apoA-I promotes inflammation, endothelial insulin resistance, and atherosclerosis in mice. After treatment of endothelial cells with glycated apoA-I, mRNA analysis showed that protein tyrosine phosphatase receptor-type gamma (PTPRG) and its ligand contactin 4 were significantly increased. This information was supported by clinical samples, showing that these two proteins elevated signifantly in atherosclerotic vessels and peri-vascular adipose tissue, and in peripheral blood mononuclear cells from CAD patients as compared with control vessels, tissues and cells. In vivo and in vitro experiments, PTPRG-/-/apoE-/- mice had significantly less atherosclerotic area in aorta than in apoE-/- mice after high-fat diet. Glycated apoA-I induced an attenuated impact on endothelial cells, macrophages regarding inflammation and insulin resistance after knockdown of PTPRG by siRNA. These results including our findings and those from literature indicate that glycated apoA-I induces inflammation and atherosclerosis through mediation of contactin4-PTPRG. In our next step, we will investigate the atherogenic effects of glycated apoA-I in global PTPRG knockout mice, and in tissue specific PTPRG knockout mice (endothelial, macrophage, and adipose tissue), with addition of contactin 4 antibody. We will also evaluate the inflammatory effects of PTPRG and contactin 4 in cells or mouse-derived cells, followed by molecular, cellular, functional and pathological examination. Glycation position of apoA-I with respect to effects of contactin 4 and PTPRG, and atherosclerosis will be deciphered. The mechanisms of glycated apoA-I-induced atherogenesis will be clarified.