Mononuclear phagocytes(MP)comprise a family of cells that include microglial cells(MC),monocytes,and macrophages.The subretinal space,located between the RPE and the photoreceptor outer segments,is physiologically dev...Mononuclear phagocytes(MP)comprise a family of cells that include microglial cells(MC),monocytes,and macrophages.The subretinal space,located between the RPE and the photoreceptor outer segments,is physiologically devoid of MPs and a zone of immune privilege mediated,among others,by immunosuppressive RPE signals.Age-related macular degeneration(AMD)is a highly heritable major cause of blindness,characterized by a breakdown of the subretinal immunosuppressive environment and an accumulation of pathogenic inflammatory MPs.Studies in mice and humans suggest that the AMD-associated APOE2 isoform promotes the breakdown of subretinal immunosuppression and increased MP survival.Of all genetic factors,variants of complement factor H(CFH)are associated with greatest linkage to AMD.Using loss of function genetics and orthologous models of AMD,we provide mechanistic evidence that CFH inhibits the elimination of subretinal MPs.Importantly,the AMD-associated CFH402H isoform markedly increased this inhibitory effect on microglial cells,indicating a causal link to disease etiology.Pharmacological acceleration of resolution of subretinal inflammation might be a powerful tool for controlling inflammation and neurodegeneration in late AMD.展开更多
目的研究血浆补体因子H(CFH)、超敏C反应蛋白(hsCRP)和胰岛素抵抗(IR)与冠心病(CAD)关系。方法采用JUdkins法行冠状动脉造影(CAG),排除冠心病(非冠心病组)204例,确诊冠心病155例。其中,冠脉病变血管1支组80例、2支组41例、3支组34例;按...目的研究血浆补体因子H(CFH)、超敏C反应蛋白(hsCRP)和胰岛素抵抗(IR)与冠心病(CAD)关系。方法采用JUdkins法行冠状动脉造影(CAG),排除冠心病(非冠心病组)204例,确诊冠心病155例。其中,冠脉病变血管1支组80例、2支组41例、3支组34例;按临床亚型可分稳定型心绞痛(SA)组62例、不稳定型心绞痛(UA)组69例和心肌梗死(MI)组24例。应用酶联免疫法测定血浆CFH浓度、Backman生化分析仪测定hsCRP、空腹血糖、胰岛素和血脂等指标。根据HOMA Model计算IR指数(IRI)。结果冠心病组IRI明显高于非冠心病组(3.89±1.89 vs 3.40±1.80)(P<0.05),MI组IRI(4.39±2.62)、UA组IRI(4.36±1.61)均明显高于SA组(3.19±1.14),(P<0.05);校正年龄、性别、吸烟史、高血压史和冠心病家族史后,hsCRP是冠心病的独立危险因素(OR:1.417,95%CI:1.236～1.625,P<0.05);IR与hsCRP的相关系数r为0.186,P<0.01。血浆CFH浓度在组间无差别。三个指标在不同病变血管支数组中没有差别。结论hsCRP为冠心病的独立危险因子,IR可以预测冠心病,CFH与冠心病无关。展开更多
文摘Mononuclear phagocytes(MP)comprise a family of cells that include microglial cells(MC),monocytes,and macrophages.The subretinal space,located between the RPE and the photoreceptor outer segments,is physiologically devoid of MPs and a zone of immune privilege mediated,among others,by immunosuppressive RPE signals.Age-related macular degeneration(AMD)is a highly heritable major cause of blindness,characterized by a breakdown of the subretinal immunosuppressive environment and an accumulation of pathogenic inflammatory MPs.Studies in mice and humans suggest that the AMD-associated APOE2 isoform promotes the breakdown of subretinal immunosuppression and increased MP survival.Of all genetic factors,variants of complement factor H(CFH)are associated with greatest linkage to AMD.Using loss of function genetics and orthologous models of AMD,we provide mechanistic evidence that CFH inhibits the elimination of subretinal MPs.Importantly,the AMD-associated CFH402H isoform markedly increased this inhibitory effect on microglial cells,indicating a causal link to disease etiology.Pharmacological acceleration of resolution of subretinal inflammation might be a powerful tool for controlling inflammation and neurodegeneration in late AMD.
文摘目的研究血浆补体因子H(CFH)、超敏C反应蛋白(hsCRP)和胰岛素抵抗(IR)与冠心病(CAD)关系。方法采用JUdkins法行冠状动脉造影(CAG),排除冠心病(非冠心病组)204例,确诊冠心病155例。其中,冠脉病变血管1支组80例、2支组41例、3支组34例;按临床亚型可分稳定型心绞痛(SA)组62例、不稳定型心绞痛(UA)组69例和心肌梗死(MI)组24例。应用酶联免疫法测定血浆CFH浓度、Backman生化分析仪测定hsCRP、空腹血糖、胰岛素和血脂等指标。根据HOMA Model计算IR指数(IRI)。结果冠心病组IRI明显高于非冠心病组(3.89±1.89 vs 3.40±1.80)(P<0.05),MI组IRI(4.39±2.62)、UA组IRI(4.36±1.61)均明显高于SA组(3.19±1.14),(P<0.05);校正年龄、性别、吸烟史、高血压史和冠心病家族史后,hsCRP是冠心病的独立危险因素(OR:1.417,95%CI:1.236～1.625,P<0.05);IR与hsCRP的相关系数r为0.186,P<0.01。血浆CFH浓度在组间无差别。三个指标在不同病变血管支数组中没有差别。结论hsCRP为冠心病的独立危险因子,IR可以预测冠心病,CFH与冠心病无关。
