RAGE基因多态性与高血压左室肥厚、血清esRAGE水平的相关性研究

目的探讨晚期糖基化终末产物受体(RAGE)基因Gly82Ser多态性与EH-LVH患者及其血清内源性分泌型RAGE(esRAGE)水平的相关性。方法应用聚合酶链反应-限制性片段多态性(PCR-RLFP)的方法,检测94例EH患者(其中38例伴LVH)及50例对照组RAGE基因Gly82Ser多态性,同时采用ELISA法测定血清esRAGE水平。结果与正常对照组相比,EH组基因型频率和等位基因频率差异无统计学意义(P>0.05);EH-LVH组RAGE基因Gly82Ser位点的GS基因型频率和82Ser等位基因频率明显增高,差异有统计学意义(P<0.05);EH-LVH和EH组Gly82Ser SS基因型血清es-RAGE水平与对照组相比差异显著(P<0.05)。结论 RAGE基因Gly82Ser多态性与EH的发生发展无关;EH-LVH患者RAGE基因Gly82Ser GS基因型和82Ser等位基因增多,提示82Ser等位基因可能是EH-LVH发病的易感基因;RAGE基因Gly82Ser多态性与血清esRAGE水平显著相关。     

Receptor for advanced glycation end products--soluble form and gene polymorphisms in chronic haemodialysis patients.

BACKGROUND: The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of vascular and inflammatory diseases. The pathological effects mediated via RAGE are physiologically inhibited by soluble RAGE (sRAGE). Our aim was to study sRAGE and RAGE gene polymorphisms in haemodialysis (HD) patients. METHODS: A total of 261 stable HD patients were enrolled in the study and prospectively followed up for 30 months. At the begining of the study, sRAGE inflammatory and nutritional parameters were determined. RAGE polymorphisms were determined in a subgroup of 214 HD patients. A group of 100 healthy controls was used for comparison. RESULTS: In HD patients, sRAGE is elevated in comparison with healthy controls (3427+/-1508 vs 1758+/-637 pg/ml, P<0.001). It correlates negatively with residual diuresis (r=-0.193, P<0.05), with the acute phase reactants fibrinogen (r=-0.174, P<0.05) and orosomucoid (r=-0.135, P<0.05) and with the leucocyte count (r=-0.158, P<0.05). On the other hand, it is not related to the presence of diabetes mellitus, cardiovascular disease, nutritional status and mortality. The highest sRAGE levels are found in -429 CC and 2184 GG polymorphisms of the RAGE gene. The same results as for sRAGE were obtained for endogenous secretory RAGE (esRAGE), which correlated significantly with sRAGE (r=0.88, P<0.001). CONCLUSION: We conclude that in HD patients, sRAGE is increased due to decreased renal function, which is a very strong determinant of sRAGE levels, and is inversely related to inflammation. The highest sRAGE levels are influenced genetically. In our study, sRAGE levels were not related to mortality of HD patients.     

Analysis of steatosis biomarkers and inflammatory profile after adding on PCSK9 inhibitor treatment in familial hypercholesterolemia subjects with nonalcoholic fatty liver disease: A single lipid center real-world experience

Background and aimsNonalcoholic fatty liver disease (NAFLD) may be crucial in subjects with familial hypercholesterolemia (FH). We aimed to evaluate the effect of the inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9-i) on steatosis biomarkers such as triglyceride-glucose index (TyG) and hepatic steatosis index (HSI) and analyse the role of TG/HDL in this population before and after adding-on PCSK9-i.Methods and resultsIn this observational study, we evaluated 26 genetically confirmed FH patients with NAFLD and an LDL-C off-target despite high-intensity statins plus ezetimibe. All patients added PCSK9-i treatment and obtained biochemical analysis and TyG and HSI evaluation at baseline and after six months of PCSK9-i. No difference of steatosis biomarkers was found after adding-on PCSK9-i therapy. In a secondary analysis, we divided the study population in two groups according to TG/HDL median value: high TG/HDL group (H-TG/HDL) and low TG/HDL group (L-TG/HDL). TyG and HSI were significantly lower in the L-TG/HDL than H-TG/HDL group (for TyG 9.05 ± 0.34 vs 9.51 ± 0.32; for HSI 38.43 ± 1.35 vs 41.35 ± 1.83, p value for both < 0.05). After six months of PCSK9-i therapy, TyG and HSI were significantly reduced in the L-TG/HDL group after PCSK9-i therapy (?7.5% and ?8.4% respectively, p value for both < 0.05) and these biomarkers were lower compared to H-TG/HDL group (for TyG 8.37 ± 0.14 vs 9.19 ± 0.12; for HSI 35.19 ± 1.32 vs 39.48 ± 1.33, p value for both < 0.05).ConclusionIn conclusion, PCSK9-i therapy significantly ameliorate steatosis biomarkers in FH patients with low TG/HDL; our results appear to be consistent with a beneficial role of PCSK9-i on steatosis biomarkers in FH subjects with NAFLD.     

Decreased serum esRAGE level is associated with angiographically determined coronary plaque progression in diabetic patients

Objective

This study evaluated the relationship between serum levels of endogenous secretory receptor for advanced glycation endproducts (esRAGE) and coronary plaque progression in diabetic and nondiabetic patients.

Design and methods

Serum esRAGE level was measured and quantitative coronary angiography (QCA) was performed in 265 consecutive patients at baseline and 1-year follow-up.

Results

Comparing to baseline, serum esRAGE level was significantly increased during follow-up in nondiabetic patients without plaque progression (p = 0.014), unchanged in nondiabetic patients with plaque progression and diabetic patients without plaque progression, and decreased in diabetic patients with plaque progression (p = 0.011). Moreover, change of esRAGE levels correlated with change of QCA measurements. Multivariable regression analyses revealed that high-density lipoprotein cholesterol (OR = 0.214, p = 0.037), hypertension (OR = 2.755, p = 0.011), high-sensitivity C-reactive protein (OR = 1.083, p < 0.001) and change of esRAGE (OR = 23.477, p < 0.001) were independent risk factors for plaque progression in diabetic patients.

Conclusions

This study demonstrated an association of decreased serum esRAGE level with coronary plaque progression in patients with diabetes.     

晚期糖基化终产物受体在心房颤动患者血清中的表达及意义

目的探讨心房颤动（AF）患者血清高迁移率族蛋白1（HMGB1）、晚期糖基化终产物内源性分泌受体（es-RAGE）及晚期糖基化终产物C端短截受体（cRAGE）水平的变化。方法本研究收集我院连续入院的75例AF患者,另外纳入32例年龄和性别与AF组相匹配的健康查体者作为对照组。采用ELISA法检测两组人群血清HMGB1、cRAGE及esRAGE水平。结果阵发性AF组及持续性AF组HMGB1水平高于对照组（均P〈0.05）;持续性AF组HMGB1水平高于阵发性AF组（P〈0.05）。阵发性AF组及持续性AF组cRAGE水平高于对照组（均P〈0.05）;持续性AF组cRAGE水平高于阵发性AF组（P〈0.05）。阵发性AF组及持续性AF组esRAGE水平低于对照组（均P〈0.05）;持续性AF组esRAGE水平低于阵发性AF组（P〈0.05）。结论本研究显示持续性和阵发性AF患者血清HMGB1和cRAGE水平显著升高,而esRAGE水平显著降低,提示cRAGE和esRAGE可能成为AF的两种新型生物标记物,且可能与HMGB1共同参与了AF发生的病理生理过程。     

Endogenous secretory RAGE increases with improvements in body composition and is associated with markers of adipocyte health

Background and aims

The receptor for advanced glycation end products (RAGE) is implicated in obesogenesis. Conversely, soluble RAGE (sRAGE) competitively inhibits RAGE. Our aim was to determine the effects of weight-loss via alternate day fasting (ADF) on sRAGE isoforms and evaluate potential relationships with body composition.

抑郁症患者血清S100B蛋白及其分泌型糖基化终产物受体的研究

目的 探讨首发和复发抑郁症患者血清S100B蛋白及其分泌型糖基化终产物受体(esRAGE)浓度的改变.方法 采用酶联免疫方法检测34例抑郁症患者(首发15例,复发19例) 和34名正常对照的血清S100B、esRAGE蛋白浓度,比较患者组和对照组间的差异;采用17项汉密尔顿抑郁量表(Hamilton Depression Rating Scale-17,HAMD-17)评定患者的症状,分析上述两个生化指标与症状之间的关系.结果 总体患者组血清S100B浓度高于对照组[(0.57±0.04) ng/mL vs(0.38±0.12)ng/mL,P<0.01],esRAGE浓度低于对照组[(0.52±0.11) ng/mL vs(0.66±0.10)ng/mL,P<0.01];首发和复发患者组之间血清S100B浓度与esRAGE的差异均有统计学意义[(0.46±0.01) ng/mL vs(0.57±0.02)ng/mL,P<0.01;(0.44±0.02)ng/mL vs(0.53±0.10)ng/mL,P<0.01];与对照组相比,首发及复发患者组的血清S100B浓度均升高而esRAGE浓度均下降,差异均有统计学意义(P<0.01).未见患者组的血清S100B、esRAGE浓度相关或二者与HAMD评分相关(P>0.05).结论 血浆S100B、esRAGE可能在抑郁症的发病中起了一定的作用,复发患者神经胶质细胞分泌S100B能力可能更强.     

Endogenous secretory receptor for advanced glycation endproducts as a novel prognostic marker in chondrosarcoma

BACKGROUND: Chondrosarcoma, the second most frequent primary malignant bone tumor, is classified into 3 grades according to histologic criteria of malignancy. However, a low-grade lesion can be difficult to distinguish from a benign enchondroma, whereas some histologically low-grade lesions may carry a poor prognosis. The receptor for advanced glycation endproducts (RAGE) and its ligand, high-mobility group box-1 (HMGB1), was quantified in enchondromas and chondrosarcomas to determine whether these markers were associated with histological malignancy and prognosis. METHODS: Enchondromas (n = 20) and typical chondrosarcomas (n = 39) were evaluated for RAGE, endogenous secretory RAGE (esRAGE, a splice variant form), and HMGB1 protein expression by immunohistochemistry including laser confocal microscopy. The content of esRAGE in resected specimens was measured with an enzyme-linked immunosorbent assay. Associations of these molecules with histology and clinical behavior of tumors were analyzed. RESULTS: Expression of esRAGE and HMGB1 was observed in all specimens. The numbers of cells positive for esRAGE and HMGB1 expression were positively associated with histologic grade. Expression of esRAGE was significantly higher in chondrosarcomas than in enchondromas (P < .001). Tissue esRAGE content was also significantly higher in grade 1 and 2 chondrosarcomas than enchondromas (P = .0255 and P = .008, respectively). High expression of esRAGE in grade 1 chondrosarcoma was associated with subsequent recurrence (P = .0013), lung metastasis (P = .0071), and poor survival (P < .001). CONCLUSIONS: Assessment of esRAGE expression should aid in diagnostic and prognostic determinations in chondrosarcoma.