Increased serum high-mobility group box-1 and cleaved receptor for advanced glycation endproducts levels and decreased endogenous secretory receptor for advanced glycation endproducts levels in diabetic and non-diabetic patients with heart failure
Increased serum high-mobility group box-1 and cleaved receptor for advanced glycation endproducts levels and decreased endogenous secretory receptor for advanced glycation endproducts levels in diabetic and non-diabetic patients with heart failure
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DOI：
10.1093/eurjhf/hfq231
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发表时间：
2011-04-01
影响因子：
18.2
通讯作者：
Shen, Wei Feng
中科院分区：
文献类型：
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作者：
Wang, Ling Jie;Lu, Lin;Shen, Wei Feng
高迁移率族蛋白1（HMGB 1）是糖基化终产物受体的配体。HMGB 1-β 2相互作用与心功能不全有关。我们评估了HMGB 1和RAGE亚型与糖尿病和非糖尿病患者心力衰竭（HF）的相关性。方法和结果我们检测了血清HMGB 1、切割RAGE（cRAGE）、内源性分泌RAGE（esRAGE）、高敏C反应蛋白（hsCRP）、和N-末端脑钠肽前体在125例糖尿病和222例非糖尿病慢性心力衰竭中国患者中，同时评估NT-proBNP水平和左心室容积和功能。其中，79例无HF的糖尿病患者和220例正常受试者分别作为糖尿病和正常对照。HF患者的血清HMGB 1、cCRP、hsCRP和NT-proBNP水平高于非HF受试者，而esp水平低于非HF受试者（全部; P < 0.01），糖尿病HF患者的cCRP和hsCRP水平高于非糖尿病HF患者（P < 0.01）。对于合并或不合并糖尿病的心力衰竭患者，HMGB 1水平与左心室舒张末期和收缩末期容积（分别为r = 0.267和r = 0.321）和NT-proBNP值（r = 0.497）正相关，与射血分数呈负相关（r = -0.461;所有P < 0.001）。血清CRP水平与NT-proBNP值（r = 0.451）和纽约心脏协会心功能分级（r = 0.402;均P < 0.001）相关。多因素回归分析显示，糖尿病和非糖尿病心衰患者血清HMGB 1、CRP、ET水平均与心衰的严重程度相关。结论糖尿病和非糖尿病心衰患者血清HMGB 1、CRP水平升高，ET水平降低，与心衰的严重程度相关。这种关联值得进一步研究。
Aims High-mobility group box-1 (HMGB1) is a ligand for the receptor for advanced glycation endproducts (RAGE). An HMGB1-RAGE interaction has been implicated in cardiac dysfunction. We assessed the association of HMGB1 and RAGE isoforms with heart failure (HF) in diabetic and non-diabetic patients.Methods and results We assayed serum levels of HMGB1, cleaved RAGE (cRAGE), endogenous secretory RAGE (esRAGE), high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in parallel with assessment of left ventricular volumes and function in 125 diabetic and 222 non-diabetic Chinese patients with chronic HF. Of the total, 79 diabetic patients without HF and 220 normal subjects served as diabetic and normal controls, respectively. Serum HMGB1, cRAGE, hsCRP, and NT-proBNP levels were higher and, in contrast, esRAGE levels lower in HF patients than in subjects without HF (for all; P < 0.01), with higher levels of cRAGE and hsCRP in diabetic HF vs. non-diabetic HF patients (P < 0.01). For HF patients-with or without diabetes-HMGB1 levels correlated positively with left ventricular end-diastolic and end-systolic volumes (r = 0.267 and r = 0.321, respectively) and NT-proBNP values (r = 0.497), and were inversely related to ejection fraction (r = -0.461; all P < 0.001). Serum cRAGE levels correlated with NT-proBNP values (r = 0.451) and New York Heart Association functional class (r = 0.402; both P < 0.001). Multivariable regression analysis revealed that HMGB1, cRAGE, and esRAGE were consistently associated with HF in diabetic and non-diabetic patients.Conclusion Heart failure patients have increased serum HMGB1 and cRAGE and decreased esRAGE levels, and these are related to the severity of HF in both diabetic and non-diabetic patients. Such associations are worth further investigation.