Fibulin-1 Is a Marker for Arterial Extracellular Matrix Alterations in Type 2 Diabetes
Fibulin-1 Is a Marker for Arterial Extracellular Matrix Alterations in Type 2 Diabetes
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DOI：
10.1373/clinchem.2011.162966
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发表时间：
2011-11-01
影响因子：
9.3
通讯作者：
Rasmussen, Lars Melholt
中科院分区：
文献类型：
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作者：
Cangemi, Claudia;Skov, Vibe;Rasmussen, Lars Melholt
背景技术背景：细胞外基质的改变是糖尿病动脉变化的重要因素，与血管僵硬度增加和心血管疾病的发展有关。然而，没有生物标志物糖尿病相关的动脉变化已被defined.METHODS：乳腺动脉标本从17名男性2型糖尿病和18个非糖尿病个体被用于微阵列表达谱，定量实时PCR，免疫测定和免疫组化分析。一个衍生的候选标记物，fibulin-1，这是一种弹性蛋白相关的基质分子，在血浆中进行免疫化学测定，这些血浆来自（a）70名预定进行血管手术的患者，（B）305名接受颈动脉超声和超声心动图检查的2型糖尿病患者，和（c）308名2型糖尿病患者，随访15年。2型糖尿病患者非动脉粥样硬化动脉组织中上调最多的转录本编码细胞外基质蛋白，fibulin-1。糖尿病患者动脉提取物中的fibulin-1蛋白浓度高于非糖尿病患者，糖尿病动脉外弹性膜周围fibulin-1免疫染色明显增加。糖尿病患者血浆fibulin-1浓度升高（P = 0.006）。血浆fibulin-1浓度与血红蛋白A（1c）相关（P < 0.001），动脉硬化指数包括脉压（P < 0.001），颈动脉顺应性（P = 0.004），以及血浆N末端B型利钠肽前体浓度（P < 0.001），并预测15年死亡率（P = 0.013）。Fibulin-1在2型糖尿病患者的动脉壁和血浆中积累，并且似乎是与2型糖尿病中动脉细胞外基质变化相关的因子。(C)2011年美国临床化学协会
BACKGROUND: Extracellular matrix alterations are important elements in the arterial changes seen in diabetes, being associated with increased vascular stiffness and the development of cardiovascular diseases. However, no biomarkers for diabetes-related arterial changes have been defined.METHODS: Mammary artery specimens from 17 men with type 2 diabetes and 18 nondiabetic individuals were used for microarray expression profiling, quantitative real-time PCR, immunoassay, and immunohistochemical analyses. A derived candidate marker, fibulin-1, which is an elastin-associated matrix molecule, was measured immunochemically in plasma from (a) 70 patients scheduled for vascular surgery, (b) 305 patients with type 2 diabetes examined with carotid ultrasonography and echocardiography, and (c) 308 patients with type 2 diabetes, followed for 15 years.RESULTS: The most upregulated transcript in nonatherosclerotic arterial tissue from patients with type 2 diabetes encoded the extracellular matrix protein, fibulin-1. Higher concentrations of fibulin-1-protein were present in artery extracts from patients with diabetes than extracts from individuals without diabetes, and increased fibulin-1 immunostaining was apparent around the external elastic lamina of diabetic arteries. Patients with diabetes displayed increased plasma concentrations of fibulin-1 (P = 0.006). Plasma fibulin-1 concentrations correlated with hemoglobin A(1c) (P < 0.001), arterial stiffness indices including pulse pressure (P < 0.001), and carotid compliance (P = 0.004), as well as plasma N-terminal pro-B-type natriuretic peptide concentrations (P < 0.001) and were predictive of 15-year mortality (P = 0.013).CONCLUSIONS: Fibulin-1 accumulates in the arterial wall and in plasma of patients with type 2 diabetes, and appears to be a factor associated with arterial extracellular matrix changes in type 2 diabetes. (C) 2011 American Association for Clinical Chemistry