PDF(Pubmed)
Abstract：
Deep vein thrombosis (DVT) is a type of venous thromboembolism and a clinically complex vascular disease. Oxidative stress serves a key role in the pathogenesis of numerous cardiovascular diseases, particularly in endothelial dysfunction-associated syndromes. Nuclear factor erythroid-2-like 2(Nrf2) transcription factor is the primary regulator of antioxidant responses. The levels of reactive oxygen species (ROS) are regulated by Nrf2 and its suppressor protein Kelch-like ECH-associated protein 1 (Keap1). However, to the best of our knowledge, genetic abnormalites in the Nrf2/Keap1 pathway in DVT syndrome have not been thoroughly investigated. The aim of the present study was to investigate the association between the Nrf2/Keap1 pathway and antioxidant responses in DVT. Mutations and expression levels of genes involved in the Nrf2/Keap1 pathway were measured in 27 patients with DVT via DNA sequencing analysis and reverse transcription-quantitative PCR, respectively. The Polymorphism Phenotyping v2 program was used to identify the pathogenic mutations. Total antioxidant activity levels were determined by measuring the effect of serum samples from 27 patients with DVT on oxidation of the 2,2\'-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid) system. A total of 23 mutations, including seven novel mutations, were detected in the Nrf2/Keap1 pathway in 24 (89%) of the 27 patients with DVT. Keap1 mRNA expression levels were significantly higher compared with Nrf2 expression levels in patients with DVT (P=0.02). Analysis of molecular characteristics and gene expression levels demonstrated that Nrf2/Keap1-associated mutations and total antioxidant levels can be used as precursor markers in the diagnosis of DVT.
摘要：
深静脉血栓形成（DVT）是一种静脉血栓栓塞，是临床上复杂的血管疾病。氧化应激在许多心血管疾病的发病机制中起着关键作用。特别是在内皮功能障碍相关综合征中。核因子类红细胞2（Nrf2）转录因子是抗氧化反应的主要调节因子。活性氧（ROS）的水平受Nrf2及其抑制蛋白Kelch样ECH相关蛋白1（Keap1）的调节。然而,据我们所知,DVT综合征中Nrf2/Keap1通路的遗传异常尚未得到彻底研究。本研究的目的是研究DVT中Nrf2/Keap1通路与抗氧化反应之间的关系。通过DNA测序分析和逆转录-定量PCR检测27例DVT患者Nrf2/Keap1通路相关基因的突变和表达水平。分别。多态性表型化v2程序用于鉴定致病性突变。通过测量27例DVT患者的血清样品对2,2\'-叠氮基双（3-乙基苯并噻唑啉-6-磺酸）系统氧化的影响来确定总抗氧化活性水平。共有23个突变,包括七个新的突变，在27例DVT患者中，有24例（89％）在Nrf2/Keap1通路中检测到。DVT患者Keap1mRNA表达水平明显高于Nrf2表达水平(P=0.02)。分子特征和基因表达水平分析表明，Nrf2/Keap1相关突变和总抗氧化剂水平可作为诊断DVT的前体标志物。
