In vivo and in vitro studies establishing haptoglobin as a major susceptibility gene for diabetic vascular disease.
In vivo and in vitro studies establishing haptoglobin as a major susceptibility gene for diabetic vascular disease.
复制标题
在体内和体外研究中，建立抗乳果蛋白是糖尿病血管疾病的主要易感基因。
DOI：
10.2147/vhrm.1.1.19.58930
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发表时间：
2005
影响因子：
2.9
通讯作者：
Levy, Andrew P
中科院分区：
文献类型：
--
作者：
Asleh, Rabea;Levy, Andrew P
在溶血过程中释放的血红蛋白（Hb）是一种强效氧化剂。红细胞外Hb可进入血管壁，介导低密度脂蛋白氧化，从而促进动脉粥样硬化的发生和发展。触珠蛋白（Hp）是一种抗氧化蛋白，因为它能够结合Hb并阻断Hb诱导的氧化损伤。Hp也通过CD163巨噬细胞清道夫受体促进Hb从血管外腔室的清除。在人类中，Hp有两个常见的等位基因，分别为1和2，相应地，有三种不同的可能的基因型：Hp1-1、Hp2-1和Hp2-2。我们最近在几项纵向研究中证明，Hp基因型是糖尿病血管并发症的独立危险因素。具体来说，我们已经表明，与Hp2-1或Hp1-1的糖尿病患者相比，Hp 2-2的糖尿病患者更容易发生肾病、视网膜病变和心血管疾病。在机制上，我们发现不同Hp蛋白类型在抗氧化和cd163介导的清除和激活功能上存在显著差异。此外，我们已经证明这些功能在糖尿病状态下被修改。本文就Hp多态性与糖尿病血管并发症的相关临床研究及其相互作用的分子基础进行综述。
Hemoglobin (Hb) released during hemolysis is a potent oxidant. Extracorpuscular Hb may enter the vessel wall and mediate low-density lipoprotein oxidation, thereby promoting the development and progression of atherosclerosis. Haptoglobin (Hp) is an antioxidant protein as a result of its ability to bind Hb and block Hb-induced oxidative damage. Hp also facilitates the removal of Hb from the extravascular compartment via the CD163 macrophage scavenger receptor. In man, there are two common alleles for Hp denoted 1 and 2, and correspondingly, three different possible genotypes: Hp1-1, Hp2-1, and Hp2-2. We have recently demonstrated in several longitudinal studies that Hp genotype is an independent risk factor for diabetic vascular complications. Specifically, we have shown that diabetic individuals with Hp 2-2 are more likely to develop nephropathy, retinopathy, and cardiovascular disease as compared with those with Hp2-1 or Hp1-1. Mechanistically, we have found significant Hp type differences in the antioxidant and CD163-mediated scavenging and activation functions of the different Hp protein types. Furthermore, we have demonstrated that these functions are modified in the diabetic state. In this review, we focus on the clinical studies associating the Hp polymorphism and diabetic vascular complications, and the molecular basis behind this interaction.