Haptoglobin genotype and the iron hypothesis of atherosclerosis.
Haptoglobin genotype and the iron hypothesis of atherosclerosis.
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触珠蛋白基因型和动脉粥样硬化的铁假说。
DOI：
10.1016/j.atherosclerosis.2011.01.029
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发表时间：
2011
期刊：
影响因子：
5.3
通讯作者：
Levy,AndrewP
中科院分区：
文献类型：
--
作者：
Viener,HillaLee;Levy,AndrewP
杰罗姆沙利文在30年前首次提出缺铁可能对缺血性心脏病的发展有保护作用[1]。这一假说的热情被一系列的研究所抑制，这些研究未能表明常规的全身铁状态测量与人类动脉粥样硬化的增加有关，然而，这些研究中未能证明铁与动脉粥样硬化之间的联系的一个潜在原因可能是由于未能关注铁的分子形式，而铁的分子形式最有可能引起动脉粥样硬化。铁是进行氧化修饰的合理候选物，氧化修饰被认为在动脉粥样硬化过程中至关重要[2]。在生理条件下，铁能够产生高活性的标记氧自由基，如超氧自由基和羟基自由基。然而，我们体内的大部分铁被储存在专业的铁结合蛋白转铁蛋白或铁蛋白上，其中铁是氧化还原惰性的，不能诱导底物氧化。在过去的10年中，人们已经认识到，存在一个小的但严格调节的铁池，其不与转铁蛋白或铁蛋白结合，并且具有氧化还原活性（称为不稳定血浆非转铁蛋白结合铁或NTBI）[3，4]。NTBI代表了许多分子种类，其中很少有已被确定。已经鉴定的一种类型的NTBI是包含在触珠蛋白-血红蛋白复合物中的铁[5]。触珠蛋白（Hp）是一种丰富的血浆蛋白，其以高亲和力结合血红蛋白[6]。虽然血红蛋白中的血红素铁是一种非常有效的氧化剂，但Hp与血红蛋白的结合可降低血红蛋白中铁进行氧化反应的能力[7]。在人类中，在Hp遗传基因座上存在两种可能的等位基因，记为1和2。Hp 2等位基因的蛋白产物在阻断由铁衍生的血红蛋白介导的氧化反应的能力上是有缺陷的。因此，虽然Hp 1-Hb复合物相对氧化还原惰性，但Hp 2-Hb复合物根据定义含有非转铁蛋白结合的氧化还原活性铁[5]。
Jerome Sullivan first proposed 30 years ago that iron deficiency may be protective against the development of ischemic heart disease [1]. Enthusiasm for this hypothesis was dampened by a series of studies which failed to show that conventional measurements of total body iron status were associated with increased atherosclerosis in man. However, one potential reason for the failure to demonstrate an association between iron and atherosclerosis in these studies may have been due to a failure to focus on the molecular form of iron which is most likely responsible for inducing atherosclerosis. Iron is a reasonable candidate for carrying out the oxidative modifications which are believed to be paramount in the atherosclerotic process [2]. Iron is capable of generating highly reactive label oxygen free radicals such as superoxide radical and hydroxyl radical under physiological conditions. However, most of the iron in our bodies is stored bound to professional iron binding proteins-transferrin or ferritin-in which the iron is redox inactive and not capable of inducing oxidation of substrates. Over the past 10 years it has become appreciated that there exists a small but tightly regulated pool of iron which is not bound to transferrin or ferritin and which is redox active (referred to as labile plasma non-transferrin bound iron or NTBI)[3, 4]. NTBI represents a number of molecular species very few of which have been identified. One type of NTBI which has been identified is the iron contained within the Haptoglobin-hemoglobin complex [5].Haptoglobin (Hp) is an abundant plasma protein which binds with high affinity to hemoglobin [6]. While the heme iron in hemoglobin is a very potent oxidant, the binding of Hp to hemoglobin serves to decrease the ability of iron derived from hemoglobin from carrying out oxidative reactions [7]. In man their exists two possible alleles at the Hp genetic locus, denoted 1 and 2. The protein product of the Hp 2 allele is defective in its ability to block oxidative reactions mediated by iron derived hemoglobin. Therefore, while the Hp 1-Hb complex is relatively redox inert, the Hp 2-Hb complex contains by definition nontransferrin bound redox-active iron [5].
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影响因子：
2.1
作者：
Blum S;Vardi M;Brown JB;Russell A;Milman U;Shapira C;Levy NS;Miller-Lotan R;Asleh R;Levy AP
通讯作者：
Levy AP
触珠蛋白 2-2 基因型与动脉粥样硬化斑块中氧化还原活性血红蛋白衍生铁的增加有关。
影响因子：
5.3
作者：
Kalet-Litman,Shiri;Moreno,PedroR;Levy,AndrewP
通讯作者：
Levy,AndrewP
DOI：
10.1016/s0955-3886(00)00087-4
发表时间：
2000-12-01
期刊：
TRANSFUSION SCIENCE
影响因子：
--
作者：
Breuer, W;Hershko, C;Cabantchik, ZI
通讯作者：
Cabantchik, ZI
结合珠蛋白基因型在治疗 HDL 功能障碍中的药物基因组学应用
影响因子：
1.9
作者：
Avery Schwartz;S. Blum;R. Asleh;M. Pollak;Shiri Kalet;A. Levy
通讯作者：
A. Levy
DOI：
10.1016/s0735-1097(02)02534-2
发表时间：
2002-12-04
影响因子：
24
作者：
Levy, AP;Hochberg, I;Howard, BV
通讯作者：
Howard, BV