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氧化型低密度脂蛋白作为心血管疾病的生物标志物。

Oxidized low-density lipoprotein as a biomarker of cardiovascular diseases.

机构信息

Laboratory of Radiobiology and Molecular Genetics, Vinca Institute of Nuclear Sciences, University of Belgrade , Belgrade , Serbia .

出版信息

Crit Rev Clin Lab Sci. 2015;52(2):70-85. doi: 10.3109/10408363.2014.992063. Epub 2014 Dec 24.

Abstract

Atherosclerosis is a life-long illness that begins with risk factors, which in turn contribute to the development of subclinical disease, followed by the establishment of overt cardiovascular disease (CVD). Thrombotic-occlusive complications of atherosclerosis are among the most widespread and costly health problems. Oxidized low-density lipoprotein (OxLDL) plays an important role in atherogenesis by promoting an inflammatory environment and lipid deposition in the arterial wall. As cardiovascular events occur in individuals without common risk factors, there is a need for additional tools that may help in CVD risk assessment and management. The use of biomarkers has improved diagnostic, therapeutic and prognostic outcome in cardiovascular medicine. This review elaborates on the value of circulating OxLDL as a biomarker of CVD. Three enzyme-linked immunosorbent assays (4E6, DLH3 and E06) using murine monoclonal antibodies for determination of OxLDL blood levels have been developed. However, none of these assays are currently approved for routine clinical practice. We identified studies investigating OxLDL in CVD (measured by 4E6, DLH3 or E06 assay) by searching the PubMed database. Circulating OxLDL was found to be associated with all stages of atherosclerosis, from early atherogenesis to hypertension, coronary and peripheral arterial disease, acute coronary syndromes and ischemic cerebral infarction. The results of studies investigating the usefulness of OxLDL for CVD prediction were also summarized. Furthermore, OxLDL was found to be associated with pathologic conditions linked to CVD, including diabetes mellitus, obesity and metabolic syndrome (MetS). In addition, we have addressed the mechanisms by which OxLDL promotes atherogenesis, and the effects of antiatherogenic treatments on circulating OxLDL. Finally, we highlight the evidence suggesting that lipoprotein (a) [Lp(a)] is the preferential carrier of oxidized phospholipids (OxPL) in human plasma. A strong association between OxPL/apoB level (representing the content of OxPL on apolipoprotein B-100 particles, measured by E06 assay) and Lp(a) has been determined.

摘要

动脉粥样硬化是一种终身疾病,始于危险因素,这些危险因素反过来又导致亚临床疾病的发展,随后导致明显的心血管疾病(CVD)。动脉粥样硬化的血栓闭塞性并发症是最广泛和最昂贵的健康问题之一。氧化低密度脂蛋白(OxLDL)通过促进动脉壁中的炎症环境和脂质沉积,在动脉粥样硬化形成中起重要作用。由于心血管事件发生在没有常见危险因素的个体中,因此需要其他工具来帮助评估和管理 CVD 风险。生物标志物的使用改善了心血管医学的诊断、治疗和预后结果。本综述阐述了循环 OxLDL 作为 CVD 标志物的价值。已经开发了三种使用针对 OxLDL 的鼠单克隆抗体测定血液水平的酶联免疫吸附测定法(4E6、DLH3 和 E06)。然而,目前没有一种检测方法被批准用于常规临床实践。我们通过搜索 PubMed 数据库,确定了研究 OxLDL 在 CVD 中的作用(通过 4E6、DLH3 或 E06 检测)的研究。研究发现,循环 OxLDL 与动脉粥样硬化的所有阶段有关,从早期动脉粥样硬化到高血压、冠状动脉和外周动脉疾病、急性冠状动脉综合征和缺血性脑梗死。还总结了研究 OxLDL 对 CVD 预测有用性的研究结果。此外,还发现 OxLDL 与与 CVD 相关的病理状况有关,包括糖尿病、肥胖和代谢综合征(MetS)。此外,我们还探讨了 OxLDL 促进动脉粥样硬化形成的机制,以及抗动脉粥样硬化治疗对循环 OxLDL 的影响。最后,我们强调了提示脂蛋白(a)[Lp(a)]是人类血浆中氧化磷脂(OxPL)的首选载体的证据。已经确定了 OxPL/apoB 水平(通过 E06 检测代表载脂蛋白 B-100 颗粒上 OxPL 的含量)与 Lp(a)之间的强相关性。

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