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氧化型低密度脂蛋白:已知内容与待阐明之处

Oxidized low-density lipoproteins: what is understood and what remains to be clarified.

作者信息

Itabe Hiroyuki

机构信息

Department of Molecular Pathology, Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko, Tsukui, Kanagawa 199-0195, Japan.

出版信息

Biol Pharm Bull. 2003 Jan;26(1):1-9. doi: 10.1248/bpb.26.1.

Abstract

Oxidized low-density lipoprotein (OxLDL) has previously been thought to promote atherogenesis through foam cell formation. However, the actual nature of OxLDL present in vivo remained obscure until recently. We have produced a monoclonal antibody, DLH3, which specifically binds to OxLDL but not to native LDL. The presence of OxLDL in the LDL fraction of human plasma was demonstrated by introducing a sandwich ELISA procedure using DLH3 together with an anti-apoB antibody. Furthermore, OxLDL levels appeared to increase in certain pathological conditions including acute myocardial infarction and carotid artery atherosclerosis. Accumulation of OxLDL in atherosclerotic lesions has also been demonstrated by immunohistochemical and biochemical studies using the DLH3 antibody. This antibody recognizes oxidized phosphatidylcholines (OxPC) generated during oxidative modification of LDL, and OxPC-apoB adducts formed in OxLDL are the presumed antigens. Measuring OxLDL in plasma would be a useful diagnostic tool for cardiovascular diseases. However, there still remain some major questions related to OxLDL, the answers to which are crucial for understanding the mechanisms of atherogenesis.

摘要

氧化型低密度脂蛋白(OxLDL)此前一直被认为通过泡沫细胞形成促进动脉粥样硬化的发生。然而,直到最近,体内存在的OxLDL的实际性质仍不清楚。我们制备了一种单克隆抗体DLH3,它能特异性结合OxLDL,但不与天然LDL结合。通过引入一种夹心ELISA程序,使用DLH3和抗载脂蛋白B抗体,证明了人血浆LDL部分中存在OxLDL。此外,在某些病理状况下,包括急性心肌梗死和颈动脉粥样硬化,OxLDL水平似乎会升高。使用DLH3抗体的免疫组织化学和生化研究也证明了OxLDL在动脉粥样硬化病变中的积累。该抗体识别LDL氧化修饰过程中产生的氧化磷脂酰胆碱(OxPC),并且OxLDL中形成的OxPC-载脂蛋白B加合物被认为是抗原。检测血浆中的OxLDL将是心血管疾病的一种有用诊断工具。然而,关于OxLDL仍然存在一些主要问题,其答案对于理解动脉粥样硬化的机制至关重要。

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