HIGH-DENSITY-LIPOPROTEIN INHIBITS THE OXIDATIVE MODIFICATION OF LOW-DENSITY-LIPOPROTEIN
HIGH-DENSITY-LIPOPROTEIN INHIBITS THE OXIDATIVE MODIFICATION OF LOW-DENSITY-LIPOPROTEIN
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DOI：
10.1016/0005-2760(90)90314-n
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发表时间：
1990-05-22
期刊：
影响因子：
--
通讯作者：
FONG, LG
中科院分区：
文献类型：
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作者：
PARTHASARATHY, S;BARNETT, J;FONG, LG
氧化修饰的低密度脂蛋白（LDL），由LDL与特定细胞（例如，内皮细胞，EC）或氧化还原金属如铜，已经被认为是LDL的致动脉粥样硬化形式。流行病学证据表明，较高浓度的血浆高密度脂蛋白（HDL）可预防该疾病。在本研究中描述了HDL对氧化修饰的LDL产生的影响。孵育的HDL与内皮细胞，或与铜，产生低得多的量的硫代巴比妥酸反应产物（TBARS）相比，孵育含有LDL在相同的蛋白质浓度。与类似孵育的LDL相比，这种孵育也没有导致孵育的HDL巨噬细胞的降解增强。另一方面，在含有标记LDL的孵育物中加入HDL对巨噬细胞随后降解孵育的LDL具有显著的抑制作用，而对TBARS的产生或共轭二烯的形成没有影响。这种抑制不是由于HDL的改变，如以下发现所示。(A)有没有增强的巨噬细胞降解的HDL与EC或铜单独孵育，连同LDL，尽管TBARS的产生增加。(B)赖氨酸基团被阻断的HDL（乙酰HDL、丙二醛（MDA）HDL）仍然能够阻止LDL的修饰，并且（C）乙酰HDL和MDA-HDL对氧化修饰的LDL的降解竞争很差。这表明，高密度脂蛋白可以发挥保护作用，在动脉粥样硬化形成，防止氧化修饰的低密度脂蛋白的产生。HDL的作用机制可能涉及脂蛋白之间脂质过氧化产物的交换。
Oxidatively modified low-density lipoprotein (LDL), generated as a result of incubation of LDL with specific cells (e.g., endothelial cells, EC) or redox metals like copper, has been suggested to be an atherogenic form of LDL. Epidemiological evidence suggests that higher concentrations of plasma high-density lipoprotein (HDL) are protective against the disease. The effect of HDL of the generation of the oxidatively modified LDL is described in the current study. Incubation of HDL with endothelial cells, or with copper, produced much lower amounts of thiobarbvituric acid-reactive products (TBARS) as compared to incubations that contained LDL at equal protein concentrations. Such incubations also did not result in an enhanced degradation of the incubated HDL buy macrophages in contrast to similarly incubated LDL. On the other hand, inclusion of HDL in the incubations that contained labeled LDL had a profound inhibitory effect on the subsequent degradation of the incubated LDL by the macrophages while having no effect on the generation of TBARS or the formation of conjugated dienes. This inhibition was not due to the modification of HDL as suggested by the following findings. (A) There was no enhanced macrophage degradation of the HDL incubated with EC or copper alone, together with LDL, despite an increased generation of TBARS. (B) HDL with the lysine groups blocked (acetyl HDL, malondialdehyde (MDA) HDL) was still able to prevent the modification of LDL and (C) acetyl HDL and MDA-HDL competed poorly for the degradation of oxidatively modified LDL. It is suggested that HDL may play a protective role in atherogenesis by preventing the generation of an oxidatively modified LDL. The mechanism of action of HDL may involve exchange of lipid peroxidation products between the lipoproteins.