HEMIN - A POSSIBLE PHYSIOLOGICAL MEDIATOR OF LOW-DENSITY-LIPOPROTEIN OXIDATION AND ENDOTHELIAL INJURY
HEMIN - A POSSIBLE PHYSIOLOGICAL MEDIATOR OF LOW-DENSITY-LIPOPROTEIN OXIDATION AND ENDOTHELIAL INJURY
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DOI：
10.1161/01.atv.11.6.1700
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发表时间：
1991-11-01
期刊：
影响因子：
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通讯作者：
VERCELLOTTI, GM
中科院分区：
文献类型：
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作者：
BALLA, G;JACOB, HS;VERCELLOTTI, GM
氧化低密度脂蛋白（LDL），在体内形成的目前未知的反应，可能在动脉粥样硬化形成中发挥作用。 在体外，过渡金属如铁和铜将促进LDL氧化，但这些金属不太可能以游离形式存在于正常体液中。 我们已经探讨了血红素促进LDL氧化的可能性，血红素是一种生理上普遍存在的疏水性含铁化合物。 事实上，在几个小时的孵育过程中，血红素引起广泛的氧化修饰的LDL;然而，这种修改只需要几分钟的存在下，少量的过氧化氢或预形成的脂质过氧化氢的LDL。 血红素、LDL和过氧化物之间的氧化相互作用导致血红素环的降解和随后的血红素铁的释放，这进一步加速血红素降解。 耦合（明显铁催化）血红素降解和LDL氧化都有效地抑制疏水性抗氧化剂和铁螯合剂。 这种氯化血红素诱导的LDL氧化可能参与动脉粥样硬化形成，这一发现支持氯化血红素氧化的LDL对培养的主动脉内皮细胞具有极强的细胞毒性。 总的来说，这些研究不仅支持这样的想法，即LDL氧化的生理物质，如血红素可能在动脉粥样硬化的过程中发挥作用，但也可能有更广泛的影响，血红素和不饱和脂肪酸之间的类似的氧化反应可能会发生出血性损伤。
Oxidized low density lipoprotein (LDL), formed in vivo from presently unknown reactions, may play a role in atherogenesis. In vitro, transition metals such as iron and copper will facilitate LDL oxidation, but these metals are unlikely to exist in free form in normal body fluids. We have explored the possibility that LDL oxidation may be promoted by heme, a physiologically ubiquitous, hydrophobic, iron-containing compound. Indeed, during several-hour incubation, heme caused extensive oxidative modification of LDL; however, such modification requires only minutes in the presence of small amounts of H2O2 or preformed lipid hydroperoxides within the LDL. Oxidative interactions between heme, LDL, and peroxides lead to degradation of the heme ring and consequent release of heme iron, which further accelerates heme degradation. Coupled (evidently iron-catalyzed) heme degradation and LDL oxidation are both effectively inhibited by hydrophobic antioxidants and iron chelators. That such hemin-induced LDL oxidation may be involved in atherogenesis is supported by the finding that LDL oxidized by hemin is extremely cytotoxic to cultured aortic endothelial cells. Overall, these investigations not only lend support to the idea that LDL oxidation by physiological substances such as heme may play a role in the process of atherogenesis but also may have broader implications, as similar oxidative reactions between heme and unsaturated fatty acids may occur consequent to hemorrhagic injury.