McCall M R, Tang J Y, Bielicki J K, Forte T M
Department of Molecular and Nuclear Medicine, Lawrence Berkeley Laboratory, University of California at Berkeley 94720, USA.
Arterioscler Thromb Vasc Biol. 1995 Oct;15(10):1599-606. doi: 10.1161/01.atv.15.10.1599.
Experimental evidence suggests that aldehydes generated as a consequence of lipid peroxidation may be involved in the pathogenesis of atherosclerosis. It is well documented that aldehydes modify LDL: however, less is known concerning the effects of aldehydes on other plasma and interstitial fluid components. In the present study, we investigated the effects of five physiologically relevant aldehydes (acetaldehyde, acrolein, hexanal, 4-hydroxynonenal [HNE], and malondialdehyde [MDA]) on two key constituents of the antiatherogenic reverse cholesterol transport pathway, lecithin-cholesterol acyltransferase (LCAT) and HDL. Human plasma was incubated for 3 hours at 37 degrees C with each one of the five aldehydes at concentrations ranging from 0.16 to 84 mmol/L. Dose-dependent decreases in LCAT activity were observed. The short-chain (acrolein) and long-chain (HNE) alpha,beta-unsaturated aldehydes were the most effective LCAT inhibitors. Micromolar concentrations of these unsaturated aldehydes resulted in significant reductions in plasma LCAT activity. The short- and longer-chain saturated aldehydes acetaldehyde and hexanal and the dialdehyde MDA were considerably less effective at inhibiting LCAT than were acrolein and HNE. In addition to inhibiting LCAT, aldehydes increased HDL electrophoretic mobility and cross-linked HDL apolipoproteins. Cross-linking of apolipoproteins A-I and A-II required higher aldehyde concentrations than inhibition of LCAT. The alpha,beta-unsaturated aldehydes acrolein and HNE were fourfold to eightfold more effective cross-linkers of apolipoproteins A-I and A-II than the other aldehydes studied. These data suggest that products of lipid peroxidation, especially unsaturated aldehydes, may interfere with normal HDL cholesterol transport by inhibiting LCAT and modifying HDL apolipoproteins.
实验证据表明，脂质过氧化产生的醛类可能参与动脉粥样硬化的发病机制。醛类修饰低密度脂蛋白（LDL）已有充分记录；然而，关于醛类对其他血浆和组织液成分的影响，人们了解较少。在本研究中，我们研究了五种生理相关醛类（乙醛、丙烯醛、己醛、4-羟基壬烯醛 [HNE] 和丙二醛 [MDA]）对抗动脉粥样硬化逆向胆固醇转运途径的两个关键成分，即卵磷脂胆固醇酰基转移酶（LCAT）和高密度脂蛋白（HDL）的影响。将人血浆在37℃下与五种醛类中的每一种在浓度范围为0.16至84 mmol/L下孵育3小时。观察到LCAT活性呈剂量依赖性降低。短链（丙烯醛）和长链（HNE）α,β-不饱和醛是最有效的LCAT抑制剂。这些不饱和醛的微摩尔浓度导致血浆LCAT活性显著降低。短链和长链饱和醛乙醛和己醛以及二醛MDA在抑制LCAT方面比丙烯醛和HNE的效果要差得多。除了抑制LCAT外，醛类还增加了HDL的电泳迁移率并使HDL载脂蛋白发生交联。载脂蛋白A-I和A-II的交联所需的醛浓度高于抑制LCAT所需的浓度。α,β-不饱和醛丙烯醛和HNE作为载脂蛋白A-I和A-II的交联剂，其效果是所研究的其他醛类的四至八倍。这些数据表明，脂质过氧化产物，尤其是不饱和醛类，可能通过抑制LCAT和修饰HDL载脂蛋白来干扰正常的HDL胆固醇转运。
