Sutherland Wayne H, Williams Michael J, de Jong Sylvia A
Department of Medical and Surgical Sciences, University of Otago, Dunedin, New Zealand.
Arch Med Res. 2007 Oct;38(7):757-63. doi: 10.1016/j.arcmed.2007.04.004. Epub 2007 Jun 21.
Lipid oxidation products react with protein to produce lipofuscin-like fluorophores (P-LLF) and modified apolipoprotein B that is an important element of the atherogenic properties of oxidized low-density lipoprotein (oxLDL). The aim of this study was to compare plasma concentrations of P-LLF between men with coronary artery disease (CAD) treated with statin drugs and healthy controls and to identify determinants of P-LLF.
Plasma markers of protein modification including P-LLF and oxidized low-density lipoprotein-4E6 (oxLDL-4E6), low-density lipoprotein-conjugated dienes (LDL-CD), lipid peroxides, apolipoprotein B, and serum albumin were measured in 24 men with CAD who were receiving statin therapy and 20 healthy men in the same age range.
Plasma P-LLF (+23%, p = 0.001) was significantly higher and plasma oxLDL-4E6 (-33%, p <0.001) and apolipoprotein B (apoB) (-30%, p <0.001) concentrations were significantly lower in men with CAD compared with controls. Plasma P-LLF concentration was correlated significantly with plasma apoB (r = -0.596, p <0.001), serum albumin (r = 0.518, p <0.001), and age (r = 0.390, p = 0.009) and these variables were independent predictors of P-LLF in the study population. Plasma P-LLF was no longer significantly higher in men with CAD when plasma apoB concentration was taken into account.
Plasma P-LLF concentration is abnormally high and appears to be closely associated with lower levels of apoB in men with CAD receiving statin therapy. ApoB may be a preferential target of reactive aldehydic lipid oxidation products and a decrease in apoB may increase the quantity of these products available for condensation with albumin.
脂质氧化产物与蛋白质反应生成脂褐素样荧光团(P-LLF)以及修饰的载脂蛋白B,后者是氧化型低密度脂蛋白(oxLDL)致动脉粥样硬化特性的重要成分。本研究旨在比较接受他汀类药物治疗的冠心病(CAD)男性患者与健康对照者血浆中P-LLF的浓度,并确定P-LLF的决定因素。
对24例接受他汀治疗的CAD男性患者和20例年龄范围相同的健康男性,测定血浆中蛋白质修饰标志物,包括P-LLF、氧化型低密度脂蛋白-4E6(oxLDL-4E6)、低密度脂蛋白共轭二烯(LDL-CD)、脂质过氧化物、载脂蛋白B和血清白蛋白。
与对照组相比,CAD男性患者血浆P-LLF浓度显著升高(+23%,p = 0.001),而血浆oxLDL-4E6(-33%,p <0.001)和载脂蛋白B(apoB)浓度显著降低(-30%,p <0.001)。血浆P-LLF浓度与血浆apoB(r = -0.596,p <0.001)、血清白蛋白(r = 0.518,p <0.001)和年龄(r = 0.390,p = 0.009)显著相关,这些变量是研究人群中P-LLF的独立预测因子。当考虑血浆apoB浓度时,CAD男性患者血浆P-LLF不再显著升高。
接受他汀治疗的CAD男性患者血浆P-LLF浓度异常升高,且似乎与较低的apoB水平密切相关。ApoB可能是活性醛类脂质氧化产物的优先靶点,apoB的减少可能会增加这些产物与白蛋白缩合的量。