Asselin Caroline, Ducharme Anique, Ntimbane Thierry, Ruiz Matthieu, Fortier Annik, Guertin Marie-Claude, Lavoie Joël, Diaz Ariel, Levy Emile, Tardif Jean-Claude, Des Rosiers Christine
Montreal Heart Institute, Research Center, 5000 Belanger Street, Montreal, Quebec, Canada H1T 1C8.
Department of Medicine, Université de Montréal, Montreal, Quebec, Canada ; Montreal Heart Institute, Research Center, 5000 Belanger Street, Montreal, Quebec, Canada H1T 1C8.
Redox Biol. 2013 Dec 18;2:148-55. doi: 10.1016/j.redox.2013.12.009. eCollection 2014.
Measurements of oxidative stress biomarkers in patients with heart failure (HF) have yielded controversial results. This study aimed at testing the hypothesis that circulating levels of the lipid peroxidation product 4-hydroxynonenal bound to thiol proteins (4HNE-P) are strongly associated with those of its potential precursors, namely n-6 polyunsaturated fatty acids (PUFA).
Circulating levels of 4HNE-P were evaluated by gas chromatography-mass spectrometry in 71 control subjects and 61 ambulatory symptomatic HF patients along with various other clinically- and biochemically-relevant parameters, including other oxidative stress markers, and total levels of fatty acids from all classes, which reflect both free and bound to cholesterol, phospholipids and triglycerides. All HF patients had severe systolic functional impairment despite receiving optimal evidence-based therapies. Compared to controls, HF patients displayed markedly lower circulating levels of HDL- and LDL-cholesterol, which are major PUFA carriers, as well as of PUFA of the n-6 series, specifically linoleic acid (LA; P=0.001). Circulating 4HNE-P in HF patients was similar to controls, albeit multiple regression analysis revealed that LA was the only factor that was significantly associated with circulating 4HNE-P in the entire population (R (2)=0.086; P=0.02). In HF patients only, 4HNE-P was even more strongly associated with LA (P=0.003) and HDL-cholesterol (p<0.0002). Our results demonstrate that 4HNE-P levels, expressed relative to HDL-cholesterol, increase as HDL-cholesterol plasma levels decrease in the HF group only.
Results from this study emphasize the importance of considering changes in lipids and lipoproteins in the interpretation of measurements of lipid peroxidation products. Further studies appear warranted to explore the possibility that HDL-cholesterol particles may be a carrier of 4HNE adducts.
对心力衰竭（HF）患者氧化应激生物标志物的测量结果存在争议。本研究旨在验证脂质过氧化产物4-羟基壬烯醛与硫醇蛋白结合物（4HNE-P）的循环水平与其潜在前体即n-6多不饱和脂肪酸（PUFA）的循环水平密切相关这一假设。
采用气相色谱-质谱法评估了71名对照受试者和61名症状性门诊HF患者的4HNE-P循环水平，同时还检测了各种其他临床和生化相关参数，包括其他氧化应激标志物以及各类脂肪酸的总水平，后者反映了游离脂肪酸以及与胆固醇、磷脂和甘油三酯结合的脂肪酸水平。所有HF患者尽管接受了基于最佳证据的治疗，但仍存在严重的收缩功能障碍。与对照组相比，HF患者中作为主要PUFA载体的高密度脂蛋白胆固醇（HDL-胆固醇）和低密度脂蛋白胆固醇的循环水平显著降低，n-6系列PUFA的循环水平也显著降低，尤其是亚油酸（LA；P=0.001）。HF患者的循环4HNE-P水平与对照组相似，尽管多元回归分析显示LA是整个人群中与循环4HNE-P显著相关的唯一因素（R²=0.086；P=0.02）。仅在HF患者中，4HNE-P与LA（P=0.003）和HDL-胆固醇（P<0.0002）的相关性更强。我们的结果表明，仅在HF组中，相对于HDL-胆固醇而言，4HNE-P水平会随着血浆HDL-胆固醇水平的降低而升高。
本研究结果强调了在解释脂质过氧化产物测量结果时考虑脂质和脂蛋白变化的重要性。有必要进一步开展研究，以探索HDL-胆固醇颗粒可能是4HNE加合物载体的可能性。
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