Orem Cihan, Orem Asim, Uydu Hüseyin Avni, Celik Sükrü, Erdöl Cevdet, Kural Birgül Vanizor
Department of Cardiology, Karadeniz Technical University, Trabzon, Turkey.
Coron Artery Dis. 2002 Feb;13(1):65-71. doi: 10.1097/00019501-200202000-00009.
Oxidized low-density lipoprotein (Ox-LDL) is believed to play an important role in the progression of atherosclerosis. Oxidative modification of low-density lipoprotein (LDL) is a prerequisite for rapid accumulation of LDL in macrophages and for the formation of foam cells. Because of high antioxidant levels in plasma, LDL oxidation is suggested to occur mainly in the subendothelial space of the arterial wall, where there is the concomitant presence of large amounts of reactive oxygen species generated by endothelial cells and activated leukocytes. After Ox-LDL formation, antibodies against this form of LDL may occur. Auto-antibodies against Ox-LDL (AuAb-Ox-LDL) show directly in in-vivo LDL oxidation. Many studies have indicated that the amount of antibodies in serum is positively correlated to the rate of progression of atherosclerotic plaques.
In this study the effect of lipid-lowering therapy on the levels of AuAb-Ox-LDL in patients with dyslipidemia was determined using atorvastatin (10 mg/day), and the relationship between the antibodies and plasma total antioxidant status (TAS) and LDL oxidation capacity was also investigated. Serum levels of AuAb-Ox-LDL, lipids, lipoproteins, TAS and susceptibility of LDL to oxidation were determined using lag time in 44 patients with dyslipidemia (29 with hypercholesterolemia and 15 with mixed-type hyperlipidemia).
After lipid-lowering therapy, serum levels of AuAb-Ox-LDL were found to be significantly decreased, by 18.7%, while lag time and plasma TAS were increased (31.3% and 7.6% respectively) in patients with dyslipidemia. The percentage change in lag time was found to be negatively correlated to the percentage change in AuAb-Ox-LDL (r = -0.31, P < 0.05). The percentage change in lag time also showed a positive correlation with the percentage change in TAS (r = 0.58, P < 0.01). AuAb-Ox-LDL levels decreased by 21.7% in patients with hypercholesterolemia and by 12.6% in patients with mixed-type hyperlipidemia. Also AuAb-Ox-LDL levels in patients with hypercholesterolemia were higher than in those with mixed-type hyperlipidemia (367 +/- 294 compared with 300 +/- 176 mU/l).
It was concluded that lipid-lowering therapy may contribute to the reduction in levels of AuAb-Ox-LDL and the increase in the antioxidant capacity of plasma LDL and TAS. It was also suggested that the measurement of antibodies against Ox-LDL during lipid-lowering therapy may be used as an important marker for representing in-vivo LDL oxidation and atherosclerotic processes.
氧化型低密度脂蛋白（Ox-LDL）被认为在动脉粥样硬化的进展中起重要作用。低密度脂蛋白（LDL）的氧化修饰是LDL在巨噬细胞中快速积聚以及形成泡沫细胞的前提条件。由于血浆中抗氧化剂水平较高，LDL氧化被认为主要发生在动脉壁的内皮下间隙，此处同时存在大量由内皮细胞和活化白细胞产生的活性氧。Ox-LDL形成后，可能会出现针对这种形式LDL的抗体。抗Ox-LDL自身抗体（AuAb-Ox-LDL）直接显示体内LDL的氧化情况。许多研究表明，血清中抗体的量与动脉粥样硬化斑块的进展速率呈正相关。
在本研究中，使用阿托伐他汀（10毫克/天）确定降脂治疗对血脂异常患者中AuAb-Ox-LDL水平的影响，并研究抗体与血浆总抗氧化状态（TAS）和LDL氧化能力之间的关系。采用滞后时间测定44例血脂异常患者（29例高胆固醇血症患者和15例混合型高脂血症患者）的血清AuAb-Ox-LDL、血脂、脂蛋白、TAS水平以及LDL的氧化敏感性。
降脂治疗后，血脂异常患者血清中AuAb-Ox-LDL水平显著降低，降幅为18.7%，而滞后时间和血浆TAS升高（分别升高31.3%和7.6%）。发现滞后时间的百分比变化与AuAb-Ox-LDL的百分比变化呈负相关（r = -0.31，P < 0.05）。滞后时间的百分比变化也与TAS的百分比变化呈正相关（r = 0.58，P < 0.01）。高胆固醇血症患者的AuAb-Ox-LDL水平降低21.7%，混合型高脂血症患者降低12.6%。此外，高胆固醇血症患者的AuAb-Ox-LDL水平高于混合型高脂血症患者（分别为367±294与300±176 mU/l）。
得出的结论是，降脂治疗可能有助于降低AuAb-Ox-LDL水平，并提高血浆LDL和TAS的抗氧化能力。还表明，在降脂治疗期间检测抗Ox-LDL抗体可作为代表体内LDL氧化和动脉粥样硬化进程的重要标志物。
