Prevention of Restenosis after Coronary Angioplasty with Low-Density Lipoprotein Apheresis

Abstract: A prospective study was performed to determine whether low-density lipoprotein (LDL) apheresis, when performed only immediately before and after percutaneous transluminal coronary angioplasty (PTCA), is effective in preventing restenosis of coronary artery lesions following PTCA. Thirty-six patients with coronary heart disease (CHD) and hypercholesterolemia were divided into 2 groups. The 9 patients in the LDL group underwent LDL-apheresis 1 day before and 5 days after PTCA while the 27 patients of the control group underwent PTCA but did not undergo LDL-apheresis. Follow-up coronary angiography (CAG) was performed 4 months after PTCA. The rate of restenosis of coronary artery lesions was significantly lower in the LDL group (0%) than in the control group (30%). These findings suggest that LDL-apheresis, when performed before and after PTCA, is effective in preventing restenosis of coronary artery lesions in patients with CHD and hypercholesterolemia.     

两种清除法测定低密度脂蛋白胆固醇的临床评价

目的对表面活性剂清除法 (SUR法 )和过氧化氢酶清除法 (CAT法 )两种低密度脂蛋白胆固醇 (LDL C)均相测定法进行临床评价。方法将上述两种方法与聚乙烯硫酸沉淀法 (PVS法 )进行比较 ,分析各自方法的精密度、准确性、特异性和干扰因素。结果两种清除法与PVS法 (X)具有良好的相关性 ,SUR法 (Y1) :Y1=0 .9311X +0 .10 2 2 ,r =0 .980 1;CAT法 (Y2 ) :Y2 =0 .94 0 1X +0 .0 991,r=0 .9832。高、中、低三种LDL C浓度混合血清所测定结果表明两种方法均具有良好的精密度 ,总CV值SUR法 3.4 5 - 3.89% ,CAT法 3.5 1- 3.99% ,均达到临床满意的程度。两法线性范围均较宽 (线性均至 8.2 2mmol/L) ,最低检测浓度均为 0 .12mmol/L ,平均回收率SUR法为 98.0 % ,CAT法为 97.6 %。TG <14 .2mmol/L ,Hb <5g/L ,HDL C <3.88mmol/L ,胆红素 <4 5 0 μmol/L对两法基本无影响。 结论两种LDL C清除法测定结果的准确度和精密度均符合临床要求 ,适宜自动分析 ,值得在临床推广应用。     

冠心病病人氧化修饰低密度脂蛋白的测定及临床意义

目的 :探讨氧化修饰低密度脂蛋白 (Ox LDL)对冠心病 (CHD)形成和发展的影响。方法 :CHD组 6 0例 ,对照组 5 3例。用酶标多克隆抗体夹心的方法检测血清Ox LDL含量。结果 :CHD组血清Ox LDL含量为 ( 48.6± 32 .8) μg dl。对照组( 2 5 .9± 2 2 .5 ) μg dl,两组之间Ox LDL含量存在显著性差异 (P <0 .0 0 1)。 结论 :Ox LDL和CHD有密切的关系 ,故可作为CHD病人特异性的辅助诊断指标。     

Comparison of iodine-123 low-density lipoprotein (LDL) and indium-111 LDL binding to mononuclear cells of healthy normolipaemic controls and patients with heterozygous familial hypercholesterolaemia

The binding of radiolabelled lipoproteins, iodine-123-labelled low-density. lipoprotein (LDL) and indium-111-labelled LDL, to peripheral blood mononuclear cells (MNCs) was compared in normolipaemic subjects and in patients with heterozygous familial hypercholesterolaemia (FH). ¹²³I-LDL and ¹¹¹In-LDL binding to MNCs exhibited high-affinity, highly specific, time- and temperature-dependent binding reaching saturation at concentrations above 50 nM. The number of LDL binding sites (B_max) was significantly (P<0.01) lower in FH patients (P<0.001; ¹²³I-LDL: B_max 279±44 ng protein/10⁸MNCs; ¹¹¹In-LDL: B_max 309±43 ng protein/10⁸MNCs) as compared with controls (¹²³I-LDL: B_max 2874±246 ng protein/10⁸ MNCs; ¹¹¹In-LDL: B_max 3145±339 ng protein/10⁸ MNCs). The corresponding dissociation constants (K _d) were 16±8 nM for ¹²³I-LDL and 12±6 nM for ¹²³In-LDL in healthy volunteers (¹²³In-LDL vs ¹¹¹In-LDL, P<0.05). In FH patients, the K _d values were 20±8 nM for ¹²³I-LDL and 16±6 nM for ¹²³In-LDL (P<0.05 vs controls for both ¹²³I-LDL and ¹¹¹In-LDL). ¹¹¹In-LDL binding to MNCs was inhibited (IC₅₀) by 30±8 nM in healthy controls and 38±12 nM in FH patients (P<0.05). ¹²³In-LDL binding to MNCs was inhibited (IC₅₀) by 34±8 nM in healthy controls and 46±10 nM in FH patients (P<0.05). Taken together, these results suggest a reduced number of LDL receptors expressed on MNCs from FH patients. We conclude that ¹¹¹In-LDL and ¹²³I-LDL are equally well suited as a probe of receptor-mediated binding and uptake of LDL.     

Antioxidant enzymes and paraoxonase show a co-activity in preserving low-density lipoprotein from oxidation

Oxidative modification of low-density lipoprotein in the artery wall plays a crucial role in the development of atherosclerosis. This physiopathological mechanism is clearly inhibited by high-density lipoprotein possibly via paraoxonase enzyme activity, present in high-density lipoprotein. In this study we determined the in vitro susceptibility of low-density lipoprotein to oxidation and the effect of various factors, such as paraoxonase phenotypes, on this process. Low-density lipoprotein from healthy volunteers (n=66) was isolated using the precipitant reagent and the oxidation was evaluated by measuring the malonyl dialdehyde and diene levels. Low-density lipoprotein cholesterol and phospholipid, vitamin E, serum cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol levels, and erythrocyte antioxidant enzymes were also determined. There was no difference among the parameters with regard to gender. Low-density lipoprotein samples obtained from subjects with the AA allele were more prone to oxidation, as observed by their higher stimulated conjugated diene (P=0.041) and thiobarbituric acid-related substance (P=0.042) levels, than samples from subjects with AB or BB alleles. The subjects with the BB allele had higher superoxide dismutase (P=0.021) and catalase (insignificant increase) activities, while their conjugated diene (P=0.000) levels were lower. In conclusion, our results revealed that the high low-density lipoprotein oxidation is related to the high low-density lipoprotein cholesterol content and low phospholipid content. The present study demonstrated an increase in superoxide dismutase and catalase activities, asl well as PON1 activities, in subjects with the BB allele. Since these enzymes all show activity against low-density lipoprotein oxidation, we propose that future investigations on atherosclerotic processes should address PON1 polymorphism as well as PON1 and other antioxidant enzymes. Received: 7 May 2001 / Accepted: 14 December 2001     

Effects of estrogen on susceptibility to oxidation of low-density and high-density lipoprotein in postmenopausal women

Objective: To investigate the effects of estrogen on the susceptibility to oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in postmenopausal women. Methods: A total of 23 postmenopausal women were treated with 0.625 mg of conjugated equine estrogen daily for 3 months. Blood samples were obtained before and after therapy. Plasma levels of total cholesterol and triglyceride and the concentrations of cholesterol, triglyceride, phospholipid in LDL and HDL were determined enzymatically and the levels of apolipoprotein A-I, A-II in HDL and apolipoprotein B in LDL were measured by turbidimetric immunoassay. The isolated LDL and HDL were incubated at 37°C for 24 h with CuSO₄ 5 μmol/l and the lipid peroxide concentration of LDL and HDL was measured. Results: Estrogen significantly reduced the plasma level of total cholesterol and significantly increased the plasma level of triglyceride. The LDL concentrations of cholesterol, phospholipid and apolipoprotein B were significantly decreased following estrogen therapy. The triglyceride level of LDL did not change significantly. The HDL concentrations of cholesterol, triglyceride, phospholipid and apolipoprotein A-I and A-II were all significantly elevated after estrogen therapy. Estrogen significantly inhibited the peroxidation of LDL at 50–2000 μg of LDL protein (14.17±4.17–11.49±1.42 nmol/200 μg of LDL protein, P<0.001) and of HDL (4.49±1.74–3.37±1.24 nmol/200 μg of HDL protein, P<0.03) induced by their incubation in the presence of CuSO₄. Conclusions: Estrogen inhibited the susceptibility of LDL and HDL to oxidative modification and favorably affected lipid metabolism by reducing the number of LDL particles and increasing the number of HDL particles in plasma that were resistant to oxidation.     

雌激素对氧化型低密度脂蛋白诱导的血管内皮细胞凋亡的影响

目的：观察雌激素（１７β－雌二醇）对氧化型低密度脂蛋白（ｏｘＬＤＬ）诱导人脐静脉内皮细胞（ＨＵＶＥＣ）凋亡的影响。方法 以ＨＵＶＥＣ为对象,观察不同浓度的１７β－雌二醇（１,１０和１００μｍｏｌ／Ｌ）对ｏｘＬＤＬ（４μｇ／Ｌ）诱导的凋亡的影响。结果 不同剂量的１７β－雌二醇对使用ｏｘＬＤＬ诱导的ＨＵＶＥＣ凋亡减少７０％￣９３％,其抑制呈明显的正向量效应关系,１７β－雌二醇１μｍｏｌ／Ｌ组细胞凋亡占     

The Effect of Gastric Bypass on Cholesterol,HDL, and the Risk of Coronary Heart Disease

A review of 150 charts revealed that 36 patients had pre-operative serum cholesterol greater than 200 mg% prior to Roux-Y gastric bypass. The average pre-operative weight was 266 lb (121 kg) and at 1 year post-operative 166 lb (75 kg), or 100 lb (45 kg) lost (77% excess weight loss). We compared the following pre- and post- operative data and found that: (1) cholesterol was decreased by 24% and triglycerides decreased by 40%; (2) post-operative cholesterol/HDL-C ratio of 3.31 put our patients in the half of average risk category for a clinical pathological coronary event according to the SmithKline Beecham Laboratories risk ratio chart. We conclude that Roux-Y gastric bypass and its ability to produce a significant weight loss and markedly affect cholesterol and triglyceride metabolism will also reduce a patient's risk of myocardial infarction.     

Particle release in extracorporeal low-density lipoprotein lowering therapies

Release of microparticles into the blood during extracorporeal circulation must be kept low because of possibly serious acute and chronic adverse effects. Concentration and size distribution of microparticles were measured during simulated treatments (n = 7) on original equipment for 2 standard low-density lipoprotein (LDL) elimination procedures (DALI 750, Fresenius AG, St. Wendel, Germany and Liposorber, Kaneka Corporation, Osaka, Japan) and compared to hemofiltration solutions. For both systems as well as in hemofiltration solutions, the mean particle concentrations in 500 ml portions gathered from the efferent blood line stayed below 10% of pharmacopoeia standards for infusion solutions (United States Pharmacopoeia, European Pharmacopoeia) in all measured size classes. Although particle concentrations were comparable in all systems, the mean total number of particles > or =2 microm released per session was lowest in the DALI (167,000) compared to the Liposorber (465,000) and hemofiltration solutions (2,240,000). This was mainly due to different total processed blood volumes necessary to achieve the required LDL reduction.