Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy

Laboratory measurements of plasma lipids (principally cholesterol and triglycerides) and lipoprotein lipids (principally low-density lipoprotein [LDL] and low-density lipoprotein [HDL] cholesterol) are the cornerstone of the clinical assessment and management of atherosclerotic cardiovascular disease (CVD) risk. LDL particles, and to a lesser extent very-low-density lipoprotein [VLDL] particles, cause atherosclerosis, whereas HDL particles prevent or reverse this process through reverse cholesterol transport. The overall risk for CVD depends on the balance between the "bad" LDL (and VLDL) and "good" HDL particles. Direct assessment of lipoprotein particle numbers us now possible through nuclear magnetic resonance spectroscopic analysis.     

脂蛋白肾病2例临床病理分析

目的阐明脂蛋白肾病的临床病理特点。方法回顾性分析2例脂蛋白肾病患者的临床表现,并对其肾活检组织进行光镜、免疫组化免疫荧光及超微结构观察。结果2例脂蛋白肾病患者均存在大量蛋白尿、肾病综合征,有程度不同的贫血及镜下血尿,血清总胆固醇及甘油三酯升高。B超检查双肾体积增大。镜检可见肾小球体积明显增大,毛细血管襻高度扩张,襻内可见层状改变的大小不同、多少不等的栓子。免疫组化染色证实“栓子”apoE染色( ),超微结构观察证实“栓子”内含颗粒状嗜锇酸脂质空泡。结论脂蛋白肾病属少见肾病,患者临床常表现为蛋白尿、肾病综合征,肾小球毛细血管襻内apoE染色阳性的巨大脂蛋白栓子是脂蛋白肾病特征性的形态学改变。     

Lipoprotein spectrum analysis of uremic patients maintained on chronic hemodialysis.

It is known that patients maintained on chronic hemodialysis have elevated plasma lipids. In order to establish whether the type of kidney pathology is related to a specific lipoprotein abnormality, we measured plasma lipoprotein in eight patients with glomerulonephritis, two patients with polycystic kidney disease and nine patients that had been surgically nephrectomized. The concentration and composition of plasma very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) in patients were compared to plasma lipoproteins in a control group. In all patient groups, the lipoprotein alterations appeared identical. VLDL were elevated 3 to 4 fold, LDL were decreased 15--35% and HDL were decreased 30--45% when compared to values of our control group. Since no differences in the lipoprotein spectrum were found among the patient groups, it appears that the hypertriglyceridemia of chronic uremia is due to the uremic state per se and is not related to a specific pathology of the kidney.     

Lipoprotein analysis in the evaluation of chest pain in the emergency department

Apolipoproteins were measured in a prospective blinded fashion in blood specimens from patients with chest pain in the emergency department. A definitive diagnosis for the chest pain (non-cardiac-related in 32% and angina or myocardial infarction in 68%) was available in 136 of the 162 patients originally enrolled in the study. Logistic regression and multivariate analysis failed to show any usefulness of apolipoprotein determinations in distinguishing patients with cardiac ischemia from those without it. The clinician's initial impression of the chest pain, the electrocardiogram, a history of previous angina, myocardial infarction, or peripheral atherosclerosis, and male sex were strongly associated with the final diagnosis. We conclude that, although apolipoprotein analysis has proved useful in epidemiologic studies, the most reliable indicators of ischemic pain remain the medical history, the electrocardiogram, and the clinician's overall initial impression.     

Lipoprotein receptors and atherosclerosis

Mammalian cholesterol metabolism is governed by two key features of the steroid nucleus: it is poorly soluble in plasma and it cannot be degraded in animal tissues. Cells which require the lipid import it through their cytoplasmic membranes in the form of solubilized lipid-protein complexes, and a similar export mechanism is essential in order to maintain cellular homoeostasis. The translocation is mediated by high affinity receptors which, under normal circumstances, operate in close synchrony. Changes in the nature of the lipoprotein ligand or of the cell itself may disturb this balance and lead to the pathological sterol accumulation which characterizes atherosclerotic lesions. All body tissues engage in this traffic in cholesterol but the liver is the single most important organ since it has the capacity both to synthesize large quantities of the lipid and to excrete it from the body via a variety of receptors designed to maintain peripheral sterol levels within safe limits.     

Lipoprotein composition in hypothyroidism

Sixteen patients with hypothyroidism have had their lipid status assessed before and during replacement therapy. More than 60% had hypercholesterolaemia and more than 60% had hypertriglyceridaemia. Significant reductions in plasma cholesterol, but not in plasma triglyceride, were seen during replacement therapy. A high cholesterol: triglyceride ratio was observed in VLDL and this relationship tended back to normal during treatment. This raises the possibility that in hypothyroidism, as in Type III hyperlipoproteinaemia, an abnormality in VLDL conversion to LDL is present.     

Adiponectin and Lipoprotein Particle Size

OBJECTIVE

Adiponectin has been postulated to affect lipid and insulin signal transduction pathways. We evaluated the relationships of plasma adiponectin with lipoprotein mean particle size and subclass concentrations, independent of obesity and insulin sensitivity.

RESEARCH DESIGN AND METHODS

A cross-sectional analysis of 884 young Israeli adults who participated in the population-based Jerusalem Lipid Research Clinic (LRC) study was conducted. Lipoprotein particle size was assessed using proton nuclear magnetic resonance.

RESULTS

In multivariable linear regression models that included sex, BMI, waist circumference, homeostasis model assessment of insulin resistance, and leptin, adiponectin was associated with mean LDL size (standardized regression coefficient B = 0.20; P < 0.001), VLDL size (B = −0.12; P < 0.001), and HDL size (B = 0.06; P = 0.013). Adiponectin was inversely related to large VLDL (P < 0.001) but positively to small VLDL (P = 0.02), inversely related to small LDL (P < 0.006) but positively to large LDL (P < 0.001), and positively related to large HDL (P < 0.001) subclass concentrations.

CONCLUSIONS

Adiponectin is favorably associated with lipoprotein particle size and subclass distribution independent of adiposity and insulin sensitivity.Adiponectin is a fat-derived adipocytokine (1,2) that is strongly associated with insulin sensitivity and favorable cardiovascular outcomes. Given that insulin resistance is associated with reduced adiponectin levels (3), we hypothesized that adiponectin may have a direct role in hepatic lipoprotein metabolism. Thus, the aim of this study was to evaluate the relationships of adiponectin with lipoprotein particle size, independent of the degree of obesity and insulin sensitivity, in a population-based sample of healthy young adults.     

Lipoprotein lipase gene variants and risk of coronary disease: a quantitative analysis of population-based studies

The purpose of this study is to quantify the magnitude of the association between common variants in the lipoprotein lipase gene and coronary disease, based on published population-based studies. Fourteen studies, representing 15,708 subjects, report allelic distribution for lipoprotein lipase gene variants among coronary disease patients and control subjects. Patient outcomes included clinical coronary disease events and documented coronary disease based on angiography. Allele frequencies are estimated for disease and non-disease groups within each study. A 2X2 contingency table is used to compute individual study odds ratios and 95% confidence intervals, relating the presence of the rare allele to disease status. Mantel-Haenszel-stratified analysis of each allelic variant results in a summary odds ratio and 95% confidence interval for the association between each rare allele in the lipoprotein lipase gene and coronary disease. The lipoprotein lipase D9N allele has a summary odds ratio of 1.59 (95% confidence interval 1.03–2.55), indicating a 59% increase in risk of coronary disease for carriers with this allelic variant. The lipoprotein lipase N291S allele showed no association with coronary disease (summary odds ratio 0.93, 95% confidence interval 0.73–1.19). The summary odds ratio for lipoprotein lipase S447Ter allele is 0.81 (95% confidence interval 0.65–1.0), indicating a marginal negative association between this variant and coronary disease. The common lipoprotein lipasePvu II polymorphism shows no relation to coronary disease (summary odds ratio 0.90,95% confidence interval 0.80–1.01). The rare allele of the lipoprotein lipase HindIII polymorphism is negatively associated with coronary disease (summary odds ratio 0.84, 95% confidence interval 0.73–0.96). The lipoprotein lipase D9N allele is associated with high levels of triglyceride and low levels of high-density lipoprotein. Similar atherogenic lipid levels are observed in subjects with structural mutations lipoprotein lipase C188E and P207L. Carriers of the S447Ter allele have low levels of triglyceride. The lipoprotein lipase gene variants which decrease lipoprotein lipase catalytic activity are associated with familial combined hyperlipidemia, but not the elevation of apolipoprotein B seen in this disorder. In conclusion, allelic variants in the lipoprotein lipase gene are associated with altered lipid levels and differential coronary disease risk.     

2型糖尿病肾病患者血清脂蛋白(

目的探讨血清脂蛋白(a)[Lipoproteinl(a)]在2型糖尿病肾病中的临床意义.方法测定42例2型糖尿病病人及34例健康人的Lpa水平.根据其24 h尿白蛋白排泄率(UAER)多少将糖尿病患者分成三组非糖尿病肾病组(A1组)16例(UAER<20 μg/min);微量白蛋白尿组(A2组)15例(20 μg/min≤UAER<200 μg/min);大量白蛋白尿组(A3组)11例(UAER≥200 μg/min).B组健康正常人34例.结果2型糖尿病组Lpa水平显著高于正常对照组.A2组Lpa水平(176.25±40.13)高于A1组(107.61±36.30),且差异有显著性(P<0.05),A3组Lpa水平(308.21±59.65)进一步提高.Lpa与URER呈正相关(r=0.402,P<0.05).结论随着2型糖尿患者UAER的增高,Lpa有增高趋势.提示测定血清Lpa的水平可能间接反映2型糖尿病肾病的严重程度.     

脂蛋白(a)与动脉粥样硬化

脂蛋白(a)[lipoprotein(a),Lp(a)]是动脉粥样硬化(atherosclerosis,AS)和血栓形成的独立危险因素。本文就Lp(a)的分子结构、遗传基础及其致AS、促血栓形成的可能机制作一综述。     

Lipoprotein profiles in adult nephrotics.

Lipoproteins and lipoprotein profiles were determined in 96 adult nephrotic patients. The serum cholesterol-serum albumin, serum triglycerides-serum albumin and 24-hour urine protein loss-serum albumin values were all significantly inversely correlated. The serum triglycerides and serum cholesterol levels were not significantly lower in the group of lupus nephrotic patients compared to the nonlupus nephrotics. All lipoprotein types except type I were observed. The lipoprotein types fell into three nearly equal groups--IIa, IIb, and V. Type IV, the most common lipoprotein abnormality in uremic patients, was distinctly uncommon.