血管内皮细胞糖萼与脂蛋白

血管内皮细胞糖萼是位于内皮细胞表面的一层多糖蛋白复合结构,在内皮细胞表面形成选择性通透屏障。在对糖萼进行概述后,主要针对在流动剪切力作用下,糖萼与物质传输,尤其是与大分子物质如低密度脂蛋白(low density lipoprotein,LDL)的关系展开论述。其关系体现为:一方面,糖萼的厚度和完整性影响LDL的浓度极化及跨内膜输运;糖萼中的硫酸肝素蛋白聚糖参与残余脂蛋白代谢的全过程。另一方面,LDL的氧化产物ox-LDL会破坏内皮细胞糖萼层的主要成分硫酸肝素。研究糖萼与脂蛋白的关系,将为阐明动脉粥样硬化的发病机理提供新的线索,并为将糖萼作为新的防治靶点提供更多依据。     

Oxidized low density lipoproteins, statin therapy and severity of coronary artery disease

BACKGROUND: The impact of statin therapy on the association between circulating levels of oxidized low density lipoproteins (OxLDL) and severity of coronary artery disease (CAD) has not been studied. METHODS: OxLDLs were measured in 687 patients with angiographically proven CAD (320 patients, 46.6% on statin therapy and 367 patients, 53.4% not on statin therapy on admission) using the Mercodia Oxidized LDL Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Patients on statin therapy had lower levels of OxLDL (median [interquartile range]; 63.9 U/L [53.9; 79.8] versus 72.3 U/L [58.4; 86.1], P<0.001) and C-reactive protein (3.0 mg/L [1.2; 6.6] versus 4.0 mg/L [1.7; 13.1], P<0.001) than patients not on statins. Multivariable analysis showed that statin therapy was an independent predictor of lower levels of OxLDL (P=0.0001). In univariate analysis, OxLDL level did not differ significantly among the patients with 1-, 2-or 3-vessel disease (70.5 U/L [57.5; 85.6], 66.3 U/L [53.8; 82.6] and 68.2 U/L [57.0; 83.4], respectively, P=0.26). Multivariable logistic regression analysis showed that OxLDL was an independent correlate of angiographic severity of CAD (P=0.04) and that there was an interaction (P=0.038) between statins and OxLDL in that the increased levels of OxLDL were associated with more extensive CAD. CONCLUSION: Patients with CAD who receive statins have lower levels of OxLDL and an attenuation of the relationship between circulating levels of OxLDL and CAD severity compared with patients who do not receive statins.     

Insulin stimulates the uptake of chylomicron remnants in cultured rat hepatocytes

The effects of insulin (10-1000 microU ml-1) on chylomicron remnant uptake and degradation were studied in hepatocyte monolayer cultures. Both uptake and degradation were stimulated by insulin. The degree of stimulation was influenced by cell density, being most pronounced in sparse cultures. The uptake was stimulated in a dose-dependent fashion and was noticed already at a physiological insulin level (100 microU ml-1). At this insulin concentration uptake was stimulated by approximately 50% (range 26-84%). As suggested by the increase in Vmax for the remnant uptake, the number of lipoprotein receptors on the hepatocytes was increased by 100 microU ml-1 of insulin. Apolipoprotein-E-free low density lipoproteins (LDL) competed much less efficiently for the uptake of radioactive remnants than did unlabelled remnant particles. About half of the stimulatory effect of insulin on the remnant uptake could, however, be abolished by adding an excess of LDL, indicating that at least part of the stimulation by insulin was due to increased activity of the LDL receptor. This study thus shows that physiological insulin levels increase chylomicron remnant uptake in hepatocyte monolayer cultures. It is assumed that the effect of insulin is to increase the number of lipoprotein receptors at the cell surface, and at least part of the stimulation is due to an increase in LDL receptor activity.     

Apolipoprotein E polymorphisms and mortality in Italian type 2 diabetic patients

AIMS: To determine if apolipoprotein E polymorphism is associated with cardiovascular or all-cause mortality in Italian Type 2 diabetic patients. METHODS: A prospective study of mortality in Type 2 diabetic patients (n = 433) as a function of apolipoprotein E phenotype, which was assessed at entry into the study. During follow up (10 years), 110 (25.4%) patients died of which 66 (15.2%) were the result of cardiovascular causes. Cause of death was established from death certificates and clinical records. The clinical status of the survivors was determined at the end of the study. RESULTS: Apolipoprotein E polymorphisms were not associated with excess cardiovascular or all-cause mortality in the Italian Type 2 diabetic patients either in univariate or multivariate analyses. Age, duration of diabetes and glycated haemoglobin levels at entry were the primary determinants of premature mortality in the diabetic population. CONCLUSIONS: Apolipoprotein E polymorphisms are not markers for premature mortality in Italian Type 2 diabetic patients. The impact of apolipoprotein E mutations may be attenuated by environmental factors, notably a healthier diet, in Italian patients.     

Amino acids and lipoproteins in plasma of duodenopancreatectomized patients: effects of glucagon in physiological amounts

Duodenopancreatectomy induces a severe glucagon deficiency and elevated plasma concentrations of alanine, aspartate, glycine, proline, serine, arginine, citrulline, ornithine, phenylalanine and tyrosine. Restoring high physiological plasma glucagon in six such patients by infusing 0.3 mg/24 h of exogenous glucagon reduced significantly (P less than 0.01 or 0.001) the mentioned amino acids (except phenylalanine) and further asparagine, glutamine, methionine and threonine. In six normal subjects the same infusion reduced significantly (P less than 0.05 to 0.001) plasma alanine, asparagine, glutamate, glutamine, glycine, proline, serine, threonine, arginine, ornithine, lysine and tyrosine. However, the effect was significantly (P less than 0.01 or 0.001) less marked for alanine, glutamine, glycine, methionine, serine, threonine and arginine. This particular glucagon sensitivity of duodenopancreatectomized patients suggests that glucagon deficiency is the cause of their hyperaminacidaemia. By contrast, lipoprotein concentrations were virtually unaffected by either glucagon deficiency or its replacement. In the light of the marked hypoaminacidaemia in glucagonoma patients these results attribute to glucagon a major role as a regulator of protein metabolism.     

Hepatic and extrahepatic triglyceride lipase activity in uraemic patients on chronic haemodialysis.

In eleven patients with chronic renal insufficiency treated by intermittent haemodialysis and in ten normal subjects, hepatic and extrahepatic triglyceride lipase activity of post heparin plasma was selectively measured, utilizing the different sensitivity of both enzymes to inhibition by protamine sulphate. In uraemic patients, hepatic triglyceride lipase activity was significantly decreased and extrahepatic triglyceride lipase activity was normal when compared with the control group. The uraemic subjects showed a moderate hypetriglyceridaemia; their serum cholesterol level, however, was normal. The high triglyceride concentration was due to an increase of very low density lipoproteins and low density lipoproteins of the density between 1.006 and 1.019 g/ml (LDL1). The concentration of low density lipoproteins of the density between 1.019 and 1.063 g/ml (LDL2) was decreased. LDL2 were relatively rich in triglycerides when compared with LDL2 from the control group.     

Association between serum cholesterol levels and Alzheimer’s disease in China: a case-control study

To examine the association between blood cholesterol concentrations and Alzheimer’s disease (AD) in the Chinese elderly. A case-control study was implemented between November 2011 and November 2017. Elderly patients aged ≥?55?years with (n?=?117) and without AD (control participants; n?=?117) were recruited from the Neurology Central Hospital of Tianjin, China. The associations between AD and blood parameters were assessed using multiple binary logistic regression analyses adjusted for multiple covariates. Higher serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and lower serum high-density lipoprotein cholesterol (HDL-C) levels associated with AD risk in the models adjusted for (1) age, sex and education; and (2) further adjusted for body mass index, smoking status, stroke, hypertension, type 2 diabetes mellitus and heart disease. Increased serum TC and LDL-C levels and lower HDL-C levels were independently associated with the risk of AD.     

One Egg per Day Improves Inflammation when Compared to an Oatmeal-Based Breakfast without Increasing Other Cardiometabolic Risk Factors in Diabetic Patients

There is concern that egg intake may increase blood glucose in patients with type 2 diabetes mellitus (T2DM). However, we have previously shown that eggs reduce inflammation in patients at risk for T2DM, including obese subjects and those with metabolic syndrome. Thus, we hypothesized that egg intake would not alter plasma glucose in T2DM patients when compared to oatmeal intake. Our primary endpoints for this clinical intervention were plasma glucose and the inflammatory markers tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). As secondary endpoints, we evaluated additional parameters of glucose metabolism, dyslipidemias, oxidative stress and inflammation. Twenty-nine subjects, 35–65 years with glycosylated hemoglobin (HbA1c) values <9% were recruited and randomly allocated to consume isocaloric breakfasts containing either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day for five weeks. Following a three-week washout period, subjects were assigned to the alternate breakfast. At the end of each period, we measured all primary and secondary endpoints. Subjects completed four-day dietary recalls and one exercise questionnaire for each breakfast period. There were no significant differences in plasma glucose, our primary endpoint, plasma lipids, lipoprotein size or subfraction concentrations, insulin, HbA1c, apolipoprotein B, oxidized LDL or C-reactive protein. However, after adjusting for gender, age and body mass index, aspartate amino-transferase (AST) (p < 0.05) and tumor necrosis factor (TNF)-α (p < 0.01), one of our primary endpoints were significantly reduced during the egg period. These results suggest that compared to an oatmeal-based breakfast, eggs do not have any detrimental effects on lipoprotein or glucose metabolism in T2DM. In contrast, eggs reduce AST and TNF-α in this population characterized by chronic low-grade inflammation.