Peripheral arterial disease,type 2 diabetes and postprandial lipidaemia: Is there a link?

Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index 0.9, is present in at least one in every four patients with type 2 diabetes mellitus.Several reasons exist for peripheral arterial disease indiabetes. In addition to hyperglycaemia, smoking and hypertension, the dyslipidaemia that accompanies type2 diabetes and is characterised by increased triglyceride levels and reduced high-density lipoprotein cholesterol concentrations also seems to contribute to this association. Recent years have witnessed an increased interest in postprandial lipidaemia, as a result of various prospective studies showing that non-fasting triglycerides predict the onset of arteriosclerotic cardiovascular disease better than fasting measurements do. Additionally,the use of certain specific postprandial particle markers,such as apolipoprotein B-48, makes it easier and more simple to approach the postprandial phenomenon. Despite this, only a few studies have evaluated the role of postprandial triglycerides in the development of peripheral arterial disease and type 2 diabetes. The purpose of this review is to examine the epidemiology and risk factors of peripheral arterial disease in type 2 diabetes, focusing on the role of postprandial triglycerides and particles.     

Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?

The cascade of molecular events leading to Human apolipoprotein A–I (apoA–I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants of apoA–I were described as inducing amyloidosis, but the mechanisms driving their aggregation and deposition are still unclear. We previously identified that the mutant Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen species from cultured RAW 264.7 murine macrophages, suggesting that part of the pathogenic pathway could elicit of an inflammatory signal. In this work we gained deep insight into this mechanism and determined that Gly26Arg induced a specific pro-inflammatory cascade involving activation of NF-κB and its translocation into the nucleus. These findings suggest that some but not all apoA–I natural variants might promote a pro-oxidant microenvironment which could in turn result in oxidative processing of the variants into a misfolded conformation.     

APOLIPOPROTEIN E PHENOTYPE IN DEMENTED PATIENTS IN GREEK POPULATION

Apolipoprotein E is a plasma protein, involved in the transport of lipids and their metabolism. The aim of this investigation was to correlate the ApoE phenotypes with the type and the severity of dementia in Greek demented patients.

The investigation revealed that 72% of the patients have the E3/3 phenotype, but only 11% of them demonstrated the E3/2; 13% of the patients have the E4/3 phenotype and only 4% of them demonstrated the phenotype E4/4. The most severely demented patients corresponded to e4 alléle. The present results indicate that the most common ApoE phenotype in Greek demented patients is E3/3.     

Homozygosity for a partial deletion of apoprotein A-V signal peptide results in intracellular missorting of the protein and chylomicronemia in a breast-fed infant

Deficiency of apoprotein A-V (apoA-V) can cause hypertriglyceridemia. In an 11 months old boy presenting with a severe hypertriglyceridemia, a formerly unknown 24 nucleotide deletion in exon 2 of the APOA5 gene was detected. The homozygous mutation results in an eight amino acid loss in the signal peptide sequence (c.16_39del; p.Ala6_Ala13del). Screening of control persons proved that this deletion is a rare mutation. Hypertriglyceridemia in the patient was only found at the time when he was breast fed, while after weaning, triglyceride levels were close to normal. Under both dietary conditions, apoA-V protein was undetectable in plasma while post-heparin plasma lipoprotein lipase activity was normal.     

Use of the plasma triglyceride/high-density lipoprotein cholesterol ratio to identify cardiovascular disease in hypertensive subjects

This analysis evaluated the hypothesis that the plasma triglyceride (TG)/high–density lipoprotein cholesterol (HDL-C) concentration ratio can help identify patients with essential hypertension who are insulin–resistant, with the cardiovascular disease (CVD) risk profile associated with that defect. Data from a community–based study developed between 2003 and 2012 were used to compare CVD risk factors and outcome. Plasma TG/HDL-C cut–points of 2.5 (women) and 3.5 (men) subdivided normotensive (n = 574) and hypertensive (n = 373) subjects into “high” and “low” risk groups. Metabolic syndrome criteria (MetS) were also used to identify “high” and “low” risk groups. The baseline cardio–metabolic profile was significantly more adverse in 2003 in “high” risk subgroups, irrespective of BP classification or definition of risk (TG/HDL-C ratio vs. MetS criteria). Crude incidence of combined CVD events increased across risk groups, ranging from 1.9 in normotensive–low TG/HDL-C subjects to 19.9 in hypertensive–high TG/HDL-C ratio individuals (P for trends <.001). Adjusted hazard ratios for CVD events also increased with both hypertension and TG/HDL-C. Comparable findings were seen when CVD outcome was predicted by MetS criteria. The TG/HDL-C concentration ratio and the MetS criteria identify to a comparable degree hypertensive subjects who are at greatest cardio–metabolic risk and develop significantly more CVD.     

银杏叶提取物EGb761对铜与高胆固醇共处理家兔主动脉病变的影响

目的 观察银杏叶提取物EGb761对铜和高胆固醇诱导的家兔主动脉病变的保护作用.方法 采用Sparks的方法复制铜和高胆固醇家兔模型,EGb761以50 mg·kg-1·d-1的剂量灌胃3 w后,苏丹Ⅲ和HE染色观察主动脉的大体和镜下形态改变,图像分析测量动脉粥样硬化面积占主动脉面积的百分比,酶法检测血清总胆同醇(TC)、甘油三酯( TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,硫代巴比妥酸( TBA)法测定血清丙二醛(MDA)水平,实时定量RT-PCR法检测肝组织LDLR和LR PI mRNA表达.结果 模型组主动脉可见明显的动脉粥样硬化改变,EGb761组动脉粥样硬化病变较模型组减轻,图像分析结果显示,EGb761组斑块面积百分比显著降低,与模型组相比差别具有统计学意义(P＜0.05).模型组血清TC、TG、HDL-C、LDL-C和MDA水平均显著升高,与正常组相比差别具有统计学意义(P＜0.05);EGb761组血清LDL-C和MDA水平均显著降低,与模型组相比差别具有统计学意义(P＜0.05).EGb761组肝组织LRPI mRNA表达显著升高,与模型组相比差别具有统计学意义(P＜0.05).结论 EGb761具有改善动脉粥样硬化病变的作用,其作用机制与调节血脂水平和抗过氧化损伤有关.     

冠心病家族史大学生apo E基因多态性的临床研究

目的:探讨大学生载脂蛋白E(apoE)基因多态性,及其对血脂代谢紊乱、动脉粥样硬化(AS)和冠心病(CHD)的影响。方法:对广东地区高校152名健康汉族大学生,在问卷调查的基础上,根据一、二级亲属有无CHD病史分为阳性组与对照组,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行apoE基因分析。结果:有CHD家族史的阳性组e_4等位基因频率显著高于无CHD家族史的阴性组(P<0.05)。结论:apoE基因多态性与AS、CHD易感性密切有关,e_4可能是CHD的重要遗传因子。     

Prognostic value of apolipoprotein B and A-I in the prediction of myocardial infarction in middle-aged men and women: results from the MONICA/KORA Augsburg cohort study.

AIMS: To investigate the association between apolipoprotein B (apoB), A-I (apoA-I), the apoB/apoA-I ratio, and the incidence of coronary events. METHODS AND RESULTS: Analysis included 1414 men and 1436 women aged 35-64 years without a prior coronary event who participated in the population-based MONICA Augsburg survey 1984-85 (median followed-up period 13 years). Incidence of fatal and non-fatal myocardial infarction, and sudden cardiac death was assessed using data of the MONICA/KORA Augsburg coronary event registry. During follow-up, 114 incident coronary events occurred in men and 31 in women. In multivariable analysis, an increase of 1 standard deviation in the serum concentration of apoB was associated with an increased risk of coronary events in men [hazard ratio (HR)=1.49; 95% confidence interval (CI); 1.25-1.78] and in women (HR=1.73; 95% CI; 1.32-2.27). By contrast, elevated concentrations of apoA-I were not associated with a significantly decreased risk of coronary events in either sex (HR=0.91). Furthermore, the predictive power of the apoB/apoA-I ratio was similar to that of the total cholesterol/HDL cholesterol ratio in men and women. CONCLUSION: ApoB and the apoB/apoA-I ratio were strong predictors of coronary events in middle-aged men and women, whereas apoA-I did not add significantly to the estimation of future coronary risk.