Inflammatory status modulates plasma lipid and inflammatory marker responses to kiwifruit consumption in hypercholesterolaemic men

Background and aimsKiwifruit has the potential to improve markers of metabolic dysfunction, but the response may be influenced by inflammatory state. We aimed to investigate whether inflammatory state would modulate the effect of consuming two green kiwifruit daily on plasma lipids and markers of inflammation.Methods and resultsEighty-five hypercholesterolaemic men completed a 4-week healthy diet run-in, before randomisation to a controlled cross-over study of two 4-week interventions of two green kiwifruit/day plus healthy diet (intervention) or healthy diet alone (control). Anthropometric measures and fasting blood samples (plasma lipids, serum apolipoproteins A1 and B, high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, tumour necrosis factor-alpha (TNF-α) and IL-10) were taken at baseline, 4 and 8 weeks. Subjects were divided into low and medium inflammatory groups, using pre-intervention hs-CRP concentrations (hs-CRP <1 and 1–3 mg/L, respectively).In the medium inflammatory group the kiwifruit intervention resulted in significant improvements in plasma high-density lipoprotein cholesterol (HDL-C) (mean difference 0.08 [95% CI: 0.03, 0.12] mmol/L [P < 0.001]), total cholesterol (TC)/HDL-C ratio (−0.29 [−0.45, −0.14] mmol/L [P = 0.001]), plasma hs-CRP (−22.1 [−33.6, −4.97]% [P = 0.01]) and IL-6 (−43.7 [−63.0, −14.1]% [P = 0.01]) compared to control treatment. No effects were seen in the low inflammatory group. There were significant between inflammation group differences for TC/HDL-C (P = 0.02), triglyceride (TG)/HDL-C (P = 0.05), and plasma IL-6 (P = 0.04).ConclusionsInflammatory state modulated responses to the kiwifruit intervention by improving inflammatory markers and lipid profiles in subjects with modestly elevated CRP, suggesting this group may particularly benefit from the regular consumption of green kiwifruit.Registered 16th March 2010, Australian New Zealand Clinical Trials Registry (no. ACTRN12610000213044), www.ANZCTR.org.au.     

MicroRNA-27a/b regulates cellular cholesterol efflux,influx and esterification/hydrolysis in THP-1 macrophages

Rationale

Macrophage cholesterol homeostasis maintenance is the result of a balance between influx, endogenous synthesis, esterification/hydrolysis and efflux. Excessive accumulation of cholesterol leads to foam cell formation, which is the major pathology of atherosclerosis. Previous studies have shown that miR-27 (miR-27a and miR-27b) may play a key role in the progression of atherosclerosis.

Objective

We set out to investigate the molecular mechanisms of miR-27a/b in intracellular cholesterol homeostasis.

Methods and results

In the present study, our results have shown that the miR-27 family is highly conserved during evolution, present in mammals and directly targets the 3′ UTR of ABCA1, LPL, and ACAT1. apoA1, ABCG1 and SR-B1 lacking miR-27 bind sites should not be influenced by miR-27 directly. miR-27a and miR-27b directly regulated the expression of endogenous ABCA1 in different cells. Treatment with miR-27a and miR-27b mimics reduced apoA1-mediated cholesterol efflux by 33.08% and 44.61% in THP-1 cells, respectively. miR-27a/b also regulated HDL-mediated cholesterol efflux in THP-1 macrophages and affected the expression of apoA1 in HepG2 cells. However, miR-27a/b had no effect on total cellular cholesterol accumulation, but regulated the levels of cellular free cholesterol and cholesterol ester. We further found that miR-27a/b regulated the expression of LPL and CD36, and then affected the ability of THP-1 macrophages to uptake Dil-oxLDL. Finally, we identified that miR-27a/b regulated cholesterol ester formation by targeting ACAT1 in THP-1 macrophages.

Conclusion

These findings indicate that miR-27a/b affects the efflux, influx, esterification and hydrolysis of cellular cholesterol by regulating the expression of ABCA1, apoA1, LPL, CD36 and ACAT1.     

运动和灌胃左旋肉碱?大豆肽对肥胖大鼠载脂蛋白的影响

目的:研究有氧运动和灌胃左旋肉碱、大豆肽混合溶液6周对单纯性肥胖大鼠Lee's指数及载脂蛋白的影响.方法:以通过建模成功后的SD肥胖大鼠为研究对象,通过6周跑台训练和每日灌胃10%的营养液[600 mg/(kg·d)左旋肉碱和15 mg/(kg·d)大豆肽],肥胖对照组每只灌胃2 ml/d蒸馏水.观察肥胖大鼠的体重、体长,计算Lee's指数,检测实验大鼠体重、体长、载脂蛋白浓度等指标.结果:实验结束后,单纯运动干预组、单纯营养干预组和运动 营养干预组的Lee's指数明显低于肥胖对照组,两者比较差异均有显著性(P＜0.05),但3个实验组之间无差异(P＞0.05);营养干预、运动干预组、运动 营养干预都明显地降低了apoB的水平(P＜0.05);单纯运动干预和单纯营养干预对肥胖大鼠的apoA影响均没有显著性变化(P＞0.05),而运动 营养干预对肥胖大鼠apoA的影响差异有显著性(P＜0.05).结论:通过8周喂养高脂高糖饲料成功建立了肥胖大鼠模型.运动与营养干预能改善脂质代谢,显著降低肥胖大鼠apoB浓度,升高apoA浓度.     

apoB/apoA1比值预测血管疾病风险的研究进展

血脂异常是动脉粥样硬化性心血管疾病(ACVD)最重要的危险因素之一,与其发生、发展和预后等有密切关系.TC、LDL-C、HDL-C和TG已列为临床实验室的常规血脂检测项目.有没有可能将临床脂质相关风险评估简化并将载脂蛋白作为一个危险标志物和降脂治疗的新靶点呢?近年来,国外发表了大量有关载脂蛋白A1(apoA1)、载脂蛋白B(apoB)的长期前瞻性和回顾性研究,其中包括相当数量的大规模国家性甚至国际性的临床调查.结果显示apoA1、apoB及apoB/apoA1比值在预测心血管疾病方面更优于常规脂质谱测定.因此,反映致动脉粥样硬化脂蛋白颗粒总和的ApoB和反映抗动脉粥样硬化HDL颗粒总和的apoA1可能比LDL-C和其他常规脂质指标更能准确反映心血管事件风险.     

Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study

Background and aimsType 2 diabetes mellitus (T2DM) is a condition defined by hyperglycaemia, but also often presents with dyslipidaemia and suppressed HDL cholesterol. Mendelian randomization studies have suggested a causal link between low HDL cholesterol and T2DM. However, influences of gender, polymorphisms and lifestyle, all known to influence HDL cholesterol, have not been fully explored in a prospective cohort.Methods and resultsIn 2001–2002, a random sample of 1514 males (18–87 years old) and 1528 females (18–89 years old) were recruited in the ATTICA study. The 10-year follow-up (2011–2012) included 1485 participants. Lipids and lipoproteins levels, glucose and insulin levels were measured together with apolipoprotein A1 (apoA1) 75 G/A genotype, which is known to influence HDL-cholesterol. In total, 12.9% of the study sample developed T2DM within the 10-year follow-up period. In multivariable models, for each mg/dL increase in apoA1 levels in males, 10-year T2DM risk decreased 1.02%; while every unit increase in apoB/LDL-cholesterol ratio increased risk 4-fold. Finally, for every unit increase in triglycerides/apoA1 ratio, the risk increased 85%. HOMA-IR independently predicted T2DM 10-year incidence only for carriers of GG polymorphism (all, p < 0.05), but not in carriers of the GA polymorphism (all, p > 0.05).ConclusionApoA1 was associated with decreased T2DM risk and TG/ApoA1 and apoB/LDL were associated with increased risk of T2DM, only in males. ApoA1 polymorphism, which is associated with lower HDL cholesterol, influenced the predictive effects of HOMA-IR on T2DM incidence, which appeared to be moderated by physical activity, suggesting potential scope for more targeted preventative strategies.     

Association between apolipoprotein E polymorphism and serum lipid and apolipoprotein levels with Alzheimer's disease

We have recently demonstrated that apolipoprotein E (APOE)-varepsilon4 allele is a risk factor for Alzheimer disease (AD) in Tehran, Iran. The current study specifically aimed to examine whether APOE polymorphism in association with serum lipids-apolipoprotein level is a risk factor for AD in a population from Tehran, Iran. APOE polymorphism and plasma lipids, apoA1, apoB and lipoprotein (a) (Lp(a)) levels were determined in 94 AD patients and 111matched controls. Our study demonstrated a significant association between APOE polymorphism and the level of plasma lipids and apolipoprotein with AD in this population. The AD subjects had significantly lower apoA1 (p<0.001) and HDL-C (p<0.01) and higher apoB (p=0.01) and LDL-C (p=0.02) levels than that of the control group. The AD subjects carrying APOE-varepsilon4 allele had lower plasma apoA1 (t=5.2, p<0.002) and HDL-C level (t=2.7, p=0.01) but had higher plasma apoB (t=-5.4, p<0.002), LDL-C (t=-4.6, p=0.005) and total cholesterol (TC) (t=-2.7, p=0.01) than that of the non APOE-varepsilon4 carriers. These results indicated that AD patients with APOE-varepsilon4 allele has a distinct plasma lipid profile and carrier of this allele with low levels of apoA1 and HDL-C may be more susceptible to AD.     

人载脂蛋白AⅠ的分离纯化

目的探索一种相对简便而高效的方法,从人血清中分离纯化载脂蛋白AⅠ（apoAⅠ）,得到高纯度的apoAⅠ。方法人血清利用溴化钾密度梯度离心、盐酸胍处理、透析后亲和层析,用SDS-聚丙烯酰胺凝胶电泳和双向免疫扩散试验鉴定分离得到的蛋白。结果最后获得的apoAⅠ抗原纯度达到电泳纯和免疫纯。结论该方法简便,分离效果好、特异性高。     

活体情况下评价载脂蛋白A1对小鼠视网膜血管生成的影响

用眼底照相及荧光造影探讨载脂蛋白A1（apoA1）正常生理状态下及缺氧状态下对小鼠视网膜血管生长情况的影响。     

eGFR 评价高血压合并冠心病患者肾功能与载脂蛋白 A 的关系

目的 通过eGFR评价高血压合并冠心病患者肾功能与载脂蛋白A(apoA)的关系。方法 纳入2011年3月—2012年12月入住安徽医科大学第一附属医院心内科行冠脉造影检查诊断为冠心病或临床诊断冠心病但因肾功能较差不能耐受冠脉造影检查(13例)的高血压患者共341例,使用简化MDRD公式计算各患者肾小球滤过率(eGFR),根据eGFR高低将其分为eGFR正常组291例(eGFR≥60 mL·min-1·1.73 m-2)和eGFR下降组50例(eGFR＜60 mL·min-1·1.73 m-2)。统计分析患者年龄、性别、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、LDL/HDL、载脂蛋白A(apoA),载脂蛋白B(apoB),apoA/apoB,白蛋白(ALB),脂蛋白a(lpa),血肌酐(SCr),糖尿病患者比例,吸烟比例,比较两组数据差异,并用Logistic回归分析上诉指标对eGFR下降的影响。结果 341例高血压合并冠心病患者中,平均年龄(65.04±10.62)岁,其中男性212例(62.1%)。eGFR下降组患者年龄,LDL/HDL、SCr、BUN、糖尿病比例、吸烟比例均高于eGFR正常组,apoA、apoA/apoB、HDL、ALB低于eGFR正常组,差异均有统计学意义(P＜0.05)。Logistic回归分析显示患者BUN(OR=1.712,P＜0.01),糖尿病比例(OR=5.100,P＜0.01),吸烟比例(OR=5.004,P＜0.01),apoA(OR=0.127,P＜0.01)为影响eGFR下降的独立因素,其中apoA的相关性最强。结论 apoA与高血压合并冠心病患者eGFR下降强相关,为独立的保护因素。     

血脂分析注意的几个问题

现代医学研究表明,血脂代谢异常与动脉粥样硬化（AS）的发生和发展有密切的关系,而且对冠心病急性事件（不稳定型心绞痛、急性心肌梗塞和冠脉猝死）的发作起重要作用。近年来一系列大规模的临床试验业已肯定,降低血浆胆固醇水平是冠心病一级和二级预防有关测定项目日益增多,血脂、脂蛋白、载脂蛋白测定已广泛应用于心血管病流行病学与l临床。测定血脂的目的是评估血脂水平对AS性疾病发生的危险程度,而不是用于AS性疾病（如冠心病）的诊断。但对于高脂蛋白血症与异常脂蛋白血症,血脂测定则为必要的诊断指标。在血脂的认识上常存在一些误区,一些影响测定结果的因素常被忽视,往往会造成治疗上的错误应用。