丝裂原活化蛋白激酶在动脉粥样硬化中作用的相关性研究

动脉粥样硬化(AS)是动脉的慢性炎性疾病。AS由炎症引发血管内皮细胞活化,包括释放细胞因子,粘附分子,基质金属蛋白酶和其它调节炎性介质(包括NO),导致血管内皮细胞功能紊乱和损伤,这是早期AS泡沫细胞形成的关键因素之一。丝裂原活化蛋白激酶(MAPKs)是调控炎症和抗炎反应重要的信号通路。激活的MAPKs,特别是ERK、JNK和p38 MAPKs,参与调节粘附分子和基质金属蛋白酶的表达。靶向给予ERK,JNK和p38 MAPKs信号通路抑制剂,其临床前研究数据表明它们有抗炎活性。因此,MAPKs的特异性抑制剂有望成为一种新的减轻动脉粥样化形成的治疗方法。     

不同剂量阿托伐他汀对急性心肌梗死患者血浆致动脉硬化指数及预后的影响

目的 探讨不同剂量阿托伐他汀对急性心肌梗死(AMI)患者血浆致动脉硬化指数(AIP)及主要不良心血管事件(MACE)的影响。方法 选取2015年1月至2016年1月于我院心内科住院主要诊断为AMI并完成随访的患者212例。随机分为标准治疗组(106例)和强化治疗组(106例),所有患者予以AMI的常规治疗。标准治疗组同时予以阿托伐他汀20mg/d 口服;强化治疗组同时予以阿托伐他汀40mg/d口服,随访1年。比较两组患者治疗前后血脂、AIP、脉搏波传导速度(PWV)等指标的变化及MACE的发生。结果 AMI患者AIP与PWV呈显著的正相关(r=0.801,P＜0.05);与治疗前比较,两组患者AIP、PWV、血脂等生化指标水平均降低,且仅强化治疗组患者颈动脉内中膜厚度减少,差异有统计学意义(P﹤0.05);与标准治疗组比较,强化治疗组AIP、PWV、血脂等指标变化更为显著,差异有统计学意义(P﹤0.05),而两组不良反应发生率比较,差异无统计学意义(P﹥0.05);治疗1年后两组患者总的MACE发生比较,差异有统计学意义(P﹤0.05)。结论 阿托伐他强化治疗AMI不仅可进一步降低患者血脂水平,还有更好的抗动脉硬化作用,降低AMI后MACE的发生,值得临床推广应用。     

Lipoprotein (a), metabolic syndrome and coronary calcium score in a large occupational cohort

Background and aimsWhether lipoprotein (a) [Lp(a)] concentration is associated with metabolic syndrome (MetS) and pre-clinical atherosclerosis in different ethnic groups is uncertain. The association between Lp(a), MetS and a measure of pre-clinical atherosclerosis was studied in a large Asian cohort.Methods and resultsData were analyzed from a South Korean occupational cohort who underwent a cardiac computed tomography (CT) estimation of CAC score and measurements of cardiovascular risk factors (n = 14,583 people). The key exposure was an Lp(a) concentration in the top quartile (>38.64 mg/dL)) with a CAC score >0 as the outcome variable and measure of pre-clinical atherosclerosis. Logistic regression was used to describe the associations. 1462 participants had a CAC score >0. In the lowest Lp(a) quartile (<11.29 mg/dL), 25.8% had MetS, compared with 16.1% in the highest Lp(a) quartile (>38.64 mg/dL (p < 0.001). MetS, and component features, were inversely related to Lp(a) concentration (all p < 0.0001). In the highest Lp(a) quartile group, there was an association between Lp(a) and CAC score >0 in men (OR 1.21[1.05, 1.40], p = 0.008), and women (OR 1.62[1.03, 2.55], p = 0.038), after adjustment for age, sex, lipid lowering therapy, and multiple cardiovascular risk factors. There was no evidence of an interaction between highest quartile Lp(a) and either high LDLc (>147 mg/dL) (p = 0.99), or MetS (p = 0.84) on the association with CAC score >0.ConclusionLp(a) levels are inversely related to MetS and its components. There was a robust association between Lp(a) concentration >38.6 mg/dL and marker of early atherosclerosis in both men and women, regardless of LDLc, level MetS or other cardiovascular risk factors.     

Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: A clinical update

Cardiovascular disease (CVD) is a significant cause of death in Europe. In addition to patients with proven CVD, those with type 2 diabetes (T2D) are at a particularly high-risk of CVD and associated mortality. Treatment for dyslipidaemia, a principal risk factor for CVD, remains a healthcare priority; evidence supports the reduction of low-density lipoprotein cholesterol (LDL-C) as the primary objective of dyslipidaemia management.While statins are the treatment of choice for lowering LDL-C in the majority of patients, including those with T2D, many patients retain a high CVD risk despite achieving the recommended LDL-C targets with statins. This ‘residual risk’ is mainly due to elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. Following statin therapy optimisation additional pharmacotherapy should be considered as part of a multifaceted approach to risk reduction. Fibrates (especially fenofibrate) are the principal agents recommended for add-on therapy to treat elevated TG or low HDL-C levels. Currently, the strongest evidence of benefit is for the addition of fenofibrate to statin treatment in high-risk patients with T2D and dyslipidaemia. An alternative approach is the addition of agents to reduce LDL-C beyond the levels attainable with statin monotherapy.Here, addition of fibrates and niacin to statin therapy is discussed, and novel approaches being developed for HDL-C and TG management, including cholesteryl ester transfer protein inhibitors, Apo A-1 analogues, mipomersen, lomitapide and monoclonal antibodies against PCSK9, are reviewed.     

Correlation between Plaque Composition as assessed by Virtual Histology and C-reactive Protein

Background

Previous studies have shown that coronary plaque composition plays a pivotal role in plaque instability, and imaging modalities and serum biomarkers have been investigated to identify vulnerable plaque. Virtual histology IVUS (VH-IVUS) characterizes plaque components as calcified, fibrotic, fibrofatty, or necrotic core. C-reactive protein (hsCRP) is an independent risk factor and a powerful predictor of future coronary events. However, a relationship between inflammatory response indicated by CRP and plaque characteristics in ACS patients remains not well established.

Objective

To determine, by using VH-IVUS, the relation between coronary plaque components and plasma high-sensitivity CRP levels in patients with acute coronary syndromes (ACS).

Methods

52 patients with ACS were enrolled in this prospective study. Electrocardiographically-gated VH-IVUS were performed in the culprit lesion before PCI. Blood sample was drawn from all patients before the procedure and after 24 hours, and hs-CRP levels were determined.

Results

Mean age was 55.3±4.9 years, 76.9% were men and 30.9% had diabetes. Mean MLA was 3.9±1.3 mm², and plaque burden was 69±11.3%, as assessed by IVUS. VH-IVUS analysis at the minimum luminal site identified plaque components: fibrotic (59.6±15.8%), fibrofatty (7.6±8.2%), dense calcium (12.1±9.2%) and necrotic core (20.7±12.7%). Plasma hs-CRP (mean 16.02±18.07 mg/L) did not correlate with necrotic core (r=-0.089, p = 0.53) and other plaque components.

Conclusions

In this prospective study with patients with ACS, the predominant components of the culprit plaque were fibrotic and necrotic core. Serum hs C-reactive protein levels did not correlate with plaque composition.     

Circulating microparticles and microRNAs as players in atherosclerosis

Microparticles (MPs) are extracellular membrane vesicles released from normal, apoptotic and pathological cells following a process of detachment from cells of origin. MPs are typically defined by their size, exposure of phosphatidylserine, the expression of surface antigens, proteins and genetic material, originating from their donor cells, and as important vehicles of intercellular communication across numerous biological processes. MPs contain the major source of systemic RNA including microRNA (miRNA) of which aberrant expression appears to be associated with stage and progression of atherosclerosis. The involvement and influence of miRNA during the onset and progression of atherosclerotic disease have generated a lot of interest in assessing the feasibility of therapeutic regulation of miRNAs to manipulate them with a special focus on cardiovascular disease. We speculate on the future developments of MPs which contain miRNA as new therapeutic targets for proliferative vascular diseases such as atherosclerosis.     

颈动脉粥样硬化对冠心病诊断的价值

目的 探讨颈动脉粥样硬化与冠状动脉样硬化的关系从而了解颈动脉粥样硬化对冠心病的诊断价值。方法 通过对同一患行颈动脉超声及冠状动脉造影检查，根据冠状动脉造影结果分为阴性组和阳性组，并将阳性组分为一支病变组，二支病变组和三支病变组。通过超声测定和因管后壁内中膜厚度（IMT），斑块厚度并计算斑块积分，对各组IMT及斑块积分进行统计等处理。结果 颈动脉粥样硬化对冠心病有预测价值。阳性组的IMT及斑块积分均大于阴性组。右侧颈动脉组的预测性较左侧略高。结论 颈动脉粥样硬化对冠心病的预测价值很大。     

糖尿病大鼠糖基化终产物与主动脉细胞外基质成分的关系

为探讨糖基化终产物在糖尿病大鼠动脉粥样硬化发生中对主动脉细胞外基质成分生成增加所起的作用,本实验将糖尿病大鼠、糖尿病＋ 氨基胍治疗大鼠和正常大鼠分别喂养１、２、３ 和４ 个月后,测定其血红蛋白－ 糖基化终产物及主动脉壁Ⅲ型前胶原、Ⅳ型胶原、Ⅳ型胶原－ 糖基化终产物及层粘蛋白含量。结果发现,糖尿病组大鼠各时相点血红蛋白－ 糖基化终产物（１ ～４ 个月分别为６．８８±１ ．２３、１０ ．２６±０．６３、１５．３±１．４９ 和１８．５７ ±２．９０ ｋｕｇ, 与血糖水平相关）、Ⅲ型前胶原（１ ～４个月分别为１５．２０±３．０３ 、２１．４４ ±１．７９、２７．１９±３ ．２８ 和３３．９９±４ ．９６ μｇＬ, 与血红蛋白－ 糖基化终产物和Ⅳ型胶原－ 糖基化终产物相关） 、Ⅳ型胶原（１～４ 个月分别为２３．６７±１．４９、３０．３７ ±２ ．８６、３６．６５ ±１．９８ 和４５．４６±５．７７ μｇＬ, 与血红蛋白－ 糖基化终产物和Ⅳ型胶原－ 糖基化终产物相关）、Ⅳ型胶原－ 糖基化终产物（１～４ 个月分别为０．７９ ±０．１５、１．２５ ±０．２２ 、１．５４ ±０．０６ 和１．８０±０ ．１４ Ｍｕｇ, 与血红蛋白－ 糖基化终产物和Ⅳ型胶原相关）      

同型半胱氨酸对内皮细胞及脂质过氧化的影响

为观察同型半胱氨酸对内皮细胞,内皮细胞一氧化氮系统及脂质过氧化的影响,在培养兔主动脉内皮细胞中加入兔天然低密度脂蛋白后分为七组;对照组不加任何药物,叶酸组;四氢喋呤ＢＨ４）组,一氧化氮供体药ＳＩＮ－１组,同型半胱氨酸组;同型半胱氨酸加叶酸组和同型半胱氨酸加四氢喋呤组。     

表达反义单核细胞趋化蛋白-1的重组逆转录病毒对家兔动脉平滑肌单核细胞趋化蛋白-1基因表达的影响

为研究反义单核细胞真挚化蛋白－１转基因表达对单核细胞进入动脉壁的作用,首先,构建了表达反义单核细胞趋化蛋白－１基因的逆转录病道理毒重组体,并观察它在培养的细胞中的表达。将家多单核细胞趋化蛋白－１ｃＤＮＡ反向插入到ｐＬＮＣＸ,构成ＬＮＣＸ－ａｎｔｉ－ＭＣＰ－１重组病毒质粒。再将重组质粒转染Ψ－２细胞,继以Ψ－２细胞产生的病毒上清感染ＰＡ３１７细胞,取得Ｇ４１８ＰＡ３１７抗细胞克隆。上述细胞经扩增培养