类风湿性关节炎患者microRNA-146a的表达及与血清学指标的相关性

类风湿性关节炎(rheumatoid arthritis,RA)是常见的以关节滑膜慢性炎症为主要特征的自身免疫性疾病,其主要病理改变为关节滑膜明显增厚并有大量炎症细胞浸润,血管翳形成以及软骨组织的侵蚀与破坏[1].microRNA可被分泌释放到细胞外,参与多种炎性和自身免疫性疾病的发病过程[2].Micro-RNAs (miRNAs)是一类短的(大约20 ～ 22个核苷酸)非编码RNA,介导RNA干扰和在翻译水平抑制蛋白表达.miRNAs与自身免疫性疾病进程有关且可能参与RA新的调控机制[2-4].     

类风湿性关节炎患者血清中结缔组织生长因子水平分析

目的研究类风湿性关节炎(RA)患者血清中结缔组织生长因子(CTGF)的水平,分析其临床意义。方法采用ELISA检测40例RA患者和20例正常对照者血清中CTGF水平,并分析与RA患者各临床和实验室指标相关性。结果 RA组患者血清的CTGF水平高于健康对照组。在DAS28≥5.1的RA高疾病活动度组患者血清CTGF水平高于DAS285.1的中低疾病活动度组患者。RA的血清CTGF水平与类风湿因子水平呈正相关,与血沉、C反应蛋白(CRP)、DAS28评分无明显相关性。结论 RA患者尤其高疾病活动度组RA患者血清CTGF水平明显升高,与RF水平呈正相关。     

血浆脂蛋白（a）水平与冠心病相关性分析

目的观察血浆脂蛋白（a）[LP（a）]水平与冠心病的相关性。方法入选住院并行选择性冠状动脉造影检查的患者160例，其中急性冠状动脉综合征（ACS）患者60例，稳定型心绞痛（SAP）患者40例，正常对照组60例。测定各组血浆LP（a）浓度并进行比较分析。结果ACS组和SAP组LP（a）水平显著高于对照组，而ACS组LP（a）水平明显高于SAP组。脂蛋白水平与冠状动脉狭窄程度、狭窄范围呈正相关关系（r2=0．44，P〈0．01）。结论LP（a）与冠脉粥样病变的范围、程度及稳定性相关，对冠心病的诊断和预后判断具有一定意义。     

类风湿性关节炎患者血清免疫炎症相关蛋白的分析及新风胶囊对细胞因子的调节作用

目的 分析类风湿性关节炎(RA)的免疫炎症蛋白表达谱,并探究新风胶囊对其干预作用。方法 采用RayBiotech抗体芯片检测RA患者与健康对照者血清中关键蛋白的差异表达。应用Pearson相关性分析差异蛋白与实验室指标[类风湿因子(RF)、超敏C反应蛋白(hs-CRP)、血沉(ESR)、抗环瓜氨酸肽(ACCP)抗体]的相关性。选取80例RA患者随机分为新风胶囊(XFC)组和来氟米特组(LEF)各40例,治疗4周后,观察两组临床疗效、实验室指标、患者感受评分[焦虑自评量表(SAS)、抑郁自评量表(SDS)、简明健康状况调查问卷表(SF-36)]、差异蛋白的变化。结果 与健康对照者相比,RA组中上调的蛋白有24种,下调的蛋白有9种,而白细胞介素2(IL-2)、IL-5、IL-11、IL-17、肿瘤坏死因子β(TNF-β)、细胞毒性T淋巴细胞相关蛋白4(CTLA4)表达上调,IL-8、程序性死亡蛋白1配体2(PD-L2)、CD86表达下调,其中,差异表达最显著的为IL-11、IL-17、PD-L2。IL-11与hs-CRP(r=0.2412)、ESR呈正相关(r=0.3799), IL-17...     

血清脂蛋白(a)水平及LPA基因SNPrs3798220与冠心病的相关性研究

目的 研究血清脂蛋白（a）[Lp（a）]水平及人载脂蛋白a基因SNP rs3798220（LPA SNP rs3798220）与冠心病的相关性.方法 以200例冠脉造影证实为冠心病的患者为冠心病组,以200名健康者为对照组,采用高分辨熔解曲线分析方法（HRM）分析LPA SNP rs3798220与冠心病的相关性,并测定Lp（a）水平.结果 冠心病组T/C＋C/C型频率、C等位基因频率均高于对照组（P＜0.05）.Logistic回归分析发现,LPA SNP rs3798220 T/C＋ C/C型与冠心病正相关（OR：2.878,95.0％ CI：1.306～6.339,P＜0.05）,Lp（a）水平与冠心病的发病呈正相关（OR：1.068,95.0％ CI：1.041-1.095,P＜0.05）.结论 载旨蛋白a基因SNP rs3798220 T/C＋C/C型可能是冠心病的易感基因型,血清Lp（a）水平可能是冠心病的一个危险因素.     

类风湿性关节炎患者血清IL-6水平及其基因多态性研究

目的: 探讨血清IL-6水平及其基因多态性与类风湿性关节炎(RA)的相关性.方法: 采用酶联免疫吸附法(ELSIA)检测148例RA患者血清IL-6水平,并用序列特异性引物-聚合酶链反应(PCR-SSP)技术检测患者IL-6基因启动子两个位点的等位基因和基因型(IL-6-572C/G、 IL-6-174G/C).与健康对照组(120例)相比较.结果: RA患者血清IL-6水平明显高于对照组(P<0.01),IL-6-174G/C位点CC、 GC与GG基因型分布频率与健康对照组有明显差异(P<0.01),其C等位基因频率高于对照组(P<0.01),IL-6-572C/G位点GG、 GC与CC基因型两组之间比较有统计学意义(P<0.01),其G等位基因频率明显低于健康对照组(P<0.01).结论: RA与患者血清IL-6有关;IL-6-174G/C位点的C等位基因可能是RA发病的独立危险因素,IL-6-572C/G位点的G等位基因-可能有一定保护作用.     

肾炎和肾病综合征患者血清脂蛋白（a）水平的临床意义

肾炎和肾病综合征患者血清脂蛋白（ａ）水平的临床意义程新宪１赵怡生２易忠群１赵惠芳１杨欣国３（１解放军３２３医院中心实验室，西安７１００５４２西安市中心医院３第四军医大学唐都医院心内科）近年研究证实脂蛋白（ａ）［Ｌｐ（ａ）］是动脉粥样硬化性心脑血管疾...     

儿童肾脏病血清脂蛋白(a)水平及临床意义

对 5 0利肾脏病患儿进行了血清脂蛋白 (a) [Lp(a) ]测定。结果发现 :肾病综合征 (NS)患儿在不同病期 (肾病期和缓解期 )Lp(a)水平均高于正常对照组 ,紫癜性肾炎 (肾病型 )Lp(a)亦较正常组为高 ,而肾小球肾炎无论急性期和恢复期与对照组比较差异均无显著意义。提示 :NS患儿即使临床未出现合并症 ,但体内已具备了诱发动脉粥样硬化性心血管病的生物化学基础。建议应做好NS患儿血清Lp(a)的监测 ,必要时给予干预 ,以改善NS患儿的愈后。     

性激素与类风湿性关节炎发生发展的研究进展

性激素是由性腺和肾上腺产生或由其他物质转化而来的类固醇激素。类风湿性关节炎(rheumatoid arthritis,RA)是一种以关节内炎症细胞浸润为特点的自身免疫性疾病,女性RA的发病率比男性高。本文综述性激素在RA发生发展中的作用。首先,介绍RA和性激素的概况,横向比较两性间性激素的差异,分析不同性激素对RA发展的影响;其次,纵向比较因患病导致的性激素水平变化情况及性激素失衡的发生机制;进一步分析与性激素相关的RA治疗方法。     

Effect of low-density lipoprotein buoyant density and cholesterol content on the formation of lipoprotein(a) particles

Lipoprotein(a) [Lp(a)] is a unique lipoprotein which resembles low-density lipoprotein (LDL) both in lipid composition and the presence of apolipoprotein B-100 (apo B-100). Lp(a) is, however, distinguishable from LDL by the presence of an additional glycoprotein apolipoprotein(a) [apo(a)], which is covalently attached to apo B-100 by a single disulfide bond. It is now generally accepted that Lp(a) assembly is a two-step process in which the initial non covalent interaction between apo(a) and apo B-100 is mediated by the weak lysine binding sites present in kringle IV types 6, 7 and 8 of apo(a). In the present study, we have investigated the effect of LDL heterogeneity on Lp(a) assembly in a group of 111 individuals. The three parameters of LDL composition assessed in this study were the cholesterol content, the apo B content, and the relative flotation rate (a measure of LDL buoyancy and thus size). We found no correlation between the size of LDL particles and the extent of Lp(a) formation; a weak negative correlation was observed between cholesterol content of LDL and Lp(a) formation (P=0.042). This may suggest a role for free (i. e., surface-associated) cholesterol in the ability of LDL to form Lp(a) particles. Received: 1 June 2001 / Accepted: 2 July 2001     

Apolipoprotein E phenotype and lipoprotein(a) in familial hypercholesterolaemia implication for lipoprotein(a) metabolism

The mechanisms regulating plasma levels of lipoprotein(a) [Lp(a)] are largely unknown. A two- to three-fold increase in Lp(a) levels in patients with familial hypercholesterolaemia (FH) has implied that LDL receptor activity may be an important factor in determining plasma Lp(a) levels, as it is in determining low-density lipoprotein (LDL) cholesterol concentration. Common apolipoprotein E (apoE) variants also affect plasma LDL cholesterol levels. We therefore examined the effect of the common apoE variants on plasma Lp(a) levels in 149 patients with heterozygous FH. Patients with the apoE₂ allele (n = 11) had significantly higher plasma levels of LDL cholesterol compared to those with a apoE₃E₃ phenotype, while patients with the apoE₄ isoform had similar levels. However, there was a significant effect of the apoE₂ allele in lowering Lp(a) levels, compared to the apoE₃E₃ group. The median Lp(a) concentration in patients possessing an apoE₂ isoform was 13.1 mg/dl below the median, while in those with an apoE₄ allele the median Lp(a) levels were 4.13 mg/dl higher. There was a marked inverse correlation between plasma Lp(a) and LDL cholesterol concentration in the FH patients carrying the apoE₂ allele. Our data imply that difference in Lp(a) levels observed between FH patients with different apoE isoforms does not result from altered clearance of Lp(a) via the LDL receptor pathway, and suggest that apoE mediated hepatic up-take, or conversion, of remnant particles may be determining Lp(a) production rate.Abbreviations apo apoprotein - CHD coronary heart disease - FH familial hypercholesterolaemia - HDL high-density lipoprotein - LDL low-density lipoprotein - Lp(a) lipoprotein(a)     

Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis

Rheumatoid arthritis is characterized by synovial proliferation, neovascularization and leucocyte extravasation leading to joint destruction and functional disability. The blood vessels in the inflamed synovium are highly dysregulated, resulting in poor delivery of oxygen; this, along with the increased metabolic demand of infiltrating immune cells and inflamed resident cells, results in the lack of key nutrients at the site of inflammation. In these adverse conditions synovial cells must adapt to generate sufficient energy to support their proliferation and activation status, and thus switch their cell metabolism from a resting regulatory state to a highly metabolically active state. This alters redox-sensitive signalling pathways and also results in the accumulation of metabolic intermediates which, in turn, can act as signalling molecules that further exacerbate the inflammatory response. The RA synovium is a multi-cellular tissue, and while many cell types interact to promote the inflammatory response, their metabolic requirements differ. Thus, understanding the complex interplay between hypoxia-induced signalling pathways, metabolic pathways and the inflammatory response will provide better insight into the underlying mechanisms of disease pathogenesis.     

Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with hyperthyroidism

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apoB) is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated. High plasma levels of Lp(a) are associated with atherosclerotic diseases. It is therefore of interest to study whether factors other than the apo(a) gene locus are involved in the regulation of Lp(a) concentrations. We measured plasma concentrations of Lp(a) and other lipoproteins and determined apo(a) phenotypes in 31 patients with hyperthyroidism, before and after the patients had become euthyroid by treatment. The mean concentration of LDL cholesterol rose from 2.67 to 3.88 mmol/l (P<0.01), apoB rose from 0.79 to 1.03 g/l (P<0.01), and the median Lp(a) concentration increased from 9.74 to 18.97 mg/dl (P<0.01) on treatment. Lp(a) concentrations were inversely associated to the size of the apo(a) molecule both before (P< 0.01) and after treatment (P<0.01). The increase in Lp(a) was significant patients with high molecular weight apo(a) phenotypes (n = 9; P<0.01) and in patients with low molecular weight apo(a) phenotypes (n=16; P< 0.01), but not in those with apo(a) null types (n = 6; P = 0.5). The low levels LDL cholesterol and apoB in untreated hyperthyroidism may result from increased LDL receptor activity. The increase in Lp(a) levels were not correlated with the increase in LDL cholesterol or apoB. Most other clinical evidence indicates that the LDL receptor is not important in Lp(a) catabolism, and we suggest that the low Lp(a) levels seen in thyroid hormone excess are caused by an inhibition of Lp(a) synthesis.Abbreviations Lp(a) lipoprotein(a) - apo(a) apolipoprotein(a) - apoB apolipoprotein B-100 - LDL low-density lipoprotein - HDL high-density lipoprotein - TG triglycerides - T ₄ thyroxine - T ₃ triiodothyronine - TSH thyrotropin     

Ischemic stroke in a young adult with extremely elevated lipoprotein(a): A case report and review of literature

Lipoprotein(a) [Lp(a)] is an apolipoprotein(a) molecule bound to 1 apolipoprotein B-100. Elevated levels of Lp(a) are thought to be an independent risk factor for atherosclerosis and to promote thrombosis through incompletely understood mechanisms. We report a 34-year-old man with an ischemic stroke in the setting of an extremely high Lp(a) level—212 mg/dL. He developed severe carotid artery stenosis over a 6-year period and had thrombus formation post-carotid endarterectomy. To our knowledge, this case is unique because the Lp(a) is the highest reported level in a patient without renal disease. Moreover, this is the first reported case of the youngest individual with a stroke presumably related to development of carotid plaque over a 6-year period. The thrombotic complication after endarterectomy may have been related to the prothrombotic properties of Lp(a). Of note, the Lp(a) level did not respond to atorvastatin but did decrease 15% after aspirin 325 mg was added although his Lp(a) levels were variable, and it is not clear that this was cause and effect. This case highlights the need to better understand the relation between Lp(a) and vascular disease and the need to screen family members for elevated Lp(a). We also review treatment options to lower Lp(a) and ongoing clinical trials of newer lipid-lowering drugs that can also lower Lp(a).     

Correlation of P-selectin and lipoprotein(a), and other lipid parameters in preeclampsia

Preeclampsia is a pregnancy specific disorder and is thought to be associated with generalized endothelial dysfunction. P-selectin, an adhesion molecule, mediates the interaction of monocytes, platelets, and endothelial cells. Increased P-selectin levels and altered lipid and lipoprotein metabolism were reported in preeclampsia and during pregnancy. In order to investigate the relationship between serum P-selectin and lipoprotein(a), and other lipid parameters, 28 preeclampsia [13 severe (group I) and 15 mild preeclampsia (group II), 15 healthy pregnant (group III) and 20 non-pregnant (group IV)] women were investigated. Serum P-selectin, lipoprotein(a), total cholesterol, triglyceride, and high density lipoprotein cholesterol were measured and low-density lipoprotein cholesterol was derived. Serum P-selectin concentrations were consistently and significantly higher in the severe preeclampsia group than in the mild preeclampsia, healthy pregnancy, and non-pregnant control groups (P<0.0001, for all). The mild preeclampsia group also had increased serum P-selectin concentrations compared with the healthy pregnancy group and non-pregnant controls (P<0.05 and P<0.0001, respectively). Serum P-selectin and lipoprotein(a) levels revealed a significant and linear increase with the severity of preeclampsia. There were also significant (in groups I and II) and borderline (in groups III and IV) correlations between P-selectin and total cholesterol. The present study suggests that P-selectin may be an additional risk marker for preeclampsia, and may be useful in distinguishing women with mild and severe preeclampsia and normal pregnancy. Received: 9 November 2001 / Accepted: 6 February 2002     

Increased levels of lipoprotein(a) in non-smoking aortic dissection patients

OBJECTIVES: To investigate lipoprotein(a) (Lp(a)) serum levels in patients with aortic dissection and the influence of smoking on the level of Lp(a) in aortic dissection patients. METHODS: An age-and sex-matched case-control study was conducted. Lp(a) levels in patients with aortic dissection (n = 52) and healthy subjects (n = 104) were studied. The strength of associations between Lp(a) serum levels and aortic dissection was assessed by means of multivariate logistic regression analysis. RESULTS: Patients with aortic dissection had significantly higher Lp(a) serum levels (median, 17.6 mg/dl; range, 6.4-88.7 mg/dl) compared to healthy individuals (median, 12.4 mg/dl; range, 4.9-26.4 mg/dl) (p = 0.005). The Lp(a) concentration in non-smoking patients with aortic dissection (median, 19.1 mg/dl, range, 10.5-88.7 mg/dl) significantly surpassed that of the smoking patients with aortic dissection of comparable age (median, 10.7 mg/dl; range, 6.4-22.1 mg/dl) (p < 0.0001). Multivariate analysis confirmed an independent association between Lp(a) and aortic dissection in the non-smoking population (p = 0.001). CONCLUSIONS: Serum Lp(a) level is significantly elevated in non-smoking patients with aortic dissection independently of other cardiovascular risk factors. Therefore, determination of Lp(a) levels may be important in identifying subjects at risk of aortic dissection among nonsmokers.     

Biomolecular features of inflammation in obese rheumatoid arthritis patients: management considerations

Adipose tissue is an active organ playing a role not only in metabolism but also in immune and inflammatory processes, releasing several pro-inflammatory mediators. This can explain the possible association between obesity and rheumatoid arthritis (RA) and its role in the progression of the disease. Adipose and synovial tissues share common histological features of local inflammation in terms of activation of target tissues infiltrating cells (i.e. myeloid cells). Among the so-called adipocytokines, PEDF and Chemerin orchestrate the cellular cross-talk between adipose and myeloid cells, being possible biomarkers to monitor the effect of weight loss or the decrease of adipose tissue in patients with RA. Moreover, dietary intervention has been demonstrated to reduce Chemerin as well as IL-6 and MCP-1 expression. Finally, epigenetic regulators such as micro-RNAs (i.e. miR-155) are key regulators of myeloid cells activation in RA and obesity as well as in adipocytes. In this review, we will summarize the biological link between obesity/overweight state and RA focusing on pathophysiological mechanisms, consequences and management considerations.     

Triglyceride and lipoprotein (a) are markers of coronary artery disease severity among postmenopausal women

Objective: After menopause, some women manifest coronary artery disease (CAD) with highly variable angiographic severity. For these women, postmenopausal appearing of some CAD risk factors may have differently influenced the CAD risk and severity. In this study, we attempt to unravel differences in the frequency or intensity of CAD risk factors among postmenopausal women with different angiographic severity. Methods: We studied 182 postmenopausal women (64±6 years) who underwent coronary angiography to investigate thoracic pain. Subjects with no detectable coronary lesions at angiography were recruited to the non-obstructive group and patients with CAD were grouped in one-vessel or multi-vessel groups. We compared clinical variables as the body mass index (BMI), age at menopause, age, hypertension, diabetes and cigarette smoking, and lipid measurements as plasma levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein (apo) A1, apo B and lipoprotein(a) (Lp(a)). Results: Comparing to the non-obstructive group, Lp(a) was twofold higher in the one-vessel group and threefold higher in the multi-vessel group and triglycerides were 34% higher in the one-vessel group and 50% higher in the multi-vessel group. No further difference was found among the three groups. After multivariate logistic regression analysis, triglyceride (odds ratio: 1.01; P=0.0013) and Lp(a) (odds ratio: 1.006; P<0.0001) were independently indicative of the presence of obstructive CAD. Conclusion: We found that both Lp(a) and triglycerides constitute useful markers of CAD severity among postmenopausal women.     

Site‐specific absence of microfibrillar‐associated protein 4 (MFAP4) from the internal elastic membrane of arterioles in the rheumatoid arthritis synovial membrane: an immunohistochemical study in patients with advanced rheumatoid arthritis versus osteoarthritis

Microfibrillar‐associated protein 4 (MFAP4) is a non‐structural matrix protein with cell regulatory activities and a potential as seromarker for fibrosis. We aimed to study the occurrence of MFAP4 in the synovial membrane from patients with rheumatoid arthritis (RA) vs osteoarthritis (OA). Formaldehyde‐fixed synovial tissue sections, from patients with RA (N = 6) and OA (N = 6) undergoing total hip arthroplasty, were deparaffinized and immunostained with monoclonal antibodies against MFAP4. Elastin was detected using ElastiKit. MFAP4 in serum (sMFAP4) and synovial fluid was measured by an immunoassay. MFAP4 was present in synovial biopsies from both RA and OA patients, particularly prominent in deep arterioles where it colocalized with elastin. Notably however, MFAP4 was absent from the internal elastic lamina in RA arterioles irrespective of disease duration and synovitis activity, while present although with irregular staining patterns in OA specimens. sMFAP4 was increased in RA and OA serum vs healthy controls: median (interquartile range) 29.8 (25.3–39.1) and 25.5 U/L (18.1–43.3) vs 17.7 U/L (13.7–21.2), p = 0.006 and p = 0.02, respectively The concentration of synovial fluid was lower than in serum in both RA and OA. These findings may suggest that MFAP4 is involved in adaptive vessel wall remodeling associated with chronic joint disease.