抵抗素与炎症、动脉粥样硬化

大量研究证实,胰岛素抵抗代谢综合征和动脉粥样硬化(AS)存在着密切联系,脂肪细胞是非常重要的内分泌器官〔1〕,释放大量的生物活性分子,不仅在胰岛素抵抗(IR)的发病有显著的作用,而且还是重要的血管活性因子,可能是代谢综合症病人心血管疾病的重要基础机制。抵抗素(resistin),这一新近发现的脂肪细胞因子,最初被认为联系着肥胖和IR,近几年研究表明抵抗素与炎症及AS的发生发展也存在一定联系。1抵抗素的功能与结构抵抗素是由Steppan等〔2〕于2001年在研究一类抗糖尿病新药———胰岛素增敏剂噻唑烷二酮衍生物(TZDs)的作用机制时,在小鼠…     

抵抗素与动脉粥样硬化

抵抗素最初被认为是联系肥胖、胰岛素抵抗和2型糖尿病的新型脂肪细胞因子。但随后的研究发现抵抗素在人体主要参与炎症和免疫反应。动脉粥样硬化是一种慢性炎症性过程，体外研究提示抵抗素可能参与动脉粥样硬化的发生发展。本文就抵抗素参与动脉粥样硬化的具体机制作一综述。     

抵抗素的研究进展

抵抗素样分子家族(RELMs)是一组由105～117个氨基酸残基组成的蛋白质家族,均含有3个结构域氨基端信号肽、中间可变区、相对保守的富含半胱氨酸的羧基末端序列,该家族的蛋白与家族之外的其他蛋白缺乏明显的同源性[1].现将抵抗素研究的新进展作一综述.     

血浆抵抗素与冠心病的相关性研究

目的:观察不同类型心绞痛患者血浆抵抗素水平的变化,以及血浆抵抗素水平与代谢指标、炎症指标等之间的相关性。方法:根据造影结果及临床表现,将114例研究对象分为不稳定型心绞痛(UAP)组(46例)、稳定型心绞痛(SAP)组(37例)和对照组(31例)。收集患者一般临床资料及生化指标;免疫比浊法检测高敏C反应蛋白(hs-CRP)水平;放免法检测血清胰岛素水平;ELISA法检测血浆抵抗素水平。结果:UAP组血浆抵抗素水平[12.09(8.40,18.08)ng/ml]显著高于SAP组[9.04(7.09,11.44]ng/ml,P<0.05],及对照组[8.71(6.58,11.56)μg/L,P<0.01]。抵抗素水平分别与年龄(R2=0.06,P<0.01)、白细胞计数(R2=0.05,P<0.05)以及hs-CRP(R2=0.05,P<0.05)独立正相关。结论:抵抗素可能通过影响系统的炎症反应参与冠心病的发生发展。     

032 抵抗素为人类致动脉粥样硬化相关炎症标记物之一

抵抗素（Resistin）属一种血浆蛋白质，并能诱发啮齿类动物体内产生胰岛素抵抗。晚近报道发现，在人类和啮齿类动物伴肥胖和胰岛素抵抗者中循环内抵抗素水平明显升高。在啮齿类动物中，抵抗素主要由脂肪细胞和巨噬细胞产生，推测在人类亦然。综合脂肪细胞和巨噬细胞功能提示，抵抗素可提供与人类肥胖、炎症和致动脉粥样硬化三者间相关联的独特的内在联系。本文拟就抵抗素与人类致动脉粥样硬化相关炎症间关系进行了分析。     

炎症与动脉粥样硬化

炎症的介导在动脉粥样硬化(AS)的发病机理中从白细胞聚集到最后的易损动脉硬化斑块的破裂，扮演了一个重要的角色。早期AS的产生与单核细胞黏附到血管内皮细胞和黏附的范围有关。单核细胞分化和泡沫细胞形成，并逐步形成脂质条纹，均与炎症有关。炎症细胞的增多和血管平滑肌细胞的增生导致动脉粥样损伤的更进一步发展，越来越多的证据显示炎症的过程与AS的每一个阶段有着密切的关系。     

炎症、动脉粥样硬化与胰岛素

动脉粥样硬化是一个炎症反应的过程。内皮损伤后,产生黏附因子,吸附大量的单核细胞,激活核因子(NF)κB,并导致一系列超氧化自由基的产生,促进趋化因子等炎症因子产生,从而引起一系列继发反应。胰岛素具有扩张血管、抗血小板聚集、抗炎、抗动脉粥样硬化及保护心脏的作用。总之,胰岛素具有抑制炎症反应的重要作用,从而可以防止动脉粥样硬化的发生、发展。     

抵抗素样分子α与动脉粥样硬化关系的研究进展

一、抵抗素样分子α概况 1．抵抗素样分子α的发现及命名：Steppan等于2000年首次在卵清蛋白诱导的鼠肺部炎症模型中,用十二烷基硫酸钠一丙烯酰胺凝胶分析支气管肺泡灌洗液时发现的一个暗带区域.     

感染、炎症与动脉粥样硬化

近年来的大量研究表明,感染、炎症与动脉粥样硬化和冠心病的发生与发展具有一定的相关性,慢性潜在性的感染诱导多种细胞因子的产生、粘附分子的表达,可能是刺激动脉粥样硬化炎病反应的始动因子之一。     

抵抗素的研究进展

抵抗素是存在于血浆中的富含半胱氨酸的分泌性蛋白。新近研究表明,抵抗素可作用于脂肪、肝脏、骨骼肌等胰岛素靶器官,通过影响胰岛素信号转导途径及代谢相关酶的转录影响糖、脂代谢,参与机体的能量调节。人抵抗素主要在外周血单核细胞中表达。抵抗素可作用于血管内皮细胞及平滑肌细胞影响其功能。临床研究显示,抵抗素与多个炎症标志相关,与动脉粥样硬化的病变范围关系密切,提示抵抗素可能在动脉粥样硬化的发病机制中发挥作用。     

抵抗素与炎性反应关系的研究进展

血浆抵抗素主要来源于炎性反应处的单核细胞和巨噬细胞.它与炎性反应及许多炎性反应性疾病的活动性密切相关,与炎性标记物形成网络,通过Ca2+/核因子(NF)-κB依赖途径发挥促炎及促胰岛素抵抗作用.     

血清抵抗素水平与动脉粥样硬化的相关性研究

目的探讨血清抵抗素与动脉粥样硬化的关系及其可能在糖尿病大血管并发症中所起的作用。方法病例选自2004年9月至2005年3月北京军区总医院的行冠状动脉造影的患者共88例,分为单纯冠心病组、糖尿病合并冠心病组、单纯糖尿病组以及正常对照组。受试者空腹采血,行生化检查及血清抵抗素、高敏C反应蛋白(hs-CRP)、可溶性肿瘤坏死因子受体2(sTNF-R2)的测定。结果各组患者血清抵抗素以及hs-CRP、sTNF-R2均高于正常对照组(P<0·05);抵抗素与sTNF-R2呈正相关(r=0·24,P=0·025),而与hs-CRP无显著相关性(P=0·613);多元回归分析显示,性别(b=0·194,P=0·029)及冠状动脉病变支数(b=0·155,P=0·001)是影响血清抵抗素水平的因素;随着冠脉病变支数的增加,血清抵抗素呈增高的趋势(P=0·004)。结论冠心病患者,特别是糖尿病合并冠心病患者,血清抵抗素水平增高;冠脉病变支数是影响血清抵抗素的重要因素;血清抵抗素水平与炎症标志呈正相关,提示抵抗素可能作为炎症因子在动脉粥样硬化以及糖尿病大血管并发症的发病机制中发挥作用。     

血清抵抗素水平与动脉粥样硬化的相关性研究

目的 探讨血清抵抗素与动脉粥样硬化的关系及其可能在糖尿病大血管并发症中所起的作用。方法 病例选自2004年9月至2005年3月北京军区总医院的行冠状动脉造影的患者共88例，分为单纯冠心痛组、糖尿病合并冠心痛组、单纯糖尿病组以及正常对照组。受试者空腹采血，行生化检查及血清抵抗素、高敏C反应蛋白（hs—CRP）、可溶性肿瘤坏死因子受体2（sTNF—R2）的测定。结果 各组患者血清抵抗素以及hs—CRP、sTNF—R2均高于正常对照组（P〈0．05）；抵抗素与sTNF—R2呈正相关（r=0．24，P=0．025），而与hs—CRP无显著相关性（P=0．613）；多元回归分析显示，性别（b=0．194，P=0．029）及冠状动脉痛变支数（b=0．155，P=0．001）是影响血清抵抗素水平的因素；随着冠脉病变支数的增加，血清抵抗素呈增高的趋势（P=0．004）。结论 冠心病患者，特别是糖尿病合并冠心痛患者，血清抵抗素水平增高；冠脉病变支数是影响血清抵抗素的重要因素；血清抵抗素水平与炎症标志呈正相关，提示抵抗素可能作为炎症因子在动脉粥样硬化以及糖尿病大血管并发症的发病机制中发挥作用。     

辛伐他汀对C-反应蛋白诱导的抵抗素表达的实验研究

目的:探讨辛伐他汀对C-反应蛋白CRP诱导的人外周血单核细胞抵抗素mRNA和蛋白表达的影响。方法:分离培养人外周血单核细胞,分别与不同浓度的辛伐他汀(0.1,1,10μmmol/L)预孵育2 h,再与25μg/mL CRP共同培养24 h,分别用实时定量PCR和ELISA方法检测单核细胞抵抗素mRNA表达及细胞培养液中抵抗素的浓度。结果:辛伐他汀呈剂量依赖性地抑制CRP诱导的抵抗素mRNA和蛋白表达。结论:辛伐他汀可显著抑制CRP诱导的抵抗素的表达,提示CRP和抵抗素可能参与动脉粥样硬化(As)的进展,他汀类药物可能通过调节CRP诱导的抵抗素过度表达发挥其抗As作用。     

Increased level of resistin predicts development of atrial fibrillation

BackgroundResistin is a peptide hormone that is secreted from lipid cells and is linked to type-2 diabetes, obesity, and inflammation. Being an important adipocytokine, resistin was proven to play an important role in cardiovascular disease. We compared resistin levels in patients with and without atrial fibrillation (AF) to demonstrate the relationship between plasma resistin levels and AF.MethodOne hundred patients with AF and 58 control patients who were matched in terms of age, gender, and risk factors were included in the trial. Their clinical risk factors, biometric measurements, echocardiographic work up, biochemical parameters including resistin and high-sensitivity C-reactive protein (hs-CRP) levels were compared.ResultsIn patients with AF, plasma resistin levels (7.34 ± 1.63 ng/mL vs 6.67 ± 1.14 ng/mL; p = 0.003) and hs-CRP levels (3.01 ± 1.54 mg/L vs 2.16 ± 1.28 mg/L; p = 0.001) were higher than control group. In subgroup analysis, resistin levels were significantly higher in patients with paroxysmal (7.59 ± 1.57 ng/mL; p = 0.032) and persistent AF (7.73 ± 1.60 ng/mL; p = 0.006), but not in patients with permanent AF subgroups (6.86 ± 1.61 ng/mL; p = 0.92) compared to controls. However, hs-CRP levels were significantly higher only in permanent AF patients compared to control group (3.26 ± 1.46 mg/L vs 2.16 ± 1.28 mg/L; p = 0.02). In multivariate regression analysis using model adjusted for age, gender, body mas index, hypertension, diabetes mellitus, and creatinine levels, plasma resistin levels [odds ratio (OR): 1.30; 95% confidence interval (CI): 1.01–1.70; p = 0.04] and hs-CRP levels (OR: 1.44; 95% CI: 1.12–1.86; p = 0.004) were the only independent predictors of AF.ConclusionThe elevated levels of plasma resistin were related to paroxysmal AF group and persistent AF group, but not to permanent AF group.     

抵抗素参与血管内皮细胞功能障碍的研究进展

抵抗素是脂肪细胞分泌的一种多肽类激素,早有研究证明抵抗素通过影响胰岛素信号转导参与了胰岛素抵抗,与2型糖尿病的发生发展密切相关.越来越多研究表明抵抗素可以促进肿瘤坏死因子α、白细胞介素6等炎症标志物的表达,诱导血管炎症反应的发生,从而损伤血管内皮细胞并影响其功能.内皮细胞功能异常又是动脉粥样硬化及糖尿病血管并发症病理过程的始动环节,提示抵抗素可能在心血管疾病的发生发展中起重要作用.本文就有关抵抗素参与血管内皮细胞功能障碍的研究进展作一综述.     

Serum resistin,insulin resistance and carotid intima-media thickness as an indication of subclinical atherosclerosis in systemic lupus erythematosus patients

Aim of the workTo evaluate resistin level in systemic lupus erythematosus (SLE) patients and to assess the relationship with insulin resistance, disease characteristics, inflammatory markers and carotid intima-media thickness (CIMT) as a marker of subclinical atherosclerosis.Patients and methodsThirty adult SLE patients and twenty age and sex-matched control were enrolled. All patients were subjected to history taking, clinical examination and assessment of anthropometric measurements. Laboratory investigations included serum resistin, measures of insulin resistance, highly sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) and lipid profile. Carotid duplex was performed for measurement of CIMT. SLE disease activity index (SLEDAI-2k) and damage index were evaluated.ResultsThe 30 patients were 23 (76.7%) females and 7 (23.3%) males (F:M 3.3:1) with a mean age of 30.9 ± 7.9 years. The disease duration was 4.8 ± 1.8 years. The mean serum resistin in patients was 7.7 ± 2.9 ng/dl and in control was 8.5 ± 5.1 ng/dl (p = 0.8). The ESR and hs-CRP were significantly increased (p < 0.001) and the high-density lipoprotein (HDL) decreased (p < 0.001). The mean CIMT was significantly increased in cases (0.62 ± 0.16 mm) compared to control (0.51 ± 0.11 mm)(p = 0.006). Serum resistin significantly correlated with hs-CRP, HDL and anti-nuclear antibody (p = 0.027, p < 0.001,p = 0.013 respectively). There was no significant correlation between resistin and markers of insulin resistance, SLEDAI-2 k and CIMT.ConclusionResistin expression in the serum of patients with SLE was not significantly higher than controls. Although resistin was correlated with two cardiovascular risk factors (HDL-C, hs-CRP), it did not correlate significantly with insulin resistance, disease activity, damage index and CIMT in SLE patients.     

The prevalence of inflammation in carotid atherosclerosis: analysis with fluorodeoxyglucose-positron emission tomography.

AIMS: There is increasing evidence that (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging can be useful for non-invasive measurement of atherosclerotic plaque inflammation in humans. However, it is unknown how often atherosclerosis has inflammation in humans. Thus, we examined the prevalence of inflammation in documented carotid atherosclerosis using FDG-PET imaging. METHODS AND RESULTS: FDG-PET imaging was performed in 100 consecutive patients who underwent carotid artery ultrasonography (CA-US) for screening of carotid atherosclerosis. Carotid atherosclerosis was considered when patients had the plaque score >or=5 and/or the focal thickening of the maximum intima-media complex >or=2 mm (localized plaque) by CA-US. The inflammation of carotid atherosclerosis was quantified by measuring the standardized uptake value (SUV) of FDG of the carotid artery. Inflammation was defined as present if the SUV score was >or=1.60 (>or=1 x standard deviation above the average). FDG-PET imaging revealed inflammation in 12 of 41 (29%) patients having carotid atherosclerosis, whereas in 6 of 59 (10%) patients not having carotid atherosclerosis (P < 0.01). In patients with documented atherosclerosis by CA-US, body mass index, waist circumference, and the number of localized plaques were greater in a subset with inflammation than in a subset without. CONCLUSION: Inflammation was visualized by FDG-PET imaging in approximately 30% of patients with documented carotid atherosclerosis.     

The role of inflammation in the association between overall and visceral adiposity and subclinical atherosclerosis

Background and aimsInflammation may underlie the association between obesity, atherosclerosis and cardiovascular disease. We investigated to what extent markers of inflammation mediate associations between overall and visceral body fat and subclinical atherosclerosis.Methods and resultsIn this cross-sectional analysis of the Netherlands Epidemiology of Obesity study we estimated total body fat (TBF) by bio-impedance analysis, carotid artery intima media thickness (cIMT) by ultrasound, C-reactive protein (hs-CRP) and glycoprotein acetyls (GlycA) concentrations in fasting blood samples (n = 5627), and visceral adipose tissue (VAT) by magnetic resonance imaging (n = 2247). We examined associations between TBF and VAT, and cIMT using linear regression, adjusted for potential confounding factors, and for mediators: cardiometabolic risk factors (blood pressure, glucose and low-density lipoprotein cholesterol), and inflammation using CRP and GlycA as proxies.Mean (SD) cIMT was 615 (90) μm. Per SD of TBF (8%), cIMT was 19 μm larger (95% confidence interval, CI: 10, 28). This association was 17 μm (95% CI: 8, 27) after adjustment for cardiometabolic risk factors, and did not change after adjustment for markers of inflammation. Per SD (56 cm²) VAT, cIMT was 9 μm larger (95% CI: 2, 16) which changed to 5 μm (95% CI: −3, 12) after adjustment for cardiometabolic risk factors, and did not change after adjustment for inflammatory markers.ConclusionOur results suggest that associations between measures of overall and visceral body fat and subclinical atherosclerosis are not mediated by inflammation as measured by CRP and GlycA. Obesity may exert cardiovascular risk via other markers of systemic inflammation.