趋化因子CX3C受体1基因rs3732378多态性与急性冠状动脉综合征的相关性

目的探讨趋化因子CX3C受体1(CX3CR1)基因rs3732378单核苷酸多态性与急性冠状动脉综合征(ACS)的相关性。方法连续收集中国北方汉族人群951例,其中男性520例,女性431例,年龄35~75岁。根据冠状动脉造影(CAG)结果分为2组:(1)病例组(n=512):ACS患者;(2)对照组(n=439):非冠心病患者。病例组根据CAG检查血管病变支数分为3个亚组。采用测序法测定CX3CR1基因rs3732378单核苷酸多态位点的基因型。用多因素Logistic回归分析CX3CR1基因rs3732378多态性与ACS发病风险的关系。应用酶联免疫吸附法检测血浆中趋化因子CX3C配体1(CX3CL1)表达水平。结果两组CX3CR1基因rs3732378的基因型及等位基因的分布频率无显著性差异(P0.05)。rs3732378多态位点与ACS发病风险的总体和分层分析结果表明,CX3CR1基因rs3732378多态位点的3种基因型TT、TC和CC均不能增加ACS的发病风险(P0.05)。亚组分析显示,rs3732378多态位点的基因型和等位基因与冠状动脉血管病变支数无相关性(χ2=0.135,P=0.998;χ2=0.026,P=0.987)。病例组和对照组血浆中CX3CL1表达水平在rs3732378三种基因型无差异(P0.05)。结论 CX3CR1基因rs3732378多态位点不是ACS的易感基因,rs3732378多态性没有增加中国北方汉族人群ACS的风险。     

缺血性脑血管病患者趋化因子受体CX3CR1基因V2491多态性的研究

目的 探讨缺血性脑血管病(ICVD)患者趋化因子受体CX3CR1基因V2491的多态性及其频率.方法 采用聚合酶链反应和限制性片段长度多态性方法检测ICVD患者(脑梗死、腔隙性脑梗死、短暂性脑缺血发作)及健康对照者的CX3CR1基因V2491的多态性及频率.结果 对照组CX3CR1基因V2491只有ⅤⅤ和Ⅵ基因型,ICVD组有ⅤⅤ、Ⅵ和Ⅱ3种基因型;ICVD组Ⅰ等位基因频率明显高于对照组(P<0.01);CX3CR1基因型及Ⅰ等位基因频率在不同类型ICVD患者之间无统计学差异.结论 CX3CR1基因V2491多态性可能与ICVD有关.     

CX3CL1/CX3CR1在脑缺血中的作用及其机制

CX3CL1亦称分形趋化因子,是趋化因子CX3C亚类中的唯一成员,通过与其特异性受体CX3CR1结合,在多种中枢神经系统疾病和缺血性脑血管病中发挥重要作用。近年来,大量研究对CX3CL1/CX3CR1的具体作用和相关分子机制进行了探讨。本文就CX3CL1/CX3CR1在缺血性脑血管病中的作用和相关分子机制进行综述,旨在...     

Fractalkine及其受体CX3CR1与冠心病

趋化因子fractalkine被炎症内皮细胞表达，与受体CX3CR1结合通过黏附和趋化作用、参与免疫及细胞间信息转导以及CX3CR1基因的多态性等多种途径影响动脉粥样硬化的发生和发展。通过对fractalkine蛋白及其受体CX3CR1 V249／I249基因水平的检测以及其作用机制的干预，可能成为冠状动脉粥样硬化性心脏病早期诊断和防治的新途径。     

缺血性脑血管病患者趋化因子受体CX3CR1基因V249I多态性的研究

目的探讨缺血性脑血管病（ICVD）患者趋化因子受体CX3CR1基因V249I的多态性及其频率。方法采用聚合酶链反应和限制性片段长度多态性方法检测ICVD患者（脑梗死、腔隙性脑梗死、短暂性脑缺血发作）及健康对照者的CX3CR1基因V249I的多态性及频率。结果对照组CX3CR1基因V249I只有VV和Ⅵ基因型，ICVD组有VV、VI和Ⅱ3种基因型；ICVD组I等位基因频率明显高于对照组（P〈0．01）；CX3CR1基因型及I等位基因频率在不同类型ICVD患者之间无统计学差异。结论CX3CR1基因V249I多态性可能与ICVD有关。     

趋化因子CX3C配体1在原发性干燥综合征合并间质性肺疾病中的临床意义

目的探讨趋化因子CX3C配体1(CX3CL1)在pSS合并间质性肺疾病(ILD)中的临床意义。方法纳入2019年12月至2020年12月桂林医学院附属医院风湿免疫科就诊的pSS患者共103例[合并ILD 42例(pSS-ILD组), 非ILD 61例(pSS组)], 桂林医学院附属医院健康体检中心健康体检者46名(健康对照组);收集入组患者的基本资料、临床表现、临床指标、肺功能、肺高分辨率CT(HRCT)及血清标本;ELISA法检测CX3CL1、涎液化糖链抗原-6(KL-6)在3组血清中的水平, 分析CX3CL1与pSS-ILD和pSS患者的临床相关指标的相关性。采用独立样本t检验。Kruskal-WallisH检验、Pearson相关、Logistic回归分析方法进行统计学分析。结果①CX3CL1、KL-6在pSS-ILD组比pSS组、健康对照组高[CX3CL1:9.08(3.97, 30.56)ng/ml、8.12(6.16, 8.89)ng/ml与7.09(5.86, 9.07)ng/ml, H=3.53, P=0.019;KL-6:19.08(8.05, 24.72)mU/ml...     

CX3CL1/CX3CR1轴在HIV感染者动脉粥样硬化性心脏病中的作用北大核心CSCD

动脉粥样硬化性心脏病目前是HIV/AIDS患者死亡的主要原因之一,也是HIV/AIDS患者慢病管理的重要一环。然而,HIV/AIDS患者动脉粥样硬化性心脏病的发生机制仍不完全清楚。研究表明,慢性持续性炎症是HIV/AIDS患者心血管疾病发生的主要诱因。CX3CL1/CX3CR1是重要的炎症性趋化因子,HIV/AIDS患者中CX3CL1/CX3CR1的表达上调,可通过细胞趋化作用、炎性反应等参与动脉粥样硬化(AS)的形成。因此,了解CX3CL1/CX3CR1在HIV/AIDS患者动脉粥样硬化过程中的作用机制有助于研发新的干预措施,延缓甚至预防HIV/AIDS患者动脉粥样硬化性心脏病的发生发展。本文将从CX3CL1/CX3CR1与动脉粥样硬化的关系,CX3CL1/CX3CR1在HIV/AIDS患者动脉粥样硬化性心脏病中的作用机制等方面进行综述。     

趋化因子CX3C-Fractalkine与肺动脉高压

趋化因子CX3C Fractalkine具有不同于其它趋化因子的特性 ,参与了细胞生长调节、血管生成、细胞间的黏附、免疫炎症反应等多种生物学过程。CX3C Fractalkine在肺动脉高压发病中发挥一定的作用。     

趋化因子CX3C-Fractalkine与肺动脉高压

趋化因子CX3C-Fractalkine具有不同于其它趋化因子的特性，参与了细胞生长调节、血管生成、细胞间的黏附、免疫炎症反应等多种生物学过程。CX3C-Fractalkine在肺动脉高压发病中发挥一定的作用。     

Association between polymorphism in the chemokine receptor CX3CR1 and coronary vascular endothelial dysfunction and atherosclerosis

Fractalkine, a chemokine expressed by inflamed endothelium, induces leukocyte adhesion and migration via the receptor CX3CR1, and the CX3CR1 polymorphism V249I affects receptor expression and function. Here we show that this polymorphism is an independent risk factor for atherosclerotic coronary artery disease (CAD). Genotyping of the CX3CR1-V249I polymorphism was performed in a cohort of 339 white individuals who underwent cardiac catheterization (n=197 with and n=142 without CAD, respectively). In 203 patients, intracoronary acetylcholine 15 microg/min) and sodium nitroprusside (20 microg/min) were administered to test endothelium-dependent and -independent coronary vascular function, respectively. Change in coronary vascular resistance (DeltaCVR) was measured as an index of microvascular dilation. An association was observed between presence of the CX3CR1 I249 allele and reduced prevalence of CAD, independent of established CAD risk factors (odds ratio=0.54 [95% confidence interval, 0.30 to 0.96], P=0.03). Angiographic severity of CAD was also lower in these subjects (P=0.01). Furthermore, endothelium-dependent vasodilation was greater in these individuals compared with individuals homozygous for the CX3CR1-V249 allele (DeltaCVR during acetylcholine = -46+/-3% versus -36+/-3%, respectively, P=0.02), whereas DeltaCVR with sodium nitroprusside was similar in both groups (-55+/-2% versus -53+/-2%, P=0.45). The association between CX3CR1 genotype and endothelial function was independent of established risk factors and presence of CAD by multivariate analysis (P=0.02). Thus, the CX3CR1 I249 allele is associated with decreased risk of CAD and improved endothelium-dependent vasodilation. This suggests that CX3CR1 may be involved in the pathogenesis of CAD.     

Angiotensin II up-regulates CX3CR1 expression in THP-1 monocytes: impact on vascular inflammation and atherogenesis

The potential regulatory effect of angiotensins on circulating mononuclear cell activation and migration has not yet been thoroughly evaluated. Using flow cytometry we assessed the possible effect of angiotensin I and II on the expression of CX3CR1 and a single representative of each major chemokine family (CCR5 and CXCR4) in THP-1 monocytes, Jurcat T lymphocytes and primary monocytes—isolated from healthy donors. Fluorescence intensity and the rate of chemokine-positive cells was measured in naïve cells and cells treated with angiotensin I and II. Neither angiotensin I nor angiotensin II exhibited any effect on fluorescence intensity and the rate of CX3CR1-, CCR5- and CXCR4-positive cells in primary peripheral blood mononuclear cells and Jurkat T cells. However, angiotensin II significantly increased the rate of CX3CR1-positive THP-1 cells. This effect was not attenuated by the pre-incubation of THP-1 cells with the AT-1 receptor blocker losartan, suggesting that this was not an AT-1-mediated effect. Angiotensin I and II had no effect on fluorescence intensity and the rate of CCR5- and CXCR4-positive THP-1 cells. In conclusion, angiotensin II increases the rate of CX3CR1-positive THP-1 cells. By extrapolating this in vitro observation to disease mechanisms, we speculate that angiotensin II induces up-regulation of CX3CR1 and promotes firm adhesion of circulation CX3CR1-positive monocytes on CX3CL1 expressing endothelial cells inducing vascular inflammation and atherogenesis.     

Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis

BACKGROUND: Fractalkine expressed on endothelial cells mediates activation and adhesion of leucocytes expressing its receptor, CX(3)CR1. Soluble fractalkine exhibits chemotactic activity for leucocytes expressing CX(3)CR1. OBJECTIVE: To determine the role of fractalkine and its receptor in systemic sclerosis (SSc) by assessing their expression levels in patients with this disease. METHODS: The expression of fractalkine and CX(3)CR1 in the skin and lung tissues was immunohistochemically examined. Circulating soluble fractalkine levels were examined by enzyme linked immunosorbent assay (ELISA). Blood samples from patients with SSc were stained for CX(3)CR1 with flow cytometric analysis. RESULTS: CX(3)CR1 levels on peripheral monocytes/macrophages and T cells were found to be raised in patients with diffuse cutaneous SSc. The numbers of cells expressing CX(3)CR1, including monocytes/macrophages, were increased in the lesional skin and lung tissues from patients with diffuse cutaneous SSc. Fractalkine was strongly expressed on endothelial cells in the affected skin and lung tissues. Soluble fractalkine levels were significantly raised in sera and were associated with raised erythrocyte sedimentation rates, digital ischaemia, and severity of pulmonary fibrosis. CONCLUSIONS: Up regulated expression of fractalkine and CX(3)CR1 cooperatively augments the recruitment of mononuclear cells expressing CX(3)CR1 into the affected tissue of SSc, leading to inflammation and vascular injury.     

Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease

Coronary atherosclerosis is a major cause of death in industrialized countries. Monocytes, which play a key role in atherosclerosis, migrate into the vessel wall, presumably guided by specific chemoattractant and adhesion molecules. A compelling candidate for this role is the chemokine receptor CX3CR1, which is expressed on monocytes and acts as either a chemotactic receptor or an adhesion molecule, depending on whether its ligand, fractalkine, is presented free or membrane bound. A common variant of CX3CR1 was recently identified, encoded by the alleles I249 and M280, which form a common I(249)M(280) haplotype. When CX3CR1 genotypes were analyzed in 151 patients with acute coronary syndromes and in 249 healthy controls, CX3CR1 I249 heterozygosity was associated with a markedly reduced risk of acute coronary events, independent of established acquired coronary risk factors (eg, smoking, diabetes). The adjusted odds ratio for this allele was 0.43 (95% confidence interval, 0.26-0.72; P =.001). Consistent with this, functional analysis of peripheral blood mononuclear cells showed that CX3CR1 I249 heterozygosity was associated with a significant decrease in the number of fractalkine binding sites per cell. The results show that CX3CR1 I249 is an independent genetic risk factor for coronary artery disease and that CX3CR1 may be involved in the pathogenesis of atherosclerotic disease. (Blood. 2001;97:1925-1928)     

Preliminary study correlating CX3CL1/CX3CR1 expression with gastric carcinoma and gastric carcinoma perineural invasion

AIM:To study the relationship between the CX3CL1chemokine,its receptor CX3CR1,and gastric carcinoma/gastric carcinoma perineural invasion(PNI).METHODS:Thirty cases of gastric carcinoma were surgically resected(radical resection or palliative resection)between February 2012 and July 2012.Tumour and tumour-adjacent tissues were evaluated for the presence of CX3CL1(ELISA)and CX3CR1(immunohistochemistry and Western blotting)in an effort to analyse the relationship between CX3CL1/CX3CR1 and gastric carcinoma/gastric carcinoma PNI.RESULTS:Of these 30 cases,14 were PNI-positive(46.7%).No significant differences in CX3CL and CX3CR1 expression in tumour-adjacent tissues were found between the PNI positive and negative groups.Expression levels of CX3CL and CX3CR1 in tumour tissues were significantly higher than those in adjacent tissues(P<0.01),and were significantly higher in tumour tissues from the PNI-positive group compared to the PNI-negative group(P<0.01).CONCLUSION:CX3CL1/CX3CR1 expression may be associated with the occurrence and development of gastric carcinoma as well as gastric carcinoma PNI.     

高血压伴冠心病患者冠状动脉狭窄与周围动脉功能关系的研究

目的分析冠状动脉的病变支数及狭窄程度与周围动脉弹性功能的关系。方法对88例高血压病患者与41例无高血压病临床怀疑冠心病的患者,在冠状动脉造影前后采用美国FDA批准的PULSEMETRIC动脉功能测定仪通过测定肱动脉脉搏图计算出反应血管弹性的参数,包括系统血管顺应性（SVC）、系统血管阻力（SVR）、肱动脉顺应性（BAC）及肱动脉阻力（BAR）,分析高血压伴及不伴冠状动脉病变者的动脉弹性的特点。结果（1）高血压组严重冠状动脉病变（冠状动脉病变〉12支以上）发生率[64．7％（57／88）]高于血压正常组[27．1％（11／41）,P〈0．05）;（2）高血压组的SVC[（0．85±0．10）ml／mmHg（1mmHg=0．133kPa）]、BAC[（0．047±0．011）ml／mmHg]明显低于非高血压组[SVC（1．17±0．11）ml／mmHg,BAC（0．063±0．010）ml／mmHg,均P〈0．05],高血压组的脉压则明显高于非高血压组[（78±20）mmHg比（47±19）ml／mmHg,P〈0．01];（3）高血压组内,动脉弹性有随冠状动脉病变加重而下降的趋势,而动脉弹性功能参数在不同的性别存在不同的变化;（4）当血压水平达到2～3级,SVC有随冠状动脉病变程度加重而降低的趋势。结论在高血压病患者中,无创方法测得的动脉功能参数在一定程度上可以反映其冠状动脉病变程度。     

Fractalkine-CX3CR1与肺疾病

Fractalkine(CX3CL1)是一种独特的趋化因子,是CX3C类惟一的代表,以膜结合型和可溶型两种类型存在,具有黏附和趋化双重作用,CX3CL1与其受体(CX3CR1)结合后可参与细胞的多种生理和病理过程,CX3CL1-CX3CR4表达与感染性肺疾病、肺动脉高压、慢性阻塞性肺疾病、哮喘及肺肿瘤等肺部疾病的发生、...     

冠状动脉钙化与冠状动脉狭窄的相关性研究

目的探究冠心病患者冠状动脉钙化积分与冠状动脉狭窄的相关性。方法入选54例冠心病住院患者,年龄52～84岁,（平均68.47±9.35）岁;其中男性36例,女性18例,行16层螺旋计算机断层扫描,计算冠状动脉钙化积分,并与冠状动脉造影进行比较,分析冠状动脉总钙化积分及各冠状动脉节段（共分16个节段）钙化积分与冠状动脉造影所示冠脉狭窄程度的相关性,同时分析冠状动脉总钙化积分与年龄的相关性。结果冠状动脉总钙化积分与年龄呈正相关（r=0.372,P=0.009）、冠状动脉总钙化积分仅与部分冠状动脉节段狭窄程度呈正相关：RA（1#）、LAD（7#）、D1（9#）、LCX（11#）,（相关系数、P值分别为：r=0.499,P〈0.01;r=0.431,P〈0.01;r=0.440,P〈0.01;r=0.469,P〈0.01）。冠状动脉各节段钙化积分与对应血管节段狭窄程度相关分析结果提示：RA（1#）、LM（5#）、LCX（11#）节段钙化积分与对应节段狭窄程度呈正相关。结论总冠状动脉钙化积分与年龄呈正相关,提示随年龄增长冠状动脉钙化发生率增加,但冠状动脉钙化积分仅在部分冠状动脉节段与狭窄程度呈正相关,且限于三支冠状动脉近段。     

老年患者血清25羟维生素D3与冠状动脉狭窄程度的相关性研究

目的探讨血清25羟维生素D3与老年患者冠状动脉狭窄程度相关性。方法对269例老年患者行冠状动脉造影术,分为狭窄组114例和正常组155例,应用Gensini积分判断冠状动脉狭窄程度。测定血清25羟维生素D3水平,按照25羟维生素D3四分位数分为:Q1组(<15.0nmol/L)60例,Q2组(15.0~22.1nmol/L)74例,Q3组(22.2~35.6nmol/L)68例,Q4组(>35.6nmol/L)67例。结果狭窄组与正常组25羟维生素D3比较,差异有统计学意义[(25.05±16.08)nmol/L vs(31.83±22.36)nmol/L,P=0.004];Q1组、Q2组、Q3组与Q4组Gensini积分比较,差异有统计学意义(P<0.05,P<0.01)。血清25羟维生素D3与C反应蛋白呈负相关(r=-0.548,P=0.000),与Gensini评分呈负相关(r=-0.183,P=0.003)。多元logistic回归分析显示,血清25羟维生素D3是老年患者冠状动脉狭窄独立保护因素(P<0.01)。结论低水平25羟维生素D3与老年患者冠状动脉狭窄程度相关,需进一步研究证实补充25羟维生素D3是否会减少老年冠心病的发病。