血清MMP-8、IL-6表达与缺血性脑血管病患者颈动脉粥样硬化斑块的关系研究

目的：研究血清基质金属蛋白酶-8(MMP-8)、白细胞介素-6(IL-6)表达与缺血性脑血管病患者颈动脉粥样硬化斑块的关系。 方法：选取2012 年9 月至2013 年11 月就诊60 例缺血性脑血管病患者为研究组和健康体检者60 例为对照组。按照超声影像学 资料并参考患者颈动脉斑块类型把研究组分为不稳定斑块类型(18 例),稳定斑块类型(22 例)以及斑块性质介于两组之间为中间 类型(20 例)。采用双抗体夹心酶联免疫吸附试验(ELISA)对血清MMP-8、IL-6 水平进行测定,探讨血清MMP-8、IL-6 表达与不同 程度缺血性脑血管病患者颈动脉粥样硬化斑块的关系。结果：研究组血清MMP-8、IL-6 水平显著高于对照组,差异均有统计学意 义(P<0.01);三种不同类型斑块血清中MMP-8、IL-6 水平差异均有统计学意义(P<0.01);Spearman 等级相关性分析发现,研究组患 者颈动脉斑块稳定程度与血清MMP-8、IL-6 浓度水平存在显著正相关关系(P<0.01);线性相关分析发现,研究组血清MMP-8 水 平与IL-6 水平呈正相关关系(P<0.01)。结论：缺血性脑血管病患者血清MMP-8、IL-6 水平明显升高,其与颈动脉斑块不稳定程度 相关,同样与缺血性脑血管病发病机制方面存在相关协同作用。     

急性脑梗死患者颈动脉斑块与基质金属蛋白酶、血清白介素及多肽生长因子的关系研究

目的:探讨基质金属蛋白酶、血清白介素及多肽生长因子与急性脑梗死患者颈动脉斑块的关系。方法:选取于2017年1月至2017年12月期间北京中医药大学第三附属医院老年病科收治的60例急性脑梗死患者作为观察组,根据彩色多普勒超声检测仪进行颈动脉超声检查,将结果分为无斑块组(20例),稳定斑块组(20例)和不稳定斑块组(20例),选取同期的60例门诊体检健康者作为对照组。采用双抗体夹心酶标免疫吸附法(ELISA)测定血清基质金属蛋白酶MMP-7、MMP-9、MMP-12水平,血清白介素IL-6、IL-8、IL-18以及血清多肽生长因子VEGF和TGF-β1水平,对观察组及对照组的检测结果以及无斑块组、稳定斑块组、不稳定斑块组及对照组的检测结果进行分析研究。结果:观察组的血清基质金属蛋白酶MMP-7、MMP-9、MMP-12水平,血清白介素IL-6、IL-8、IL-18水平以及血清多肽生长因子VEGF水平显著高于对照组,差异有统计学意义(P0.05),观察组的血清多肽生长因子TGF-β1水平则显著低于对照组,差异有统计学意义(P0.05)。稳定性斑块组体质指数显著高于对照组(P0.05);不稳定性斑块组与对照组相比,BMI、TC及TG水平均显著升高(P0.05),且与无斑块组相比,甘油三酯水平也偏高(P0.05)。无斑块组,稳定斑块组及不稳定斑块组的血清基质金属蛋白酶MMP-7、MMP-9、MMP-12水平,血清白介素IL-6、IL-8、IL-18水平以及血清多肽生长因子VEGF和TGF-β1水平比较,差异有统计学意义(P0.05),其中除血清多肽生长因子TGF-β1水平显著低于其它2组外,不稳定斑块组的血清基质金属蛋白酶MMP-7、MMP-9、MMP-12水平,血清白介素IL-6、IL-8、IL-18水平以及血清VEGF水平显著高于其它2组,差异有统计学意义(均P0.05)。结论:急性脑梗死患者的血清基质金属蛋白酶、血清白介素以及血清多肽生长因水平与颈动脉斑块密切相关。     

HGF及血清炎症因子的变化与CAS严重程度的相关性分析

为了探讨血清肝细胞生长因子(HGF)、基质金属蛋白酶9 (MMP-9)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、乳脂球表皮生长因子-8 (MFG-G8)、细胞间黏附分子-1 (ICAM-1)与颈动脉粥样硬化(CAS)严重程度的相关性,本研究选取颈动脉彩超诊断的CAS的患者120例(CAS组)、60例颈动脉无病变的研究对象(对照组),对比两组血清HGF及炎症因子水平,并根据颈动脉内中膜厚度(IMT)进行亚组分析。研究显示,CAS组血清HGF、MMP-9、TNF-α、IL-1β、MFG-G8、ICAM-1水平显著高于对照组,差异具有统计学意义(p0.05);CAS组120例患者中IMT增厚患者有70例、颈动脉粥样斑块形成患者有50例,IMT增厚患者血清HGF、MMP-9、TNF-α、IL-1β、MFG-G8、ICAM-1水平显著低于颈动脉粥样斑块形成,差异具有统计学意义(p0.05);CAS组120例患者平均IMT厚度为(1.29±20) mm,CAS患者的血清HGF、MMP-9、TNF-α、IL-1β、MFG-G8、ICAM-1水平与IMT均呈显著正相关(p0.05),且CAS患者的血清HGF、MMP-9、TNF-α、IL-1β、MFG-G8、ICAM-1水平显著升高。说明HGF及各炎症因子与颈动脉粥样硬化关系密切。     

脑梗死患者内脂素和基质金属蛋白酶-9 与颈动脉粥样硬化 斑块易损性的关系

目的：探讨血清内脂素（Visfatin）及基质金属蛋白酶-9（MMP-9）水平与脑梗死患者颈动脉粥样硬化斑块稳定性的关系和血 清visfatin 和MMP-9 的相关性。方法：选择脑梗死患者70 例,根据颈动脉粥样硬化斑块性质分为易损性斑块组(n=43)和非易损 性斑块组(n=27),选取健康体检者30 例作为对照组。测定血清Visfatin 和MMP-9 水平,并对二者间关系进行相关分析。结果：脑 梗死伴颈动脉硬化组血清Visfatin、MMP-9 水平高于正常对照组(P＜0.01);易损性斑块组血清Visfatin 和MMP-9 水平高于非易 损性斑块组,差异有统计学意义（P＜0.017）。外周血中的Visfatin水平与MMP-9 呈正相关关系（r=0.643,P=0.000）。结论：在脑梗 死患者中,血清Visfatin和MMP-9 参与了颈动脉粥样硬化的病理生理过程,Visfatin 和MMP-9升高可能与颈动脉粥样硬化斑块 不稳定性的形成相关,Visfatin 可通过调控MMP-9 的分泌和活性从而改变斑块的易损性。     

急性缺血性脑卒中患者血浆Lp-PLA2 的表达及与斑块稳定性及神经功 能缺损的关系

目的：探讨急性缺血性脑卒中患者血浆脂蛋白相关磷脂酶（Lp-PLA2）的表达及与斑块稳定性及神经功能缺损的关系。方法： 按照颈动脉彩超结果将2014 年5 月-2015 年1 月我院收治的80 例急性缺血性脑卒中患者分为斑块稳定组（25 例）、斑块不稳定 组（39 例）和无斑块组（16 例）,并于同期随机抽取120 例健康体检者为对照组。采用散射比浊法测定各组血浆Lp-PLA2,同时采 用美国国立卫生研究所中风量表（NIHSS 评分）对三组的神经功能缺损情况进行评估。结果：斑块稳定组、斑块不稳定组以及无斑 块组血浆Lp-PLA2 高于对照组,斑块稳定组、斑块不稳定组高于无斑块组,斑块不稳定组高于斑块稳定组,差异均有统计学意义 （P<0.05）,患者血浆Lp-PLA2水平与动脉粥样硬化斑块的稳定性呈正相关性（rs=0.638,P<0.05）。神经功能缺损中型组、重型组血 浆Lp-PLA2 高于轻型组,重型组高于中型组,差异有统计学意义（P<0.05）,患者血浆Lp-PLA2 水平与神经功能缺损程度呈正相关 性（rs=0.715,P<0.05）。结论：血浆Lp-PLA2 可作为预测急性缺血性脑卒中患者颈动脉硬化斑块稳定性以及评估患者神经功能缺 损程度的重要指标。     

脑梗死患者内脂素和基质金属蛋白酶-9与颈动脉粥样硬化斑块易损性的关系

目的：探讨血清内脂素（Visfatin）72．基质金属蛋白酶-9（MMP-9）水平与脑梗死患者颈动脉粥样硬化王囊￡块稳定性的关系和血清visfatin和MMP-9的相关性。方法：选择脑梗死患者70例,根据颈动脉粥样硬化斑块性质分为易损性斑块组（n=43）和非易损性斑块组（n=27）,选取健康体检者30例作为对照组。测定血清Visfatin和MMP-9水平,并对二者间关系进行相关分析。结果：脑梗死伴颈动脉硬化组血清Visfatin、MMP-9水平高于正常对照组（P〈0．01）;易损性斑块组血清Visfatin和MMP．9水平高于非易损性斑块组,差异有统计学意义（P〈0．017）。外周血中的Visfatin水平与MMP-9呈正相关关系（r=0．643,P=0．000）。结论：在脑梗死患者中,血清Visfatin和MMP-9参与了颈动脉粥样硬化的病理生理过程,Visfatin和MMP-9升高可能与颈动脉粥样硬化斑块不稳定性的形成相关,Visfatin可通过调控MMP一9的分泌和活性从而改变斑块的易损性。     

血清尿酸水平对急性脑梗死患者颈动脉粥样硬化斑块的影响

目的:探讨血清尿酸(UA)水平对急性脑梗死患者颈动脉粥样硬化斑块的影响。方法:回顾性分析2011年6月至2016年1月我院收治的251例急性脑梗死患者的临床资料,根据有无颈动脉粥样硬化斑块分为伴颈动脉粥样硬化斑块组(观察组)176例和无颈动脉粥样硬化斑块组(对照组)75例,观察组根据颈动脉粥样硬化程度分为斑块形成组(113例)、内中膜增厚组(63例),根据颈动脉斑块稳定程度分为不稳定组(106例)、稳定组(70例),比较各组血清UA水平,根据UA水平不同分为高UA组(134例)和正常UA组(117例),进行颈动脉斑块发生情况比较。结果:观察组的血清UA水平显著高于对照组,差异有统计学意义(P0.05)。(1)斑块形成组和内中膜增厚组血清UA水平显著高于对照组(P0.05),而斑块形成组和内中膜增厚组血清UA水平比较,差异无统计学意义(P0.05);(2)不稳定组血清UA水平显著高于对照组和稳定组(P0.05),而稳定组和对照组血清UA水平比较,差异无统计学意义(P0.05);(3)正常UA组和高UA组颈动脉斑块的发生情况比较,差异无统计学意义(P0.05)。结论:血清UA水平可以作为表征急性脑梗死患者伴随出现颈动脉粥样硬化斑块的生物学指标之一,此外,血清UA的水平在颈动脉粥样硬化斑块形成者和不稳定者表达更高,但血清UA水平与颈动脉斑块形成无明显联系。     

TNF-alpha、IL-6及IL-8在不同程度溃疡性结肠炎患者血清中的表达及意义

目的：探讨不同严重程度溃疡性结肠炎患者血清TNF-alpha、IL-6 及IL-8 的表达及意义。方法：选择2011 年1 月~2014 年7 月 我院收治的溃疡性结肠炎患者47 例,根据严重程度将患者分为轻度组、中度组和重度组。另选取同期在我院接受健康体检的志 愿者80 例作为对照组。采用酶联免疫吸附试验（ELISA）检测各组患者血清TNF-alpha、IL-6 及IL-8 的水平。结果：溃疡性结肠炎患者 血清TNF-琢、IL-6 及IL-8 水平高于对照组,差异有统计学意义（P<0.05）;不同严重程度溃疡性结肠炎患者的TNF-alpha、IL-6 及IL-8 水平呈显著差异（P<0.05）。结论：检测溃疡性结肠炎患者血清TNF-alpha、IL-6 及IL-8的水平变化有利于预测病情进展。     

老年急性脑梗死患者外周血EMMPRIN表达与颈动脉易损斑块的相关性

目的:分析老年急性脑梗死(acute cerebral infarction,ACI)患者外周血血小板表面细胞外基质金属蛋白酶诱导因子(EMMPRIN)表达与颈动脉易损斑块的相关性。方法:收集2017年3月至2019年3月于我院收治的老年ACI患者作为研究对象,按照超声下颈动脉斑块的分类标准,将颈动脉斑块呈高回声受检者纳入稳定斑块组(n=41),斑块呈低回声或等回声的受检者则纳入易损斑块组(n=52)。应用logisitc回归模型,分析ACI患者颈动脉易损斑块的影响因素;采用Pearson相关分析,研究外周血单个核细胞EMMPRIN与各临床指标的相关性;采用受试者工作特征(ROC)曲线评价EMMPRIN诊断颈动脉易损斑块的准确性。结果:易损斑块组高脂血症、高血压病、2型糖尿病比例以及FPG、IL-6、IL-1β、MMP-9、MCP-1、TNF-α、LDL、EMMPRIN水平均高于稳定斑块组,组间差异显著(P0.05);易损斑块组HDL水平均低于稳定斑块组,组间差异显著(P0.05)。person相关分析结果显示,EMMPRIN与IL-6、IL-1β、MMP-9、TNF-α均呈正相关(r=0.348,0.374,0.418,0.427,P0.05)。logistic多因素回归分析显示,结果显示,高血压病、2型糖尿病、IL-1β、MMP-9、EMMPRIN均为颈动脉易损斑块的危险因素。EMMPRIN的AUC优于MMP-9、IL-1β(P=0.016,0.039,均P0.05)。结论:外周血血小板表面EMMPRIN水平可能与老年ACI患者颈动脉斑块稳定性有关,可作为辅助临床诊断颈动脉易损斑块的预警指标,对于ACI的发生、发展均具有重要的临床意义。     

脂蛋白相关磷脂酶A2对急性前循环脑梗死患者颈动脉斑块易损性的预测价值

目的:探讨脂蛋白相关磷脂酶A2(Lp-PLA2)对急性前循环脑梗死患者颈动脉斑块易损性的预测价值。方法:选取2015年9月至2017年3月我院收治的急性前循环脑梗死患者150例作为研究组,另选同期我院体检健康者100例作为对照组,检测两组血清Lp-PLA2、超敏C反应蛋白(hs-CRP)水平,并应用彩色多普勒超声检查研究组患者颈动脉粥样硬化情况,分析不同颈动脉粥样硬化情况以及不同病情患者血清Lp-PLA2、hs-CRP、颈动脉内膜-中层厚度(IMT),并分析血清Lp-PLA2对颈动脉斑块易损性的预测价值。结果:研究组血清Lp-PLA2、hs-CRP和IMT均显著高于对照组(P0.05)。易损斑块组、稳定斑块组、内膜增厚组血清Lp-PLA2、hs-CRP和IMT均显著高于内膜正常组,易损斑块组、稳定斑块组血清Lp-PLA2、hs-CRP和IMT均显著高于内膜增厚组(P0.05),易损斑块组血清Lp-PLA2、hs-CRP显著高于稳定斑块组(P0.05),而IMT比较无统计学差异(P0.05)。重度组、中度组脑梗死患者血清Lp-PLA2、hs-CRP和IMT均显著高于轻度组,重度组脑梗死患者血清Lp-PLA2、hs-CRP和IMT显著高于中度组(P0.05)。ROC曲线显示血清Lp-PLA2、hs-CRP对脑梗死患者颈动脉斑块易损性预测的曲线下面积(AUC)分别为0.809(95%CI:0.739-0.883)、0.598(95%CI:0.495-0.694),血清Lp-PLA2对脑梗死患者颈动脉斑块易损性的预测价值显著高于hs-CRP(P0.05)。结论:急性前循环脑梗死患者血清Lp-PLA2出现异常升高,其水平可以反映颈动脉斑块易损性,可为脑梗死诊断提供依据。     

Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques

The association between iron, an oxidant catalyst, and atherosclerosis is controversial. In particular, it is unknown whether: (1) stored iron, namely serum ferritin, is correlated with catalytic iron and oxidant damage of human atherosclerotic plaques; (2) catalytic iron is related to oxidative injury within such plaques; (3) plaque oxidant burden is associated with the severity of atherosclerosis. Thus, we assessed low molecular weight iron (LMWI), which represents the metal catalytically active form, together with fluorescent damage products of lipid peroxidation (FDPL) and lipid hydroperoxides (LOOH), in 38 atherosclerotic plaques surgically removed from 38 patients who had undergone selective carotid endarterectomy. In each patient, the levels of serum ferritin were measured and correlated with those of plaque LMWI and lipoperoxides by the Spearman rank correlation test with Spearman rank correlation coefficient (r(S)) calculation. Moreover, in patients selected from the same study population, we compared plaque analyte levels between two groups with different severity of atherosclerotic carotid stenosis, i.e., <90% (group A, n = 25) or > or =90% (group B, n = 13), and between another two groups without (group C, n = 27) and with (group D, n = 11) associated contralateral carotid stenosis > or =50%, indicative of "extensive" and more severe atherosclerotic disease. In group A patients, serum ferritin was directly and significantly correlated with plaque LMWI (r(S) = 0.46, P < 0.025) and FDPL (r(S) = 0.58, P < 0.005), while its correlation with plaque LOOH, albeit direct, did not attain statistical significance. Moreover, a direct and significant relationship was evident between the plaque content of LMWI and that of both FDPL (r(S) = 0.61, P < 0.0025) and LOOH (r(S) = 0.51, P < 0.025), suggesting a prooxidant role of catalytic iron within human atherosclerotic plaques. Considering the 13 patients of group B, a positive and significant correlation was observed between the levels of serum ferritin and those of plaque LMWI (r(S) = 0.83, P < 0.0001); on the other hand, serum ferritin, as well as plaque LMWI, showed no significant correlation with either plaque FDPL or LOOH, conceivably reflecting the small number of patients belonging to group B. Finally, plaque LMWI, FDPL, and LOOH content was significantly higher in group B than in group A, and in group D than in group C. These data suggest a role for catalytic iron in atherosclerotic plaque oxidation and in the severity of atherosclerosis, which appears indeed associated with plaque oxidant burden.     

不同类型缺血性脑血管病血清VCAM-1、MMP-2、TIMP-1的表达及与神经功能缺损的关系分析

摘要 目的：探讨不同类型缺血性脑血管病血清血管细胞粘附分子-1（VCAM-1）、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶抑制剂1（TIMP-1）的表达及与神经功能缺损的关系。方法：选择2016年1月至2020年1月我院接诊的98例缺血性脑血管病患者为本研究对象,其中脑梗死55例设为脑梗死组,短暂性脑缺血发作组43例,并选择我院同期体检中心健康者50作为对照组,分析三组血清VCAM-1、MMP-2、TIMP-1水平之间的差异及不同神经缺损程度血清VCAM-1、MMP-2、TIMP-1水平、美国国立卫生研究院卒中量表（NIHSS）评分变化情况,及其之间的相关性。结果：脑梗死组血清VCAM-1、MMP-2、TIMP-1水平及NIHSS评分显著高于短暂性脑缺血发作组和对照组,差异显著（P＜0.05）;短暂性脑缺血发作组血清VCAM-1、MMP-2、TIMP-1水平及NIHSS评分显著高于对照组,差异显著（P＜0.05）;重度神经缺损组血清VCAM-1、MMP-2、TIMP-1水平及NIHSS评分显著高于中度神经缺损组和轻度神经缺损组,差异显著（P＜0.05）;中度神经缺损组血清VCAM-1、MMP-2、TIMP-1水平及NIHSS评分显著高于轻度神经缺损组,差异显著（P＜0.05）;相关性分析结果中显示,血清VCAM-1、MMP-2、TIMP-1均和NIHSS评分呈正相关（r=0.603, 0.915, 0.778,P＜0.05）。结论：血清VCAM-1、MMP-2、TIMP-1在缺血性脑血管病患者中表达异常,神经缺损越严重血清VCAM-1、MMP-2、TIMP-1表达越高。     

急性脑梗死患者颈动脉斑块内新生血管超声造影评价及其与血清YKL-40蛋白及Lp-PLA2水平的相关性分析

目的:探讨急性脑梗死(ACI)患者颈动脉斑块内新生血管超声造影的评估价值,分析其分级与患者病情严重程度、预后以及血清甲壳质酶蛋白(YKL-40)和脂蛋白相关磷脂酶A2(Lp-PLA2)水平的相关性。方法:选择2016年2月至2019年6月我院收治的102例ACI患者,进行颈动脉彩超、超声造影和血清YKL-40、Lp-PLA2检测,采用美国国立卫生院神经功能缺损评分(NIHSS)评价ACI患者病情严重程度,所有患者随访至发病后4周统计预后。结果:易损斑块组颈动脉斑块造影分级、血清YKL-40、Lp-PLA2水平高于稳定斑块组和无斑块组(P0.05)。不同病情程度组、不同预后组颈动脉斑块内新生血管造影分级均具有统计学差异(P0.05)。血清YKL-40、Lp-PLA2水平随着ACI病情程度的加重而升高(P0.05),预后不良组血清YKL-40、Lp-PLA2水平高于预后良好组(P0.05)。Spearman秩相关结果显示,颈动脉斑块内新生血管造影分级与血清YKL-40、Lp-PLA2水平均呈正相关(rs=0.751、0.694,P0.05)。结论:ACI患者的颈动脉易损斑块内新生血管超声造影分级高,其分级与病情严重程度、预后以及血清YKL-40、Lp-PLA2水平均存在密切关系,颈动脉超声造影可为ACI病情危险分层、预后判断提供有效依据。     

Simultaneous measurement of multiple Th1 and Th2 serum cytokines in psoriasis and correlation with disease severity

BACKGROUND: Psoriatic plaques have been shown to contain increased levels of proinflammatory cytokines. Serum levels of interleukin (IL)-6, IL-7, IL-8, and interferon (IFN)-gamma have been reported elevated in psoriatic patients. AIM: To evaluate serum cytokine profiles in psoriasis patients by improved enzyme-linked immunosorbent assay (ELISA) technique and to correlate these levels with disease severity. METHODS: We analyzed single serum samples from 10 patients with active untreated psoriasis, two patients with active treated psoriasis, and five healthy volunteers for major T helper type 1 and T helper type 2 cytokines using the LINCOplex ELISA multi-analyte detection system that permits simultaneous detection of multiple cytokines from a single sample. The disease severity, including erythema, induration, scale, and surface area, was assessed. RESULTS: IFN-gamma was markedly elevated in all sera from psoriasis patients, 33.8 +/- 1.3 pg/ml (mean +/- standard error) versus 8 +/- 1.5 pg/ml for normal controls (p < 0.01), and positively correlated with all indices of disease severity (Spearman r > 0.6). IL-8 was also increased in psoriasis patients (24.4 +/- 1.8 pg/ml) versus normal controls (3.6 +/- 1.2 pg/ml) (p < 0.05) and positively correlated with the degree of erythema (Spearman r > 0.6). Mean IL-12 levels were decreased in sera from psoriasis patients (8.5 +/- 1.2 pg/ml) compared with normal controls (42.2 +/- 5.3 pg/ml) (p < 0.01). Also, serum IL-10 levels were below detection levels in psoriatics compared with controls (6.4 +/- 1.3 pg/ml). CONCLUSIONS: This new ELISA system allowed rapid and reliable detection of numerous cytokines in single serum samples from patients with psoriasis. We observed that IFN-gamma and IL-8 cytokines were elevated in psoriatics and correlated with parameters of disease severity while IL-10 and IL-12 were decreased.     

Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease

Caveolin-1 (Cav-1) is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin) reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice. This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target in the prevention of human atherosclerotic disease and the loss of Cav-1 may be a novel biomarker of vulnerable plaque with prognostic value.     

Matrix Metalloproteinase 7 Is Associated with Symptomatic Lesions and Adverse Events in Patients with Carotid Atherosclerosis

Background

Atherosclerosis is a major cause of cerebrovascular disease. Matrix metalloproteinases (MMPs) play an important role in matrix degradation within the atherosclerotic lesion leading to plaque destabilization and ischemic stroke. We hypothesized that MMP-7 could be involved in this process.

Methods

Plasma levels of MMP-7 were measured in 182 consecutive patients with moderate (50–69%) or severe (≥70%) internal carotid artery stenosis, and in 23 healthy controls. The mRNA levels of MMP-7 were measured in atherosclerotic carotid plaques with different symptomatology, and based on its localization to macrophages, the in vitro regulation of MMP-7 in primary monocytes was examined.

Results

Our major findings were (i) Patients with carotid atherosclerosis had markedly increased plasma levels of MMP-7 compared to healthy controls, with particularly high levels in patients with recent symptoms (i.e., within the last 2 months). (ii) A similar pattern was found within carotid plaques with markedly higher mRNA levels of MMP-7 than in non-atherosclerotic vessels. Particularly high protein levels of MMP-7 levels were found in those with the most recent symptoms. (iii) Immunhistochemistry showed that MMP-7 was localized to macrophages, and in vitro studies in primary monocytes showed that the inflammatory cytokine tumor necrosis factor-α in combination with hypoxia and oxidized LDL markedly increased MMP-7 expression. (iv) During the follow-up of patients with carotid atherosclerosis, high plasma levels of MMP-7 were independently associated with total mortality.

Conclusion

Our findings suggest that MMP-7 could contribute to plaque instability in carotid atherosclerosis, potentially involving macrophage-related mechanisms.     

Measurement of gp130 cytokines oncostatin M and IL-6 in gingival crevicular fluid of patients with chronic periodontitis

Several proinflammatory cytokines can induce periodontal tissue destruction and are thought to be useful indicators or diagnostic markers for periodontitis. Here, we aimed to investigate whether oncostatin M (OSM) was present in gingival crevicular fluid (GCF) and to clarify the correlation of GCF OSM and interleukin-6 (IL-6) levels with the severity of periodontitis. Sixty-two sites in 14 patients were divided into 4 groups based on probing depth (PD) and bleeding on probing (BOP). GCF was collected using paper strips from clinically health sites (PD < or = 3 mm, CAL: 1-3 mm, without BOP, n = 31), mildly diseased sites (PD < or = 3 mm, CAL: 3-5 mm, with BOP, n = 11), moderately diseased sites (PD = 4-6 mm, CAL: 5-8 mm, with BOP, n = 11), and severely diseased sites (PD > 6 mm, CAL: 8-12 mm, with BOP, n = 9). IL-6 and OSM in GCF were quantified by enzyme-linked immunosorbent assay and are expressed as concentrations (pg/ml) and total amounts (pg/site). Correlations of OSM and IL-6 levels with the severity of periodontitis in all groups were determined using Spearman rank correlation (r(s)). Our results showed that OSM and IL-6 were detected in most GCF samples. The total amounts of OSM and IL-6 were significantly positive correlated with severity of diseased sites (OSM: r(s) = 0.526, p < 0.01; IL-6: r(s) = 0.729, p < 0.01). No correlations of OSM or IL-6 concentration in GCF were found with disease severity. OSM and IL-6 levels in GCF were positively correlated to each other when expressed as either concentrations or total amounts (concentrations: r = 0.485, p < 0.01; total amounts r = 0.490, p < 0.01). In conclusion, our findings suggest that IL-6 and OSM may play a role in modulating the inflammatory cascade of chronic periodontitis.     

颈动脉斑块易损性与血脂指标、炎症因子和冠心病的关系

目的:探讨颈动脉斑块易损性与血脂指标、炎症因子和冠心病的关系。方法:选择2016年1月-2018年1月在我院进行治疗的颈动脉斑块患者95例为研究对象,所有患者均进行颈动脉超声检查,根据超声检查结果的斑块性质将患者分为稳定组(n=43)和易损组(n=52)。检测两组患者的总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)等血脂指标,对比两组患者的血清白介素-8(IL-8)、超敏C反应蛋白(hs-CRP)、细胞黏附因子-1(ICAM-1)、趋化因子(RANTES)水平,统计两组患者的冠心病发生率。结果:易损组患者的TC、TG、LDL-C均高于稳定组,HDL-C低于稳定组,组间比较差异有统计学意义(P0.05)。易损组患者的IL-8、hs-CRP、ICAM-1、RANTES水平均高于稳定组,组间比较差异有统计学意义(P0.05)。稳定组冠心病发生率为53.49%(23/43),易损组冠心病发生率为78.85%(41/52),两组冠心病发生率比较差异有统计学意义(P0.05)。结论:颈动脉斑块易损性可导致患者的血脂指标、血清炎症因子指标进一步恶化,也会增加患者出现冠心病的发生机率。