NLRP3 and downstream cytokine expression elevated in the monocytes of patients with coronary artery disease

Introduction

Pattern recognition receptor (PRR)-mediated signaling pathways have recently been elucidated to bridge the innate immune system and atherosclerosis. NLRP3 is among the family members of NOD-like receptors (NLRs), a type of PRRs. At present, most studies about the NLRP3 inflammasome focus on animal models and immune cells. Limited information is available regarding the role of NLRP3 in patients with coronary artery disease (CAD).

Material and methods

In this study, we observed the expression of NLRP3 and downstream cytokines in patients with CAD by ELISA, real-time qPCR and Western blot.

Results

We found that NLRP3 and downstream cytokines were coupled with increasing severity of CAD and a dynamic variation exists in patients with acute myocardial infarction. We also found that NLRP3 was correlated with Gensini score, indicating that NLRP3 might be relevant not only for the severity of CAD but also for the severity of coronary atherosclerosis.

Conclusions

This study provides a new theoretical basis for innate immune participation in atherosclerosis development and highlights the potential of the NLRP3 inflammasome as a target for prevention and treatment of CAD.     

Analysis of CD154 and CD40 expression in native coronary atherosclerosis and transplant associated coronary artery disease

T cells have roles in the pathogenesis of native coronary atherosclerosis (CA) and transplant-associated coronary artery disease (TCAD). The mechanisms by which T cells interact with other cells in these lesions are not fully known. CD154 is an activation-induced CD4⁺ T cell surface molecule that interacts with CD40⁺ target cells, including macrophages and endothelial cells, and induces the production of pro-inflammatory molecules, including CD54 (ICAM-1) and CD106 (VCAM-1). To investigate whether CD154-CD40 interactions might be involved in the pathogenesis of CA or TCAD we performed immunohistochemical studies of CD154 and CD40 expression on frozen sections of coronary arteries obtained from cardiac allograft recipients with CA (n=10) or TCAD (n=9). Utilizing four different anti-CD154 mAb we found that CD154 expression was restricted to infiltrating lymphocytes in CA and TCAD. CD40 expression was markedly up-regulated on intimal endothelial cells, foam cells, macrophages and smooth muscle cells in both diseases. Dual immunolabeling demonstrated many CD40⁺ cells co-expressed CD54 and CD106. The extent of CD40, CD54 and CD106 expression showed statistical significant correlation with the severity of disease and the amount of intimal lymphocytes. Together these studies demonstrate the presence of activated CD154⁺ and CD40⁺ cells in both CA and TCAD lesions and suggest that CD154-mediated interactions with CD40⁺ macrophages, foam cells, smooth muscle cells and/or endothelial cells may contribute to the pathogenesis of these diseases. Received: 17 December 1999 / Accepted: 20 January 2000     

冠心病冠状动脉搭桥术前后心电图变化的研究

目的探讨冠心病人冠状动脉搭桥术(CABG)前后心电图的变化。方法通过25例冠心病CAGB患者术前与术后7天、14天、21天及30天阶段比较心电图的动态变化。结果与术前(4.5±2.3天)比较,ST段压低>1.0mm。T波低平、双向和倒置第一周显著增多,此后ST段压低者减少到术前水平,T波低平、双向和倒置非常显著地减少。结论冠心病患者CABG后出现一过性ST段压低变化,T波低平、双向和倒置,此后上述改变逐渐减少至恢复到术前水平。     

Inflammatory cytokine levels in patients with periodontitis and/or coronary heart disease

The purpose of this study was to investigate systemic and local levels of four classic inflammatory cytokines (IL-1β, MCP-1, VEGF, PDGF) in patients with periodontitis and coronary heart disease (CHD). 109 volunteers were enrolled and the condition of their periodontal tissue and coronary artery were assessed. The patients were then divided into four distinct groups: periodontitis only, CHD only, periodontitis with CHD, and healthy controls. Gingival crevicular fluid (GCF) and venous blood were collected. The concentrations of cytokines were detected meanwhile by specific ELISA. The IL-1β and MCP-1 concentrations in the serum and GCF of the three disease groups were significantly higher than those in the control group (P ≤ 0.05). Serum VEGF concentrations of the patients with existing disease was lower than that of the controls. VEGF levels in the GCF of all disease groups were significantly higher than that of the control group (P ≤ 0.05).     

冠心病患者心率变异性指标与冠状动脉病变程度的关系

目的:探讨心率变异性指标与冠心病患者冠脉病变程度的关系。方法:选取冠心病患者84例（观察组）,同时选取健康志愿者90例作为对照组,均给予24 h动态心电图监测。结果:观察组NN间期的标准差（SDNN）、RR间期的均值标准差（SDANN）、相邻RR间期差值的均方根（RMSSD）、相邻RR间期差值>50 ms的心搏数所占百分比（PMN50）和高频功率（HF）分别为（95.54±20.12） ms、（94.48±21.15） ms、（29.84±10.06） ms、（7.46±2.31）%和（0.85±0.20） Hz,明显低于对照组（P<0.05）,而低频功率（LF）为（137.74±21.16） Hz,明显高于对照组（P<0.05）;冠状动脉病变≥3支患者SDNN、SDANN、RMSSD、PMN50和HF分别为（84.31±19.64） ms、（89.42±18.82） ms、（23.38±7.15） ms、（5.40±1.90）%和（0.70±0.21） Hz,明显低于冠状动脉病变数为1支和2支患者（P<0.05）,而LF为（150.54±21.15） Hz,明显高于冠状动脉病变数为1支和2支患者（P<0.05）;观察组男女患者SDNN、SDANN、RMSSD、PMN50、HF和LF比较差异无统计学意义（P>0.05）;Gensini评分与SDNN、SDANN、RMSSD、PMN50、HF呈负相关（r=-0.511、-0.487、-0.543、-0.512和-0.507, P<0.05）,与LF呈正相关（r=0.577, P<0.05）。结论:动态心电图在冠心病患者冠脉病变程度评价中有一定应用价值,其心率变异性指标与冠状动脉病变程度有一定关系。     

Study on the Anti-Cerebral Ischemia Effect of Borneol and Its Mechanism

Background

Borneol is the processed item from resin of Dryobalanops aromatica Gaertn. f. It can enhance the activity of antioxidant enzymes in brain tissue and reduce inflammatory response by improving the energy metabolism of ischemic brain regions, and thereby reduces brain tissue damage. The objective of this paper was to study the anti-cerebral ischemia effect of borneol and its mechanism.

Materials and Methods

The anti-cerebral ischemia effect of borneol was studied by ligation of bilateral common carotid arteries (CCA), and vagus nerves in mice and the acute cerebral ischemia-reperfusion experiment in rats.

Results

Compared with the blank and solvent control groups, the borneol low-; medium-; and high-dose groups can significantly prolong the gasping time of mice after decapitation, and extend the survival time of mice after ligation of bilateral CCA, and vagus nerves.

Conclusion

Compared with the Xueshuantong injection group, the prolongation of survival time of mice after ligation of bilateral CCA, and vagus nerves was more apparent in the high-dose borneol experimental group; each experimental group can significantly reduce the number of leukocyte infiltration, the number of ICAM-1-positive vessels, as well as the number of TNF-α-positive cells.

Conclusion

Borneol has an anti-cerebral ischemia effect.     

姜黄素对阿尔茨海默病大鼠学习记忆及HMGB1和JNK表达的影响

 目的：探讨姜黄素对阿尔茨海默病（AD）大鼠学习记忆能力、海马高迁移率族框蛋白1 （HMGB1）及c-Jun氨基末端激酶（JNK）表达的影响。方法: 36只雄性SD大鼠随机分为4组：空白对照组（A组）、AD模型组（B组, 鹅膏覃氨酸Meynert基底核注射）、AD模型+姜黄素治疗组（C组,腹腔注射100 mg·kg-1·d-1持续6 d）和AD模型+溶剂对照组（D组, 腹腔注射4 mL/kg玉米油持续6 d）。Morris水迷宫测试大鼠平均逃避潜伏期（AEL）,免疫组化和Western blotting法检测海马HMGB1和JNK的表达。结果: 与A组相比,B和D组大鼠造模后各时点AEL明显延长（P＜0.05）,C组大鼠第5天和第6天 AEL较B组相应时点明显缩短（P＜0.05）;B组和D组海马存在HMGB1大量胞浆、胞外释放情况（P＜0.05）,而C组海马区HMGB1胞浆、胞外释放无明显差异（P＞005）。4组大鼠海马总HMGB1表达水平比较差异无统计学意义（P＞0.05）,但B组和D组海马JNK表达水平增高（P＜0.05）。结论: 姜黄素能够改善AD大鼠的学习记忆能力,其机制可能与抑制HMGB1的胞浆、胞外释放及JNK的表达下调有关。     

运动对冠心病患者血浆纤溶活性的影响及其临床意义

为探讨冠心病患者血浆纤溶活性变化及其与冠脉病变程度的关系。本文比较了冠心病组和正常对照组在桨极量运动前后血浆组织型纤溶酶的激活物（ｔＰＡ）,纤溶酶原么物抑制剂－１（ＰＡＩ－１）活性的变化。及其与心肌缺血面积的相关性。结果显示：（１）运动前冠心组ｔＰＡ及ＰＡＩ－１活必闹于正常对照组（Ｐ〈０．０５）,运动后冠心病组ＰＡＩ０－１活性明显升高（Ｐ〈０．０５）,而ｔＰＡ活性水平明显下降（Ｐ〈０．０５）;（２     

Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain

Background: Neuropathic pain is characterized by hyperalgesia, allodynia and spontaneous pain. It often occurs as a result of injury to peripheral nerves, dorsal root ganglions (DRG), spinal cord, or brain. Recent studies have suggested that Toll-like receptor 4 (TLR4) might play a role in neuropathic pain. Methodology/Principal Findings: In this study, we investigated the role of TLR4 in a rat chronic constriction injury (CCI) model and explored the feasibility of treating neuropathic pain by inhibiting TLR4. Our results demonstrated that intrathecal siRNA-mediated suppression of TLR4 attenuated CCI-induced mechanical allodynia and thermal hyperalgesia through inhibiting the activation of NF-κB p65 and production of proinflammatory cytokines (e.g., TNF-α and IL-1β). Conclusions/Significance: These findings suggest that suppression of TLR4 mediated by intrathecally administered siRNA may be a new strategy for the treatment of neuropathic pain.     

冠心病介入治疗患者体外反搏的疗效探讨

目的探讨增强型体外反搏(enhancedexternalcouterpulsationEECP)对冠心病经皮冠状动脉介入治疗患者的疗效。方法经选择性冠状动脉造影确诊为冠心病且介入治疗成功的患者共469例,其中85例在药物治疗的基础上行体外反搏治疗(EECP组),另384例予单纯药物治疗(药物组)。临床随访6~72个月,部分行超声心动图和冠脉造影复查,比较两组随访病例临床终点事件、左室功能和造影结果的差异。结果(1)基线资料:对EECP组81例(95%)和药物组350例(91%)成功进行了随访,两组在临床资料、造影特征和介入治疗等方面差异均无统计学意义(P>0.05)。⑵临床终点事件:EECP组心绞痛复发率显著低于药物组(8·6%比17.4%,P<0.05);EECP组总的临床终点事件发生率明显低于药物组(18.5%比35.4%,P<0.01)。(3)超声心动图:两组基线室壁运动指数和左室射血分数相似,但复查时EECP组明显优于药物组(P<0.01)。⑷冠状动脉造影:两组再狭窄发生率差异无统计学意义P>0.05,但EECP组出现侧支循环患者数明显多于药物组(17.9%比5·1%,P<0.05),复查时病变血管参考内径[(3.29±0.61)mm比(3.06±0.50)mm,P<0.05]和支架内最小腔径[(3.02±0.59)mm比(2.67±0.62)mm,P<0.01]均显著大于药物组。结论对于介入治疗成功的冠心病患者,增强型体外反搏可减少心绞痛复发,改善预后和心功能,并可能有预防再狭窄的作用。     

Protective effect of R allele of PON1 gene on the coronary artery disease in the presence of specific genetic background

Background: Genetic susceptibility to CAD may be determined by polymorphic variants of genes encoding isoforms involved in the processes important in the pathogenesis of atherosclerosis, including lipids disorders. Participation of single polymorphic variants is relatively small, however its significance may increase in the presence of specific genetic or environmental background. Aim: The aim of the study was an evaluation a possible association between single polymorphic variants of PON1, APOE, ABCA1 and PPARA genes and CAD and looking for specific multigene genotype patterns which differentiate study groups. Materials and methods: We studied 358 subjects:178 patients with angiographically confirmed CAD and 180 blood donors without history of CAD. Polymorphisms were genotyped using PCR-RFLP method. Results: We observed statistically significant differences in the frequencies of R allele and R allele carriers of PON1 gene between CAD and controls. The distribution of genotypes and alleles of other analyzed genes did not differentiate the study groups, however the presence of specific genotypes (APOE– ɛ3ɛ3, ɛ3ɛ2, ABCA1 – AG, PPARA – GG) increased the protective effect of R allele. Conclusion: The present study revealed an independent protective association between carrier-state of PON1 R allele and CAD. This protective effect was especially strong in the presence of specific genotype arrangements of other analyzed genes.     

心脏瓣膜术联合冠状动脉旁路移植术治疗心脏瓣膜疾病患者的临床价值研究

目的:分析心脏瓣膜术联合冠状动脉旁路移植术治疗心脏瓣膜疾病患者的临床价值.方法:选取我院于2017年5月至2019年5月期间收治的80例心脏瓣膜病患者为研究对象,随机分为研究组和对照组,各40例.对比两组术后相关指标情况、手术前后心功能指标.结果:研究组呼吸机辅助通气时间、ICU监护时间以及住院时间均短于对照组(P<0...     

真武汤加味对冠心病心力衰竭患者左心功能的影响

目的：评价真武汤加味对冠心病心力衰竭患者左心功能的影响。方法：100例冠心病心力衰竭患者随机分为治疗组和对照组,各50例。对照组用西医常规药物治疗,治疗组用西医常规药物加真武汤加味治疗,于入院当天和入院第90天行二维超声心动图测量,计算左心室舒张末内径、左心室收缩末内径和左室射血分数,并抽血检查血浆N端脑钠肽前体水平的变化。结果：与治疗前比较,两组的左心室舒张和收缩末内径均显著缩小（均P〈0．01）,左心室射血分数均明显增加（均P〈0．01）,血浆N端脑钠肽前体水平均显著降低（均P〈0．01）,用药后治疗组各指标改善明显优于对照组（均P〈0．011。结论：西医常规药物加真武汤加味治疗可以显著改善冠心病心力衰竭患者的左心功能和心室重构。     

Death-inducing receptors and apoptotic changes in lymphocytes of patients with heart transplant vasculopathy

The specific role of lymphocyte apoptosis and transplant-associated atherosclerosis is not well understood. The aim of our study was to investigate the impact of T cell apoptotic pathways in patients with heart transplant vasculopathy. Amongst 40 patients with cardiac heart failure class IV who have undergone heart transplantation, 20 recipients with transplant-associated coronary artery disease (TACAD) and 20 with non-TACAD were investigated one year postoperative. Expression of CD95 and CD45RO, and annexin V binding were measured by FACS. Soluble CD95, sCD95 ligand (sCD95L), tumour necrosis factor receptor type 1 (sTNFR1), and histones were measured in the sera by ELISA. The percentage of cells expressing CD3 and CD4 was significantly reduced in TACAD as well as in non-TACAD patients as compared with control volunteers. Interestingly, the proportion of CD19+ (B cells) and CD56+ (NK) cells was increased in TACAD groups (versus non-TACAD; P < 0.01, and P < 0.001, respectively). In contrast to sCD95, the expression of CD95 (APO-1/Fas) and CD45RO (memory T cells), and sCD95L were significantly increased in non-TACAD and TACAD patients. T cell activation via CD95 with consecutive apoptosis was increased in both groups. The concentration of sTNFR1, IL-10 and histones was significantly elevated in sera from TACAD than non-TACAD patients, and in both groups than in healthy controls. These observations indicate that the allograft may induce a pronounced susceptibility of CD4+ T cells to undergo apoptosis and antibody-driven activation-induced cell death. This data may suggest a paradox immune response similar to that seen in patients with autoimmune diseases.     

单核细胞/高密度脂蛋白比值在冠心病诊断和预测预后的研究进展

绝大部分冠心病为冠状动脉粥样硬化所致,目前认为,动脉粥样硬化是一种慢性炎性反应疾病。单核细胞和高密度脂蛋白比值(MHR)是近年新兴的一种炎性反应标志物,其获取简单,检测价格低廉,与冠心病短期和长期的心血管事件发生率及病死率相关,可作为冠心病预后的预测因素。     

冠心病患者外周血T淋巴细胞PD-L1的表达及意义

目的研究程序性死亡配体-1（PD-L1）在冠心病患者外周血中T淋巴细胞上的表达及意义。方法按照WHO关于冠心病诊断标准,将实验分为稳定型心绞痛（SA）组（n=23）、急性冠脉综合征（ACS）组（n=21）和正常对照组（n=18）,三组均经冠状动脉造影证实。采集三组人群的外周血,用流式细胞技术及RT-PCR技术测定T淋巴细胞PD-L1蛋白及mRNA表达情况。结果与正常对照组比较,SA组和ACS组外周血T淋巴细胞PD-L1蛋白及mRNA表达水平均显著升高（P〈0.01）;但SA组与ACS组比较差异无统计学意义（P〉0.05）。结论冠心病患者外周血T淋巴细胞PD-L1表达上调,其可能在动脉粥样硬化斑块形成过程中起作用。     

Anti-inflammatory and antioxidant effects of curcumin on acute lung injury in a rodent model of intestinal ischemia reperfusion by inhibiting the pathway of NF-Kb

Objective: To investigate the anti-inflammatory and antioxidant effect of curcumin on lung lesion induced by intestinal ischemia reperfusion injury (IIR). Methods: Rats were divided into four groups: sham, intestinal IIR (IIR), 1 mg/kg of curcumin treatment group (1 mg/kg), and 5 mg/kg of curcumin treatment group (5 mg/kg). Curcumin was given respectively (1 mg/kg and 5 mg/kg) following the above doses. IIR was produced by 1 h of intestinal ischemia followed by 2 h of reperfusion. Rats were sacrificed at the end of reperfusion and lung tissues were collected for biochemical and histopathological examination in 4 groups. Lung tissues histology and bronchoalveolar lavage fluid (BALF) protein were assayed. Serum IL-6, lung superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The expression level of NF-κB and ICAM-1 (including immunohistochemical analysis and western blot analysis) were also measured. Results: Lung tissue injury induced by IIR was obviously observed through pathology and BALF protein. MPO activity, IL-6 level and ICAM-1 expression were significantly increased with the elevation of NF-κB, simultaneously, SOD activity was decreased. With Treatment of curcumin, pathology and BALF protein of lung tissue were improved clearly. Inflammatory indexes (MPO activity, IL-6 level and ICAM-1) were improved and antioxidant index (SOD activity) was enhanced paralleled with NF-κB. Conclusion: Using curcumin effectively prevented IIR-induced lung injury. Anti-inflammatory and antioxidant effects of curcumin could be observed by inhibiting the pathway of NF-κB.     

Genistein suppresses the inflammation and GSK-3 pathway in an animal model of spontaneous ovarian cancer

Background/aim Numerous studies show that cancer risk is reduced by consumption of soy-based foods containing genistein, but its effects on the glycogen synthase kinase-3 pathway (GSK-3) in ovarian cancer is unknown. Therefore, we tested the properties of genistein on inflammatory biomarkers and GSK-3 signaling pathways in the ovaries of old laying hens with ovarian cancer. Materials and methods A total of 300 laying hens were distributed into three groups as follows: group 1, animals fed a standard diet (comprising 22.39 mg of genistein/kg of diet); groups 2 and 3, animals fed a standard diet reconstituted with supplementation of 400 mg or 800 mg of genistein/kg of diet, respectively.Results Genistein modulated the inflammatory biomarkers by decreasing serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) compared with control (p < 0.001). Moreover, it upregulated insulin receptor substrate-1 (p-IRS-1) and protein kinase B (p-AKT), but downregulated GSK-3α and β after treatment. It acts in a dose-dependent manner. Conclusion Genistein exhibited an anticancer effect by reducing proinflammatory biomarkers levels and inhibiting GSK-3 expression in the ovaries of old laying hens. It is a potential candidate in the chemoprevention and/or treatment of ovarian cancer.     

Impact of diabetes on mortality and complications after coronary artery by-pass graft operation in patients with left main coronary artery disease

PurposeLeft main disease (LMD) is a severe form of coronary artery disease (CAD). Fifty percent of patients with LMD treated conservatively die within 3–5 years of diagnosis. The aim of the study was to assess the influence of type 2 diabetes on early and late (2-year) prognosis and the risk of complications after coronary artery by-pass graft (CABG) surgery in patients with LMD.Material/methodsWe enrolled 257 patients diagnosed with LMD. 169 (67%) underwent CABG, 19 (8%) percutaneous coronary intervention (PCI) without left main stem protection. 30 (12%) patients had CABG previously. Patients treated with CABG were divided into two groups – with and without diabetes. There were 43 (25.4%) patients with diabetes and 126 (74.6%) without diabetes.ResultsWe observed more complications with wound healing (40.5% vs. 12.8%, p < 0.001) and sternal dehiscence (23.8% vs. 4.0%, p < 0.001) after CABG in patients with diabetes. There were no differences in 7-day, 30-day, 3-month and 1-year mortality. 2-Year mortality was also similar in both groups (11.6% vs. 11.1%, p = 0.928). Patients with diabetes were more frequently hospitalized due to other reasons than angina (39.5% vs. 20.6%, p = 0.014).ConclusionsPatients with diabetes and LMD had more often complications with wound healing and sternal dehiscence after CABG than patients without diabetes. Type 2 diabetes did not influence early and late mortality in patients with LMD treated with cardiac surgery, but the presence of diabetes was associated with more frequent hospitalizations.