Thioredoxin-interacting protein promotes activation and inflammation of monocytes with DNA demethylation in coronary artery disease

Numerous studies have demonstrated that thioredoxin-interacting protein (TXNIP) expression of peripheral blood leucocytes is increased in coronary artery disease (CAD). However, the molecular mechanism of this phenomenon remained unclear. DNA methylation plays important roles in the regulation of gene expression. Therefore, we speculated there might be a close association between the expression of TXNIP and methylation. In this study, we found that compared with controls, DNA methylation at cg19693031 was decreased in CAD, while mRNA expressions of TXNIP and inflammatory factors, NLRP3, IL-1β, IL-18, were increased. Methylation at cg19693031 was negatively associated with TXNIP expression in the cohort, THP-1 and macrophages/foam cells. Furthermore, Transwell assay and co-cultured adhesion assay were performed to investigate functions of TXNIP on the migration of THP-1 or the adhesion of THP-1 on the surface of endothelial cells, respectively. Notably, overexpressed TXNIP promoted the migration and adhesion of THP-1 cells and expressions of NLRP3, IL-18 and IL-1β. Oppositely, knock-down TXNIP inhibited the migration and adhesion of THP-1 and expressions of NLRP3, IL-18. In conclusion, increased TXNIP expression, related to cg19693031 demethylation orientates monocytes towards an inflammatory status through the NLRP3 inflammasome pathway involved in the development of CAD.     

Association between the risk of coronary artery disease in South Asians and a deletion polymorphism in glutathione S-transferase M1

Background: The aim of the present study was to evaluate whether or not an elevated ischaemia-modified albumin (IMA) level provides any additional prognostic information to the validated Thrombolysis In Myocardial Infarction (TIMI) risk score in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Methods: One hundred seven consecutive STEMI patients treated with primary PCI were included. The incidence of 30-day death was the prespecified primary end point. Serum IMA was measured immediately at hospital arrival. Results: The incidence of the primary end point was 6.5%. A significant predictive value of IMA in relation to the primary end point was indicated by an area under the ROC curve of 0.71 (p = 0.01). In the multivariate analysis, increased IMA remained a significant predictor of the primary end point after adjustment for TIMI risk predictors (p = 0.019). The area under the ROC curve for the TIMI risk score was 0.68 (p = 0.03). The addition of IMA to the TIMI risk score did not improve its prognostic value (area under the ROC curve 0.60, p = 0.25). Conclusion: IMA levels obtained at admission are a powerful indicator of short-term mortality in STEMI patients treated with primary PCI, but do not seem to be a marker that adds prognostic information to the validated STEMI TIMI risk score.     

冠脉不同程度狭窄猪血浆骨保护素变化的影响研究

目的:冠心病的发病率越来越高,成为临床上常见的心血管疾病。冠心病的发生、发展与冠状动脉病变程度直接相关。通过手术引起冠脉狭窄,探讨冠脉狭窄与骨保护素(OPG)的相关性,从而为临床冠心病的预测提供理论依据。方法:(1)20头巴马小型猪,在胸腔镜直视下手术丝线永久性结扎左前降支近端建立轻度(狭窄程度20-49%)、中度(狭窄程度50-69%)和重度(狭窄程度≥70%)狭窄的冠状动脉狭窄模型;(2)各组小型猪分别在其手术处理前后1 min留取静脉血和分离血浆,测定骨保护素的含量。结果:(1)手术对各组小型猪血浆OPG的影响差异无统计学意义(P0.05),同时,各组之间冠脉狭窄模型猪手术后血浆OPG的浓度较对照组升高,但无统计学差异(P0.05)。结论:(1)手术作为一种应激性损伤,导致OPG升高。(2)骨保护素与冠状动脉硬化和血管钙化有关,但与没有动脉硬化和钙化引起的的冠脉狭窄无关。     

清醒狗短暂缺血心肌复灌注时舒缩功能的变化

在狗的心脏上装入微超声探头和高精度微压力传感器,手术后两星期,在清醒状态下给予左冠状动脉旋支阻断三分钟。在复灌注过程中,观察到血液动力学指标与收缩期心室壁厚度(WT)迅速恢复正常;但在 dWT/dt—WT 环形图上出现舒张早期异常相,其形状与缺血过程不同。低氧和急遽冠状动脉过度充盈可以产生此种异常图形。我们推测,心肌缺血可能促使一些产物的形成,复灌注时它使冠脉过度舒张,冠脉灌注增加,从而造成舒张早期急遽充盈而形成了此种异常的形图。     

PCI术后是否抗凝治疗的临床疗效比较

目的：研究PCI术后是否应用依诺肝素抗凝治疗对患者临床疗效的影响。方法：于2011年5月至2012年1月间,连续入选在我院行冠状动脉造影并置入了支架的患者158例,将符合标准的患者随机分为非抗凝组或抗凝组两组各79名。非抗凝组术后常规应用阿司匹林和氯吡格雷。抗凝组术后加用依诺肝素。对入选患者进行院内随访记录其主要心脏不良事件及出血事件。结果：支架植入成功率100%。术后抗凝组113处病变共置入支架135枚;非抗凝组109处病变置入支架115枚。院内随访：主要心脏不良事件和严重出血差异无统计学意义。小出血事件抗凝组多于非抗凝组（P=0.007）。结论：冠状动脉支架置入术后非抗凝治疗组缺血不良事件发生率较抗凝组无明显增加,小出血并发症明显减少。该研究结果表明,对PCI术无特殊并发症的患者术后无需常规抗凝治疗。     

Genetic information improves the prediction of major adverse cardiovascular events in the GENEMACOR population

The inclusion of a genetic risk score (GRS) can modify the risk prediction of coronary artery disease (CAD), providing an advantage over the use of traditional models. The predictive value of the genetic information on the recurrence of major adverse cardiovascular events (MACE) remains controversial. A total of 33 genetic variants previously associated with CAD were genotyped in 1587 CAD patients from the GENEMACOR study. Of these, 18 variants presented an hazard ratio >1, so they were selected to construct a weighted GRS (wGRS). MACE discrimination and reclassification were evaluated by C-Statistic, Net Reclassification Index and Integrated Discrimination Improvement methodologies. After the addition of wGRS to traditional predictors, the C-index increased from 0.566 to 0.572 (p=0.0003). Subsequently, adding wGRS to traditional plus clinical risk factors, this model slightly improved from 0.620 to 0.622 but with statistical significance (p=0.004). NRI showed that 17.9% of the cohort was better reclassified when the primary model was associated with wGRS. The Kaplan-Meier estimator showed that, at 15-year follow-up, the group with a higher number of risk alleles had a significantly higher MACE occurrence (p=0.011). In CAD patients, wGRS improved MACE risk prediction, discrimination and reclassification over the conventional factors, providing better cost-effective therapeutic strategies.     

不同麻醉方式对老年冠心病患者围术期血流动力学及ECG的影响

目的：探讨对择期腹部手术的老年冠心病患者心脏血流动力学及心脏电活动影响较小的麻醉方式。方法：133例择期腹腔手术的老年冠心病患者随机分为硬膜外麻醉组（EA）,全麻组（GA）和腰-硬联合麻醉组（CSEA）。术中连续监测,分时段记录平均动脉压（MAP）、心率（HR）、血氧饱和度（SaO2）及异常心电图,比较3组组间及组内差异。结果：麻醉后15 min和麻醉后30 min,GA组的SaO2明显高于EA组（P〈0.05）。麻醉后15min、30 min和60 min CSEA组MAP值比EA组明显升高（P〈0.05）;麻醉后30 min,CSEA组的HR比EA组明显升高（P〈0.05）;麻醉后15 min和30 min,CSEA组的SaO2比EA组明显升高（P〈0.05）。组内比较,EA组麻醉后15min、30 min、60 min,MAP、HR、SaO2三个指标均比麻醉前明显降低（P〈0.05）,GA组和CSEA组前后比较差异不明显（P〉0.05）。异常ECG,组间比较,GA组和CSEA组ST-T改变发生率在麻醉后15 min、30 min、60 min、术毕时均明显低于EA组（P〈0.05,P〈0.01）,GA组和CSEA组心律失常发生率在麻醉后15 min、30 min、60 min均明显低于EA组（P〈0.05,P〈0.01）;组内比较,GA组和CSEA组的ST-T改变和心律失常发生率在麻醉后15 min、30min、60 min、术毕时均明显低于麻醉前（P〈0.05,P〈0.01）。结论：老年冠心病患者腹腔手术时全麻和腰-硬联合麻醉术中血流动力学较稳定,心电异常发生率较小。     

冠状动脉介入治疗对冠心病患者Caspase-3,9 水平的影响

目的:通过对冠心病患者经皮冠状动脉介入治疗(PCI)前后血清Caspase-3,9水平变化的观察,探讨冠状动脉介入治疗对冠心病患者血清Caspase-3,9水平的影响。方法:冠状动脉介入组(PCI组)30例和单纯造影组(CAG组)29例,在术前0.5h,术后3h,术后6h,术后12h,术后24h,术后48h分别测定血清Caspase-3,9水平。结果:CAG组术前与术后的血清Caspase-3,9水平差异均无统计学意义,PCI组术后3h、6h的Caspase-3水平较术前0.5h均有降低趋势,差异均有统计学意义(P<0.05),PCI组术后48h的Caspase-9水平与术后3h、6h相比均有升高趋势,差异均有统计学意义(P<0.05)。结论:PCI术后狭窄或闭塞的冠状动脉血管重新恢复血供,血清中Caspase-3,9水平在PCI术后先降低后又逐渐升高,提示再灌注后可出现细胞的凋亡程度加重,血清中Caspase-3,9的水平可作为心肌再灌注损伤后细胞凋亡程度的评估指标并可作为诊断临床症状不典型的再灌注损伤的一个指标。PCI术可有效改善心肌血供,减少因术前缺血缺氧造成的细胞凋亡,但PCI术后再灌注损伤可进一步加重细胞凋亡。     

急性冠脉事件发病特点及院前急救对策

目的分析我院急诊科对急性冠脉事件包括急性心肌梗死（AMI）和不稳定型心绞痛（UAP）的院前急救情况,就其存在的问题提出对策。方法回顾性分析1989～2010年救治的急性冠脉事件患者166例临床资料,其中AMI患者72例,UAP患者94例。结果急性冠脉事件发生率占急性心脏事件的48．8％,其院前急救率为31．3％（52／166）,院前抢救成功率为82．69％（44／52）。结论（1）急性冠脉事件的院前急救率仍低,主要与患者及其家属不了解急性冠脉综合征的发病先兆和表现等相关知识以及呼救意识有关,因此加强相关知识的群众性普及教育迫在眉睫。（2）缩短出诊半径、加强医务人员对急诊处理特别是院前处理急性冠脉事件知识的培训、完善院前急救设备,是提高急性冠脉事件院前抢救成功率的保障。     

Retracted: Downregulated microRNA-224 aggravates vulnerable atherosclerotic plaques and vascular remodeling in acute coronary syndrome through activation of the TGF-β/Smad pathway

Recent studies have shown that circulating microRNAs (miRNA) play a critical role in diagnosing acute coronary syndrome (ACS). This study aims to investigate the effect of miR-224 on atherosclerotic plaques forming and vascular remodeling in ACS and its relationship with TGF-β/Smad pathway. Myocardial infarction (MI) rat model was established and lentivirus vector of miR-224 inhibitor was prepared for investigating the effect of downregulated miR-224 on the contents of nitric oxide (NO) and endothelin-1 (ET-1), blood lipid levels and inflammatory factor levels in serum as well as the TGF-β/Smad pathway. The rats suffering from MI had decreased survival rates and exhibited reduced levels of NO, high-density lipoprotein cholesterol, and lumen diameter, and Smad7 messenger RNA (mRNA) and protein expression; while had significantly increased ratio of heart weight or body weight, levels of ET-1, inflammatory factors, blood lipid indexes, vascular remodeling indexes, collagen volume fraction, vulnerable atherosclerotic plaque area, VCAM-1 and MMP-2 protein expression, TGF-β, Smad2, Smad3, and Smad4 mRNA and protein expression. After inhibiting the TGF-β/Smad pathway, the rats suffering from MI showed notably opposite trend. In conclusion, downregulation of miR-224 expression promotes the formation of vulnerable atherosclerotic plaques and vascular remodeling in ACS through activation of the TGF-β/Smad pathway. Therefore, this study provides a new therapeutic target for ACS.