Glutaredoxin-2 Is Required to Control Oxidative Phosphorylation in Cardiac Muscle by Mediating Deglutathionylation Reactions

Glutaredoxin-2 (Grx2) modulates the activity of several mitochondrial proteins in cardiac tissue by catalyzing deglutathionylation reactions. However, it remains uncertain whether Grx2 is required to control mitochondrial ATP output in heart. Here, we report that Grx2 plays a vital role modulating mitochondrial energetics and heart physiology by mediating the deglutathionylation of mitochondrial proteins. Deletion of Grx2 (Grx2^−/−) decreased ATP production by complex I-linked substrates to half that in wild type (WT) mitochondria. Decreased respiration was associated with increased complex I glutathionylation diminishing its activity. Tissue glucose uptake was concomitantly increased. Mitochondrial ATP output and complex I activity could be recovered by restoring the redox environment to that favoring the deglutathionylated states of proteins. Grx2^−/− hearts also developed left ventricular hypertrophy and fibrosis, and mice became hypertensive. Mitochondrial energetics from Grx2 heterozygotes (Grx2^+/−) were also dysfunctional, and hearts were hypertrophic. Intriguingly, Grx2^+/− mice were far less hypertensive than Grx2^−/− mice. Thus, Grx2 plays a vital role in modulating mitochondrial metabolism in cardiac muscle, and Grx2 deficiency leads to pathology. As mitochondrial ATP production was restored by the addition of reductants, these findings may be relevant to novel redox-related therapies in cardiac disease.     

Protein O-GlcNAcylation and Cardiovascular (Patho)physiology

Our understanding of the role of protein O-GlcNAcylation in the regulation of the cardiovascular system has increased rapidly in recent years. Studies have linked increased O-GlcNAc levels to glucose toxicity and diabetic complications; conversely, acute activation of O-GlcNAcylation has been shown to be cardioprotective. However, it is also increasingly evident that O-GlcNAc turnover plays a central role in the delicate regulation of the cardiovascular system. Therefore, the goals of this minireview are to summarize our current understanding of how changes in O-GlcNAcylation influence cardiovascular pathophysiology and to highlight the evidence that O-GlcNAc cycling is critical for normal function of the cardiovascular system.     

Activated Platelets Interfere with Recruitment of Mesenchymal Stem Cells to Apoptotic Cardiac Cells via High Mobility Group Box 1/Toll-like Receptor 4-mediated Down-regulation of Hepatocyte Growth Factor Receptor MET

Recruitment of mesenchymal stem cells (MSC) following cardiac injury, such as myocardial infarction, plays a critical role in tissue repair and may contribute to myocardial recovery. However, the mechanisms that regulate migration of MSC to the site of tissue damage remain elusive. Here, we demonstrate in vitro that activated platelets substantially inhibit recruitment of MSC toward apoptotic cardiac myocytes and fibroblasts. The alarmin high mobility group box 1 (HMGB1) was released by platelets upon activation and mediated inhibition of the cell death-dependent migratory response through Toll-like receptor (TLR)-4 expressed on the MSC. Migration of MSC to apoptotic cardiac myocytes and fibroblasts was driven by hepatocyte growth factor (HGF), and platelet activation was followed by HMGB1/TLR-4-dependent down-regulation of HGF receptor MET on MSC, thereby impairing HGF-driven MSC recruitment. We identify a novel mechanism by which platelets, upon activation, interfere with MSC recruitment to apoptotic cardiac cells, a process that may be of particular relevance for myocardial repair and regeneration.     

MRI and cardiac implantable electronic devices; current status and required safety conditions

Magnetic resonance imaging (MRI) has evolved into an essential diagnostic modality for the evaluation of all patient categories. This gain in popularity coincided with an increase in the number of implanted cardiac implantable electronic devices (CIEDs). Therefore, questions arose with regard to the MRI compatibility of these devices. Various investigators have reported the harmless performance of MRI in patients with conventional (non-MRI conditional) devices. The recently published European Society of Cardiology (ESC) guidelines on cardiac pacing and cardiac resynchronisation therapy (CRT) indicate that MRI can be safely performed in patients with an implanted pacemaker or ICD (MRI conditional or not), as long as strict safety conditions are met. This is a major modification of the former general opinion that patients with a pacemaker or ICD were not eligible to undergo MRI. This review paper attempts to elucidate the current situation for practising cardiologists by providing a clear overview of the potential life-threatening interactions and discuss safety measures to be taken prior to and during scanning. An overview of all available MRI conditional devices and their individual restrictions is given. In addition, an up-to-date safety protocol is provided that can be used to ensure patient safety before, during and after the scan.Key points• Historically, MRI examination of patients with a CIED has been considered hazardous.• Ongoing advances in technology and increasing usage of MRI in clinical practice have led to the introduction of MRI conditional CIEDs and to more lenient regulations on the examination of patients with non-conditional CIEDs.• MRI investigations can be performed safely in selected patients when adhering to a standardised up-to-date safety protocol.     

实时三维超声心动图诊断心脏多发性粘液瘤5例并文献分析

目的：探讨实时三维超声心动图对心脏多发性粘液瘤诊断和术前风险评估及手术方式选择的临床意义。方法：回顾性分析我院2007年1月至2012年12月收治的经手术病理确诊为心脏多发性粘液瘤5例患者的二维超声心动图（two-dimensionale echocardiography,2DE）、实时三维超声心动图（real-time three-dimensional echocardiography,RT-3DE）声像图特征,并结合相关文献进行分析。结果：5例患者的超声心动图均在心腔内探及多个活动性团块,各团块均与一蒂相连接,RT-3DE较2DE能准确显示粘液瘤整体形态、位置及与周围组织清晰的界限,并定量测定其大小。结论：RT-3DE弥补了2DE不能显示粘液瘤立体形态图像的缺点,可更为准确、简便、快捷地对心脏多发性粘液瘤做出诊断,并为术前风险评估及手术方式的选择提供了更可靠的依据。     

Potential impact of silymarin in combination with chlorogenic acid and/or melatonin in combating cardiomyopathy induced by carbon tetrachloride

The aim of this study was to investigate the effective role of silymarin either alone or in combination with chlorogenic acid and/or melatonin against the toxic impact of carbon tetrachloride (CCl4) induced cardiac infarction. CCl4 (l.2 ml/kg body weight) was administered as a single dose intraperitoneally. The results revealed that the administration of silymarin alone or in combination with chlorogenic acid (CGA) and/or melatonin for 21 consecutive days, 24 h after CCl4 injection to rats, markedly ameliorated the increases in serum markers of cardiac infarction, including troponin T and creatine kinase-MB (CK-MB), as well as increases in the pro-inflammatory biomarkers, including interleukin-6 (IL-6), interferon-γ (IFN-γ) in serum and tumor necrosis factor-α (TNF-α) and C-reactive protein in cardiac tissue compared to CCl4 intoxicated rats. The used agents also successfully modulated the alteration in vascular endothelial growth factor (VEGF) in serum and the oxidative DNA damage and the increase in the apoptosis marker caspase 3 in cardiac tissue in response to CCl4 toxicity. The present biochemical results are supported by histo-pathological examination. The current results proved that treatment with silymarin in combination with CGA and melatonin was the most effective one in ameliorating the toxicity of CCl4 induced cardiac damage and this may support the use of this combination as an effective drug to treat cardiac damage induced by toxic agents.     

Mapping ecosystem services: The supply and demand of flood regulation services in Europe

Ecosystem services (ES) feature highly distinctive spatial and temporal patterns of distribution, quantity, and flows. The flow of ecosystem goods and services to beneficiaries plays a decisive role in the valuation of ES and the successful implementation of the ES concept in environmental planning. This is particularly relevant to regulating services where demands emerge often spatially separated from supply. However, spatial patterns of both supply and demand are rarely incorporated in ES assessments on continental scales. In this paper, we present an ES modeling approach with low data demand, fit to be employed in scenario analysis and on multiple scales. We analyze flood regulation services at a European scale by explicitly addressing the spatial distribution of ES demand. A flood regulation supply indicator is developed based on scenario runs with a hydrological model in representative river catchments, incorporating detailed information on land, cover, land use and management. Land use sensitive flood damage estimates in the European Union (EU) are employed to develop a spatial indicator for flood regulation demand. Findings are transferred to the EU territory to create a map of the current supply of flood regulation and the potential supply under conditions of natural vegetation. Regions with a high capacity to provide flood regulation are mainly characterized by large patches of natural vegetation or extensive agriculture. The main factor limiting supply on a continental scale is a low water holding capacity of the soil. Flood regulation demand is highest in central Europe, at the foothills of the Alps and upstream of agglomerations. We were able to identify areas with a high potential capacity to provide flood regulation in conjunction with land use modifications. When combined with spatial patterns of current supply and demand, we could identify priority areas for investments in ES flood regulation supply through conservation and land use planning. We found that only in a fraction of the EU river catchments exhibiting a high demand, significant increases in flood regulation supply are achievable by means of land use modifications.     

急性心肌梗死患者冠脉搭桥术前中性粒细胞-淋巴细胞比率与 围术期心肌损伤相关分析*

摘要目的：探讨急性心肌梗死患者冠脉搭桥（CABG）术前中性粒细胞- 淋巴细胞比率（NLR）与围术期心肌损伤的关系,为临床 CABG 围术期心肌保护提供参考依据。方法：选取2012 年1 月至2012年6 月于首都医科大学附属北京安贞医院因急性心肌梗死 接受冠脉搭桥手术（CABG）患者210 例,收集术前血常规及术后肌钙蛋白I（cTnI）及肌酸激酶同工酶（CK-MB）,计算NLR;采用 四分位法根据NLR 水平将患者分为四组,比较各组cTnI 及CK-MB 峰值,多元逐步回归分析NLR 与cTnI 及CK-MB 峰值的相 关性。结果：随着NLR 水平升高,高血压病史和射血分数＜50%患者比例逐渐增多;白细胞计数、术后CK-MB 及cTnI峰值、术后 血肌酐值均逐渐增加;多元逐步回归分析显示,NLR、WBC分别与cTnI 峰值呈正相关（r=0.526,r=0.186,P<0.05）。结论：术前 NLR、WBC 与cTnI 峰值呈正相关,NLR 可能是反应急性心肌梗死患者冠脉搭桥围术期心肌损伤的良好标志物。     

血清标志物联合检测在急性冠状动脉综合征诊断中的应用

目的:探讨血清cTnⅠ、CK-MB、MYO及BNP联合检测在急性冠状动脉综合征诊断中的临床价值。方法:选择临床及冠状动脉造影明确诊断的ACS患者76例,稳定性心绞痛患者32例,同期选择35例健康体检者作实验对照组;应用免疫化学发光法分别检测患者血清中cTnⅠ、CK-MB、MYO及BNP水平,采用受试者工作特征曲线(ROC)评价各指标的敏感度、特异度,并分析4项指标联合检测的诊断价值。结果:ACS组血清cTnⅠ、CK-MB、MYO及BNP水平分别为(9.27±7.25)μg/L、(239.50±213.27)ng/ml、(37.06±21.60)ng/ml、(632.11±293.20)pg/ml;AS组分别为(1.32±0.57)μg/L、(63.34±31.02)ng/ml、(19.48±8.04)ng/ml、(125.20±6.57)pg/ml;对照组为(0.17±0.06)μg/L、(30.02±15.23)ng/ml、(14.06±3.19)ng/ml、(47.52±21.30)pg/ml;ACS组患者血清cTnⅠ、CK-MB、MYO及BNP水平及阳性率均高于SA组和健康对照组,组间差异有统计学意义(P0.05);cTnⅠ的ROC曲线下面积(AUC)为(0.917±0.025),高于BNP曲线下面积(0.823±0.031)(P=0.037);4项指标联合检测ACS患者的敏感度(92.3%),高于单项检测86.0%(P0.05)。结论:检测血清cTnⅠ、CK-MB、MYO及BNP对于判定心肌缺血和损伤程度有重要价值,各项指标之间有互补作用,联合检测可为ACS早期诊断提供参考依据。     

血压晨峰与原发性高血压患者心律失常及心肌缺血的关系

目的:探讨血压晨峰与原发性高血压患者心律失常及心肌缺血的相关关系及其临床意义。方法:选取2011年1月至2013年1月原发性高血压患者168例,根据动态血压结果,将血压晨峰≥23.6mmHg或23.6mmHg分成A组(晨峰组)79例与B组(非晨峰组)89例,所有患者均同步进行24 h动态心电图和动态血压监测,比较两组心律失常与心肌缺血发生情况。结果:两组患者的一般临床情况具有可比性。与B组比较,A组的高血压患者更易发生频发房性早搏、房速、频发室性早搏和室速等心律失常情况,差异有统计学意义(P0.05)。A组患者发生心律失常总数明显高于B组(=52.19,r=0.552,P0.001)。与B组比较,A组的高血压患者容易发生ST段改变,差异有统计学意义(P0.05);ST-T改变和T波改变两组之间差异无统计学意义(P0.05)。A组患者发生心肌缺血的情况明显高于B组(=10.05,r=0.213,p=0.0015)。结论:原发性高血压患者若出现血压晨峰提示心律失常和心肌缺血的发生率增加,尤其是房性早搏的发生率明显升高。血压晨峰与患者的心律失常和心肌缺血关系密切,具有临床指导意义。