Human C-reactive protein gene polymorphism and metabolic syndrome are associated with premature coronary artery disease

The aim of this study was to investigate the association between C-reactive protein (CRP) gene polymorphism and metabolic syndrome (MetS) with premature coronary artery disease (PCAD). 116 patients with PCAD (58 with MetS and 58 without MetS) and 119 controls were included in the study. CRP gene + 1059 G>C polymorphism was analyzed by polymerase chain reaction. Serum hs-CRP was measured using high-sensitivity enzyme-linked immunosorbent assay. Carriers of C allele of the CRP + 1059 G>C polymorphism had 3.37 fold increased risk to develop MetS in patients with PCAD. In addition CRP gene and hs-CRP levels were independent risk factors for PCAD and MetS. The present study provides new evidence that the presence of CRP + 1059 G>C polymorphism and hs-CRP levels are independent determinants of PCAD and MetS in Egyptians. The results of our study suggest a synergistic effect of CRP C allele with classical risk factors such as hypertension, obesity, dyslipidemia and MetS.     

Chronotherapy in Coronary Heart Disease: Comparison of Two Nitrate Treatments

The purpose of this study was to assess the ischemic burden and the hemodynamic changes during daily activities in patients with coronary heart disease. Three exercise tests were performed during the day (10:00 a.m., 2:00 p.m., 6:00 p.m.), recording ST-segment depression, pulmonary artery pressure, pulmonary wedge pressure, and cardiac output as well as heart rate and systemic blood pressure during placebo and nitrate therapy. With placebo as well as nitrate therapy there was a gradual increase of ischemia and preload and a decrease of cardiac output during the day. High nitrate concentrations led to a significant reduction of both preload and ST depression with a marked circadian phase dependency of cardiovascular effects.     

Circadian Variation of Cardiac Performance in Coronary Heart Disease

To study the circadian variation of cardiac performance in patients with coronary heart disease, three exercise tests on a bicycle crgometer were performed during the active part of the day (10 a.m., 2 p.m. and 6 p.m.), recording ST-segment depression and pulmonary capillary wedge pressure. Ten male patients with angiographically documented coronary heart disease underwent bicycle ergometry during placebo and during nitrate therapy (placebo controlled, double-blind crossover 2 × 20 mg IS-5-MN and 1 × 120 mg ISDN sustained release). During placebo as well as during nitrate therapy there was a gradual decrease of cardiac performance during the day, documented by the increase in ST-depression and pulmonary capillary wedge pressure at equal work loads. High nitrate concns led to a significant reduction of both ST-depression and preload with a marked circadian-phase dependency of cardiovascular effects.     

Recovery after Shift Work: Relation to Coronary Risk Factors in Women

Shift work increases the risk for developing cardiovascular disease. There is, however, little knowledge of what aspects of shift scheduling that are detrimental and what characteristics promote good health. The aim of the present study was to evaluate whether coronary risk factors deteriorate after a hard work period and whether recovery, in the form of a week off, was sufficient to improve them. A total of 19 women worked an extremely rapidly rotating and clockwise shift schedule at a paper and pulp factory. They underwent two health examinations, one at the end of the work period and one after the week off. In addition, the women were divided into a tolerant and a vulnerable group, depending on their satisfaction with their work hours. Most risk factors did not change, but total cholesterol and low‐density lipoprotein (LDL)‐cholesterol were lower after the working period than after the week‐off. In addition, vulnerable women had higher levels of total cholesterol and a higher ratio of total cholesterol/high‐density lipoprotein (HDL) than tolerant ones. In conclusion, the finding that a week‐off worsens cholesterol levels was against our hypothesis and suggests further studies on how activities/responsibilities outside the workplace affect shift‐working women. It was also shown that susceptible shift workers had worse lipid profiles.     

Humanization of Antibodies Using Heavy Chain Complementarity-determining Region 3 Grafting Coupled with in Vitro Somatic Hypermutation

A method for simultaneous humanization and affinity maturation of monoclonal antibodies has been developed using heavy chain complementarity-determining region (CDR) 3 grafting combined with somatic hypermutation in vitro. To minimize the amount of murine antibody-derived antibody sequence used during humanization, only the CDR3 region from a murine antibody that recognizes the cytokine hβNGF was grafted into a nonhomologous human germ line V region. The resulting CDR3-grafted HC was paired with a CDR-grafted light chain, displayed on the surface of HEK293 cells, and matured using in vitro somatic hypermutation. A high affinity humanized antibody was derived that was considerably more potent than the parental antibody, possessed a low pm dissociation constant, and demonstrated potent inhibition of hβNGF activity in vitro. The resulting antibody contained half the heavy chain murine donor sequence compared with the same antibody humanized using traditional methods.     

Tbx18 regulates development of the epicardium and coronary vessels

The epicardium and coronary vessels originate from progenitor cells in the proepicardium. Here we show that Tbx18, a T-box family member highly expressed in the proepicardium, controls critical early steps in coronary development. In Tbx18^−/− mouse embryos, both the epicardium and coronary vessels exhibit structural and functional defects. At E12.5, the Tbx18-deficient epicardium contains protrusions and cyst-like structures overlying a disorganized coronary vascular plexus that contains ectopic structures resembling blood islands. At E13.5, the left and right coronary stems form correctly in mutant hearts. However, analysis of PECAM-1 whole mount immunostaining, distribution of SM22α^lacZ/+ activity, and analysis of coronary vascular casts suggest that defective vascular plexus remodeling produces a compromised arterial network at birth consisting of fewer distributing conduit arteries with smaller lumens and a reduced capacity to conduct blood flow. Gene expression profiles of Tbx18^−/− hearts at E12.5 reveal altered expression of 79 genes that are associated with development of the vascular system including sonic hedgehog signaling components patched and smoothened, VEGF-A, angiopoietin-1, endoglin, and Wnt factors compared to wild type hearts. Thus, formation of coronary vasculature is responsive to Tbx18-dependent gene targets in the epicardium, and a poorly structured network of coronary conduit vessels is formed in Tbx18 null hearts due to defects in epicardial cell signaling and fate during heart development. Lastly, we demonstrate that Tbx18 possesses a SRF/CArG box dependent repressor activity capable of inhibiting progenitor cell differentiation into smooth muscle cells, suggesting a potential function of Tbx18 in maintaining the progenitor status of epicardial-derived cells.     

中国汉族人群CXCR2基因＋1235C/T多态与急性冠脉综合征的关联研究

目的：炎症反应在动脉粥样斑块变化的病理过程中发挥着重要的作用。本研究探讨CXCR2基因＋1235 C/T单核苷酸多态与中国汉族人群急性冠脉综合征发病的相关关系。方法：本研究采用聚合酶链反应-限制性片段长度多态性方法对675例急性冠脉综合征的患者和636例对照组进行检测,分析CXCR2基因＋1235 C/T单核苷酸多态的基因型和等位基因频率的分布情况,同时收集济南军区总医院心内科经冠脉造影证实为阳性的急性冠脉综合征患者360例及对照者360例,对上述关联分析的结果进行复制实验的印证。结果：CXCR2基因＋1235 C/T单核苷酸多态三种基因型（CC型,CT型和TT型）在急性冠脉综合征组分布频率分别为39.3%,45.3%和15.1%,在对照组分别为41.7%,47.2%和11.1%,CXCR2基因＋1235 C/T基因型和等位基因频率对照组和急性冠脉综合征组之间存在统计学差异（P〈0.05）。Logistic回归校正性别、年龄、体重指数、吸烟、高血压、高脂血症、糖尿病等冠心病的易患因素后,CXCR2基因＋1235 C/T多态与急性冠脉综合征的发病存在相关关系（P〈0.05）。结论：CXCR2基因＋1235 C/T多态与急性冠脉综合征发病存在相关关系,CXCR2基因＋1235 C/T多态可能是中国汉族人群急性冠脉综合征发病的独立危险因子。     

同型半胱氨酸与冠心病

随着社会的进步以及人类生活水平的提高,冠心痛的发病率也逐年提高,目前已经成为全球死亡率最高的疾病之一,同时医学水平的不断发展也使得人们对冠心病有了更进一步的研究.近年来同型半胱氨酸越来越受到人们的关注,众多研究表明,高同型半胱氨酸血症是冠心痛的独立危险因子,可以影响冠心病的严重程度及预后.但是迄今为止,同型半胱氨酸在冠心病发病中的确切机制尚不完全明确,认为主要与血管内皮损伤、血管平滑肌细胞增殖凋亡、破坏凝血纤溶系统、影响糖、蛋白质、脂质代谢等方面有关.针对高同型半胱氨酸血症的治疗,对于改善冠心病患者的预后有一定疗效.因此,本文就同型半胱氨酸冠心痛的关系作一综述,从而为临床更好的防治冠心痛提供相关的资料.     

动态心电图ST-T 改变诊断冠心病的临床价值研究

目的:探讨心电图ST-T的动态改变对临床诊断冠心病的实用价值。方法:选取2013年10月~2015年10月在我院诊断治疗的有ST-T段改变的患者,观察并记录所有患者的心电图状态,并重点监测ST-T改变的动态情况,并回归性分析及对比检测结果。结果:心电图ST-T改变有动态变化率的冠心病确诊率为67.9%,明显高于无动态变化组32.3%的确诊率。两组确诊率具有统计学意义(P0.05)。结论:心电图有动态改变的ST-T段改变能提高患者冠心病的临床确诊率,值得进一步推广应用。     

SPA患者循环EPCs及SDF-1-alpha与冠状动脉侧支循环的相关性分析

目的：研究冠状动脉严重狭窄稳定型心绞痛(Stable angina pectoris, SPA)患者循环内皮祖细胞（endothelial progenitor cells, EPCs）及基质细胞衍生因子（SDF）-1-alpha与冠状动脉侧支循环（CCC）形成的相关性,以期为治疗冠心病提供新的思路。方法：选择 2012 年8 月到2014 年12月在我院就诊的88 例冠状动脉严重狭窄的稳定型心绞痛患者（CCC 良好40 例、不良48 例）,均采集 外周血测定EPC 数量、体外生成血管能力,并用ELISA 法检测其血浆SDF-1alpha 水平,采用直线相关和Pearson 检验分析CCC良好 与不良者各指标间及与CCC 分级的相关性;将所有入选病例随机分为6 组,并分离外周血单个核细胞并分别加入不同的培养 液,培养7 天后体外测定EPCs 数量以及生成血管的能力,并通过ELISA 法检测培养液上清中VEGF 的蛋白水平。结果：CCC 不 良组EPCs 数量、体外生成血管能力及SDF-1-alpha水平均明显低于CCC 良好组（P<0.05）。体外生成血管能力、循环EPCs 数量以及 SDF-1alpha水平均与CCC分级呈现显著的正相关性（r =0.72、0.67、0.79,均P<0.05）;循环EPCs 数量、SDF-1alpha水平以及体外生成血 管能力亦均呈现显著正相关性（r =0.78、0.62,均P<0.05）。与PBS、SDF-1alpha+ AMD3100 及SDF-1alpha+ KI8751 干预物质比较,SDF-1琢 能够呈剂量依赖性的明显提高EPCs 数量、增强其体外生成血管的能力及VEGF水平（P<0.05）。结论：冠状动脉严重狭窄稳定型 心绞痛患者循环EPCs及SDF-1琢与CCC 形成有关,VEGF可能参与该过程。