A new model of human aortic endothelial cells in vitro

Vascular endothelial cells play an important role in coagulation regulation of vascular tone and in a variety of synthetic and metabolic functions. Endothelial cells also have a pivotal role in immunological diseases atherogenesis and tumor angiogenesis. Endothelial cells are often used as system to study the pathophysiology of late complications in diabetes mellitus atherosclerotic damages and leukocyte adhesion in inflammatory diseases. Most of the studies have been performed on primary arterial and venous endothelial cell cultures with problems such as availability of autoptic material and reproducibility of cell cultures. We have isolated and characterized a novel system of proliferating long-term cultures of human aortic endothelial cells that maintain their differentiated characteristics for many generations in vitro. They produce antithrombotic and thrombotic factors such as t-PA and PAI-1 and respond to TNFalpha, an important factor correlated with the inflammatory process by modifying growth characteristics by producing cytokines such as GM-CSF by expressing ICAM-1 on the surface and by producing large amounts of nitric oxide and endothelin. This new system may be very useful to understand and study the molecular mechanisms involved in many vascular alteration pathologies and in the aging process.     

Features and incidence of thromboembolic disease: A comparative study between high and low altitude dwellers in Saudi Arabia

To estimate and compare the incidence of thromboembolic disease among patients who are clinically suspected for VTE among high and low altitude dwellers in Saudi Arabia. A prospective study conducted over two years (2011–2013) conducted in two different geographical areas in Saudi Arabia; Abha City and Riyadh City. Patients clinically suspected with deep vein thrombosis and pulmonary embolism was recruited to the study. A detailed social, medical and laboratory investigations were taken from all patients including lifestyle, occupation and smoking. A total of 234 patients participated in the study. There were 146 (62.4%) females and 88 (37.6%) males. Mean age was 51.7 years. A 56.8% incidence of DVT was seen among high altitude dwellers compared to 13.0% among low altitude dwellers. Also, a 12.6% incidence of PE was documented among high altitude dwellers, compared to 4.1% of the low altitude dwellers. VTE was significantly more among high altitude dwellers (81.9%) compared to low altitude dwellers (21.9%). Mean WBC count was significantly higher among the high altitude dwellers (10.8 ± 9.7 vs. 8.2 ± 3.4, p = 0.043). Mean platelet count was significantly higher among the high altitude dwellers compared to the low altitude dwellers (327.4 ± 162.4 vs. 212.0 ± 158.9, p = 0.005). The likelihood of developing VTE is greater among people who resided at moderate to high altitude for prolonged periods of time. The changes in the factors for coagulation including platelet counts may not reflect the true status of hypercoagulability especially if patients have stayed longer in high altitudes because of physiological adaptation to the environment.     

Correlation of thrombosis growth rate to pathological wall shear rate during platelet accumulation

Local hemodynamics may strongly influence atherothrombosis, which can lead to acute myocardial infarction and stroke. The relationship between hemodynamics and thrombosis during platelet accumulation was studied through an in vitro flow system consisting of a stenosis. Specifically, wall shear rates (WSR) ranging from 0 to 100,000 s^?1 were ascertained through computations and compared with thrombus growth rates found by image analysis for over 5,000 individual observation points per experiment. A positive correlation (P < 0.0001) was found between thrombus accumulation rates and WSR up to 6,000 s^?1, with a decrease in growth rates at WSR >6,000 s^?1 (P < 0.0001). Furthermore, growth rates at pathological shear rates were found to be two to four times greater than for physiological arterial shear rates below 400 s^?1. Platelets did not accumulate for the first minute of perfusion. The initial lag time, before discernible thrombus growth could be found, diminished with shear (P < 0.0001). These studies show the quantitative increase in thrombus growth rates with very high shear rates in stenoses onto a collagen substrate. Biotechnol. Bioeng. 2012; 109: 2642–2650. © 2012 Wiley Periodicals, Inc.     

Heparanase is a predictive marker for high thrombus burden in patients with ST-segment elevation myocardial infarction

Objective: Heparanase (HPA) is an endo-β-D-glucuronidase capable of degrading heparin sulphate (HS) and heparin side chains. HPA plays a role in tumour growth, angiogenesis, cell invasion and in activation of the coagulation system. We aimed to investigate the relationship between HPA and thrombus burden (TB) in patients with ST-Segment Elevation Myocardial Infarction (STEMI).

Methods: This prospective study enrolled 187 patients with STEMI who were treated with primary percutaneous coronary intervention (pPCI). Blood samples were taken to determine serum HPA levels prior to coronary angiography and heparin administration. Serum HPA analysis was performed with a commercially available Human Elisa kit.

Results: Patients were divided into two groups: high TB (n:58) and low TB (n:129) group. Serum HPA levels were significantly higher in patients with high TB than low TB [250.1 (188.5–338.1) vs. 173.6 (134.3–219.8) pg/mL] (p?<?0.001). Serum HPA levels were higher in patients with no-reflow phenomenon compared with others [(409.3 (375.6–512.5) pg/mL vs. 186.2 (144.2–247.4) pg/mL, p?<?0.001]. In multiple logistic regression analysis HPA was a predictor of high TB.

Conclusion: Elevated HPA level in patients with STEMI is related to high TB. Furthermore, increased HPA level may be associated with thrombotic complications such as no-reflow phenomenon in patients with STEMI.     

Haemolysis as a first sign of thromboembolic event and acute pump thrombosis in patients with the continuous-flow left ventricular assist device HeartMate II

Background

Despite advances in pump technology, thromboembolic events/acute pump thrombosis remain potentially life-threatening complications in patients with continuous-flow left ventricular assist devices (CF-LVAD). We sought to determine early signs of thromboembolic event/pump thrombosis in patients with CF-LVAD, which could lead to earlier intervention.

Methods

We analysed all HeartMate II recipients (n = 40) in our centre between December 2006 and July 2013. Thromboembolic event/pump thrombosis was defined as a transient ischaemic attack (TIA), ischaemic cerebrovascular accident (CVA), or pump thrombosis.

Results

During median LVAD support of 336 days [IQR: 182–808], 8 (20 %) patients developed a thromboembolic event/pump thrombosis (six TIA/CVA, two pump thromboses). At the time of the thromboembolic event/pump thrombosis, significantly higher pump power was seen compared with the no-thrombosis group (8.2 ± 3.0 vs. 6.4 ± 1.4 W, p = 0.02), as well as a trend towards a lower pulse index (4.1 ± 1.5 vs. 5.0 ± 1.0, p = 0.05) and a trend towards higher pump flow (5.7 ± 1.0 vs. 4.9 ± 1.9 L m, p = 0.06).The thrombosis group had a more than fourfold higher lactate dehydrogenase (LDH) median 1548 [IQR: 754–2379] vs. 363 [IQR: 325–443] U/L, p = 0.0001). Bacterial (n = 4) or viral (n = 1) infection was present in 5 out of 8 patients. LDH > 735 U/L predicted thromboembolic events/pump thrombosis with a positive predictive value of 88 %.

Conclusions

In patients with a CF-LVAD (HeartMate II), thromboembolic events and/or pump thrombosis are associated with symptoms and signs of acute haemolysis as manifested by a high LDH, elevated pump power and decreased pulse index, especially in the context of an infection.     

Thematic Review Series: High Density Lipoprotein Structure,Function, and Metabolism: Cardioprotective functions of HDLs

Multiple human population studies have established the concentration of high density lipoprotein (HDL) cholesterol as an independent, inverse predictor of the risk of having a cardiovascular event. Furthermore, HDLs have several well-documented functions with the potential to protect against cardiovascular disease. These include an ability to promote the efflux of cholesterol from macrophages in the artery wall, inhibit the oxidative modification of low density lipoproteins (LDLs), inhibit vascular inflammation, inhibit thrombosis, promote endothelial repair, promote angiogenesis, enhance endothelial function, improve diabetic control, and inhibit hematopoietic stem cell proliferation. There are undoubtedly other beneficial functions of HDLs yet to be identified. The HDL fraction in human plasma is heterogeneous, consisting of several subpopulations of particles of varying size, density, and composition. The functions of the different HDL subpopulations remain largely unknown. Given that therapies that increase the concentration of HDL cholesterol have varying effects on the levels of specific HDL subpopulations, it is of great importance to understand how distribution of different HDL subpopulations contribute to the potentially cardioprotective functions of this lipoprotein fraction. This review summarizes current understanding of the relationship of HDL subpopulations to their cardioprotective properties and highlights the gaps in current knowledge regarding this important aspect of HDL biology.     

不同方案治疗直径小于10cm肝细胞癌合并门静脉癌栓患者影响生存率的观察

目的：探讨两种不同方案治疗直径小于10cm肝细胞癌合并门静脉癌栓患者影响生存率。方法：将我院100例直径小于10cm肝细胞癌合并门静脉癌栓患者按照抽签法随机地均分为A、B两组,A组行单纯肝动脉插管化疗栓撒（TACE）治疗,B组肝癌手术切除联合癌栓切除＋TACE术,比较两组患者治疗前后DLIA蛋白与VEGF蛋白阳性表达率、五年生存率以及影响患者生存率的因素。结果：（1）A组治疗前后DLL4蛋白与VEGF蛋白阳性表达率差异无统计学意义（P〉0．05）,B组治疗前后上述蛋白阳性表达率差异具有统计学意义（P〈0．05,P〈0．01）;（2）根据Kaplan—Meir计算方法,B组五年生存率均明显大于A组（P〈0．001）;（3）经Pearson单因素与COX多因素分析,影响患者预后的危险独立因素为肿瘤大小与手术方式。结论：综合治疗方案用于治疗直径小于10cm肝细胞癌合并门静脉癌栓患者之中,疗效显著,患者五年生存率明显提高。     

下肢深静脉血栓形成的危险因素及导管接触性溶栓的临床疗效研究

目的:分析下肢深静脉血栓形成(DVT)的危险因素,并探讨导管接触性溶栓治疗下肢DVT的临床疗效。方法:选取2015年12月～2018年12月间在北京积水潭医院治疗的126例下肢DVT患者作为病例组,另外选取同期在我院健康体检的志愿者60例作为对照组,采用多因素Logistic回归分析下肢DVT的危险因素。将病例组按随机数表法分为系统溶栓组(采用系统性溶栓治疗)和导管溶栓组(采用导管接触性溶栓治疗)两个亚组,各63例。评价两组疗效,观察两组患者治疗前及治疗1个月后的双下肢周径差和静脉通畅度评分,记录并比较两组患者治疗时间、住院时间、尿激酶用量以及不良反应发生情况。结果:病例组与对照组年龄、体质量指数(BMI)、红细胞计数(RBC)、手术外伤史比较,差异有统计学意义(P0.05)。多因素Logistic回归分析结果显示,年龄、BMI、RBC、手术外伤史均是下肢DVT的独立危险因素(P0.05)。导管溶栓组痊愈率为57.14%(36/63),高于系统溶栓组的33.33%(21/63)(P0.05);治疗1个月后,两组双侧大腿周径差、双侧小腿周径差以及静脉通畅度评分均明显减小,且导管溶栓组上述指标均明显小于系统溶栓组(P0.05)。导管溶栓组治疗时间和尿激酶用量明显少于系统溶栓组,但住院时间明显长于系统溶栓组(P0.05)。两组患者不良反应发生率比较差异无统计学意义(P0.05)。结论:年龄、BMI、RBC、手术外伤史均是下肢DVT的独立危险因素,导管接触性溶栓治疗下肢DVT的疗效显著,具有较好的安全性。     

神经肌肉电刺激联合间歇性充气加压预防颅脑外伤患者下肢深静脉血栓的临床研究

摘要 目的：探讨神经肌肉电刺激（NMES）联合间歇性充气加压预防颅脑外伤患者下肢深静脉血栓（LEDVT）的临床疗效,为预防LEDVT干预措施的选择提供依据。方法：将2020年11月至2021年8月于安徽中医药大学附属六安医院就诊的72例颅脑外伤患者纳入研究对象,随机数字法分为对照组和观察组,各组36例。对照组给予常规措施+间歇性充气加压干预,观察组在对照组基础上联合NMES干预。收集患者资料,比较两组LEDVT情况、卧床时间、住院时间、干预前后凝血功能指标[凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、D-二聚体（D-D）及纤维蛋白原（FIB）]水平、腘静脉、股总静脉血液流速、视觉疼痛模拟量表（VAS）评分,日常生活能力量表（ADL）评分。结果：观察组LEDVT发生率5.56%（2/36）低于对照组25.00%（9/36）,卧床时间、住院时间短于对照组（P＜0.05）;两组干预后凝血功能指标PT、APTT、D-D、FIB水平较干预前显著改善,且观察组较对照组改善更为显著（P＜0.05）;两组干预后腘静脉、股总静脉血液流速、ADL评分较干预前升高,VAS评分较干预前降低,且观察组腘静脉、股总静脉血液流速、ADL评分高于对照组,VAS评分低于对照组（P＜0.05）。结论：NMES联合间歇性充气加压干预能缩短颅脑外伤患者卧床时间和住院时间,改善患者凝血功能和血液循环,减少LEDVT的发生,且有助于减轻患者疼痛,提高患者生活能力。     

钙蛋白酶与心血管疾病的关系

钙蛋白酶(calpain)是一种依赖Ca2+激活的蛋白水解酶,属于半胱氨酸蛋白水解酶超家族成员。钙蛋白酶广泛分布于心血管系统,可被Ca2+激活,产生多种生物学效应,如降解心肌收缩蛋白、促进细胞凋亡、参与心血管重构等。近年,钙蛋白酶与心肌缺血再灌注损伤、血栓、房颤、动脉粥样硬化等心血管疾病的关系正受到越来越多的关注。