Detailed characterization of the endocannabinoid system in human macrophages and foam cells,and anti-inflammatory role of type-2 cannabinoid receptor

Objective

Cannabinoid receptors are activated in murine macrophages upon exposure to oxidized low-density lipoproteins (oxLDL), and type-1 cannabinoid receptor (CB₁R) is considered as a risk factor in atherosclerosis, because it promotes cholesterol accumulation and release of inflammatory mediators. Conversely, accumulated evidence suggests a protective role for type-2 cannabinoid receptor (CB₂R). Here, we sought to ascertain whether different elements of the endocannabinoid system (ECS) were activated in human lipid-laden macrophages, and whether CB₂R played any role in atherogenesis and inflammation of these cells.

Methods and results

Human macrophages were exposed to oxLDL in order to obtain lipid-laden foam cells. Liquid chromatography/mass spectrometry (LC/MS) was used to measure the production of the endocannabinoids in both macrophages and foam cells, and radiometric assays were performed to measure cannabinoid receptor binding and activity of endocannabinoid metabolizing enzymes. OxLDL accumulation was investigated by confocal imaging, and cytokine production and release were measured by means of flow cytometry and ELISA. The results showed that human macrophages possess a fully functional ECS, which was modulated by oxLDL. Selective CB₂R activation reduced cellular oxLDL accumulation, which was associated with decreased expression of CD36 scavenger receptor, and decreased production of TNFα, IL-12 and IL-10. These anti-atherogenic and anti-inflammatory effects were reverted by the selective CB₂R antagonist SR144528.

Conclusions

A fully active ECS is present in human macrophages and macrophage-derived foam cells. Selective activation of CB₂R reduces CD36-dependent oxLDL accumulation and modulates production of inflammatory cytokines, thus representing a potential therapeutic strategy to combat atherosclerosis.     

Cellular endotoxin desensitization in patients with severe chronic heart failure

BACKGROUND: Increased levels of bacterial lipopolysaccharide (LPS) have been demonstrated in chronic heart failure (CHF). LPS can induce cellular desensitization, with specific down-regulation of LPS-mediated cellular tumor necrosis factor (TNF-alpha) production which does not affect other cytokine parameters. It is not known if LPS desensitization occurs in CHF. METHODS AND RESULTS: Mononuclear cells from 24 CHF patients (mean age 70+/-2 years, age range 58 to 78 years, NYHA class 3.0+/-0.2) and 11 healthy controls (mean age 53+/-3 years, age range 39 to 75 years) were separated from venous blood and cultured for 24 h with LPS (E. coli, 0-10 ng/mL). Culture supernatants were tested for TNF-alpha and interleukin-1 receptor antagonist (IL-1RA). Patients were subgrouped into mild (n=10), moderate (n=5), and severe (n=9) CHF. Independently of age, mononuclear cells from patients with severe heart failure produced less TNF-alpha than controls (p<0.05) and patients with mild (p<0.001) or moderate CHF (p<0.05). IL-1RA release was higher for CHF patients as a group, compared with controls (p<0.05). There was no significant difference in IL-1RA release between CHF patient subgroups. CONCLUSIONS: Mononuclear cells from patients with severe heart failure produce significantly less TNF-alpha than healthy controls or patients with mild to moderate disease. Production of IL-1RA is not affected. This resembles a picture indicative of LPS desensitization occurring in patients with severe CHF.     

Combination therapy with carvedilol and amiodarone in patients with severe heart failure

BACKGROUND: Carvedilol and at least in some studies, amiodarone have been shown to improve symptoms and prognosis of patients with heart failure. There are no reports on the outcome of combined treatment with both drugs on top of angiotensin-converting enzyme inhibitors (ACEI), diuretics and digitalis. METHODS AND RESULTS: In 109 patients with severe heart failure submitted for heart transplantation at one single center between the years 1996 and 1998 [left ventricular ejection fraction (LVEF) 24.6+/-11%, 85% males, 52% idiopathic dilated cardiomyopathy (DCM), mean observation time 1. 9+/-0.4 years] a therapy with low-dose amiodarone (1000 mg/week) plus titrated doses of carvedilol (target 50 mg/day) was instituted. In addition, patients received a prophylactic dual chamber pacemaker (PM) in order to protect from bradycardia and for continuous holter monitoring. The devices were programmed in back-up mode with a basal rate of 40 i.p.m. with a hysteresis of 25%. Significantly, more patients were in sinus rhythm after 1 year than at study entry (85% vs. 63%, P<0.01). In 47 patients, under therapy over at least 1 year, the resting heart rate fell from 90+/-19 to 59+/-5 b.p.m. (P<0.001). Ventricular premature contractions in 24-h holter ECGs were suppressed from 1.0+/-3 to 0.1+/-0.3%/24 h (P167 b.p.m. detected by the pacemaker (1.2+/-2.8 episodes/patient/3 months vs. 0.3+/-0.8 episodes/patient/3 months after 1 year (P<0.01). The LVEF increased from 26+/-10 to 39+/-13% (P<0.001). NYHA class improved from 3. 17+/-0.3 to 1.8+/-0.6 (P<0.001) as well as right heart catheterization data. From the total cohort, seven patients (6%) developed symptomatic documented bradycardic rhythm disturbances requiring reprogramming of their pacemakers to DDD(R)/VVI(R) mode with higher basic rates. Two of these patients developed AV block, four sinu-atrial blocks or sinus bradycardia and one patient had bradycardic atrial fibrillation. During the observation period five patients died (3 sudden, 1 due to heart failure and 1 due to mesenteric infarction). Two patients had undergone heart transplants. The 1-year survival rate (Kaplan-Meier) without transplantation was 89%. Compared to historic control patients with amiodarone only (n=154) or without either agent (n=283) this rate was 64 and 57% (P<0.01). CONCLUSIONS: Heart failure patients benefit from a combined therapy with carvedilol and amiodarone resulting in a markedly improved NYHA stage, an increase in LV ejection fraction, a stabilization of sinus rhythm, a significant reduction in heart rate, a delay of electrical signal conduction and a suppression of ventricular ectopies. Approximately 6% of patients under such a regime became pacemaker-dependent in the first year. Compared to historic controls prognosis was better and the need for heart transplantation was lower. The exact role of either agent in combination or alone should be clarified in larger randomized studies.     

血管紧张素Ⅱ1型受体基因多态性与心力衰竭预后的相关性研究

目的评价血管紧张素Ⅱ1型受体(AngiotensinⅡtype 1 receptor,AT1R)基因1166位点A/C基因多态性对心力衰竭预后的影响。方法432例患者来源于美国匹兹堡大学医疗中心的心血管事件基因危险性评价研究组,均有收缩功能障碍性心力衰竭〔射血分数(EF)<0.45〕。入选时间为1996年4月至2001年1月,前瞻性随访患者(26.43±18.19)月,随访终点是死亡或心脏移植。用聚合酶链式反应(PCR)方法鉴定AT1R基因A1166C位点基因型,分析AT1R A1166C基因多态性对心力衰竭患者生存率的影响。结果AT1R纯合子CC型8.6%,纯合子AA型50.0%,杂合子AC型41.4%。三组基因型在年龄、性别、种族、病因、血压和治疗方面无显著性差异,而在NYHA心功能分级的比例有显著性差异,AT1R C等位基因与较低心功能分级密切相关(P=0.04),但随访三组基因型的三年生存率并无显著性差异。结论在本组收缩功能障碍性心力衰竭患者中,AT1R C等位基因仅与较低心功能分级密切相关,并不影响未行心脏移植心力衰竭患者的预后。     

双心室起搏在严重心力衰竭病人中的应用

目的：探讨双心室心脏起搏在技术上的可行性及其在严重心力衰竭中的应用价值。方法：４例原发性扩张型心肌病,心功能Ⅲ或Ⅳ级,合并左束支传导阻滞,ＱＲＳ时间≥２０ｍｓ。经锁骨下静脉将左心室外膜起搏电极置于心脏后侧支静脉,按常规方法安置右心房和右心室电极。起搏器程控为ＤＤＤ工作方式,ＡＶ间期设置为１００ｍｓ。在１２个月随访中,观察临床、心电图、运动试验（６ｍｉｎ步行距离）和超声心动图指标的变化以评价疗效。结果：（１）４例均成功安置双心室心脏起搏器,术后心力衰竭症状明显缓解,并于手术后９～２０ｄ出院。出院前停用所有静脉用药,包括利尿剂、强心剂和扩血管药;（２）随访：４例心功能均改善一级,６ｍｉｎ步行距离增加７６～２８４ｍ。超声心动图显示：左心室和左心房前后径分别减小３～７ｍｍ和２～７ｍｍ,左心室射血分数增加４％～７％。结论     

内皮素受体基因在心力衰竭患者外周血的表达及意义

目的 :研究充血性心力衰竭 (心衰 )患者血浆内皮素 (ET)水平和ET受体基因在其外周血单个核细胞表达情况。方法 :在 36例心衰 (心衰组 )患者和 12例健康人 (对照组 )中分别采用放免法测定血浆ET水平、逆转录聚合酶链反应检测ET受体基因在其外周血单个核细胞的表达。结果 :心衰组血浆ET水平〔(4 .90± 1.96 )pmol L〕明显高于对照组〔(1.76± 0 .82 )pmol L〕(P <0 .0 1)。ET受体基因表达阳性率在两组差异无显著性意义(P >0 .0 5 ) ,半定量后 ,心衰组ETA受体 (0 .82± 0 .2 6 )表达水平明显高于对照组 (0 .5 9± 0 .17) (P <0 .0 1)。结论 :ET及其A受体与心衰的发生、发展有密切关系     

Safety and efficacy of adaptive servo-ventilation in patients with severe systolic heart failure

Background and purposeIt is unclear whether adaptive servo-ventilation (ASV) is safe and effective in patients with severe systolic heart failure (HF). Our aim in this study was to estimate the safety and efficacy of ASV therapy for patients with severe systolic HF.Methods and subjectsSeventy-six HF patients (age: 69 ± 12 years; 53 men), categorized as New York Heart Association (NYHA) Class II–IV, with left ventricular ejection fraction (LVEF) of <50%, received ASV therapy after optimal medical therapy to determine the safety and efficacy of ASV. Patients were divided into 2 groups based on their LVEF: group L (LVEF < 30%; n = 42) and group H (LVEF ≥ 30%; n = 34). After 6 months of ASV therapy, we compared the changes in LVEF, brain natriuretic peptide (BNP), and incidence of fatal cardiovascular events between the groups.ResultsThe groups differed significantly with respect to beta-blocker treatment before ASV therapy (p < 0.0001). After 6 months of ASV therapy, LVEF and BNP levels had improved in both groups. In group L, LVEF had improved from 24.1 ± 5.6% to 35.2 ± 10.6% (p < 0.0001) and BNP from 591 (273–993) pg/ml to 142 (39–325) pg/ml (p = 0.002). Moreover, 1-year follow-up data showed a tendency toward improvement of NYHA classification in group L (group L: 50%; group H: 29%; p = 0.07), and showed no significant difference with regard to fatal cardiovascular events between the 2 groups (group L: 11.9%; group H: 5.9%; p = 0.36).ConclusionsOur study demonstrated that ASV therapy is safe and effective for use in very severe systolic HF patients as well as in relatively mild systolic HF patients.     

血浆细胞因子水平与老年慢性心力衰竭患者多器官功能衰竭的关系

目的　探讨老年慢性心力衰竭 (CHF)时多器官功能衰竭 (MOF)的发生与血浆细胞因子的关系。方法　 6 2例老年CHF者 ,男 4 4例 ,女 18例 ,平均年龄 (70± 13)岁。根据是否合并MOF分为单纯CHF组和CHF MOF组 ,各 31例 ;再根据治疗后是否存活分为存活及死亡两个亚组。另设正常对照组 31例。分别于入院时和治疗后测定左室射血分数 (LVEF) ,血浆肿瘤坏死因子α(TNFα)、白介素 1β(IL 1β)、可溶性细胞间粘附分子 1(sICAM 1)、心钠素 (ANP)水平。结果　血浆中TNFα ,IL 1β ,sICAM 1水平在存活与死亡之间比较 ,MOF组较CHF组明显升高 ;而组内比较 ,死亡者又较存活者明显增加。CHF组与MOF组在同是存活或死亡之间比较 ,LVEF和ANP无明显差异 ,但两组内存活和死亡者之间比较 ,在治疗后则有明显差异 ;两组治疗后与治疗前比较均有明显差异 ,存活者改善而死亡者恶化。结论　细胞因子TNFα,IL 1β ,ICAM 1的血浆水平增加与MOF的发生发展密切相关 ,通过检测血浆中上述细胞因子的水平 ,可作为判断有无MOF及其严重程度的指标。     

Low urinary 6-sulfatoxymelatonin levels in patients with severe congestive heart failure

Objective: To assess urinary 6-sulfatoxymelatonin excretion in patients admitted to the hospital because of congestive heart failure (CHF). Methods: Urinary 6-sulfatoxymelatonin was measured by a specific radioimmunoassay in 33 hospitalized patients with CHF and in 146 healthy ambulatory volunteers. Individuals with hepatic or renal failure were excluded from the sample. Data were analyzed by the Mann-Whitney test and regression analysis. Results: 6-Sulfatoxymelatonin levels were significantly lower in CHF patients than controls (median 2.6 vs 6.02 μg, p<0.0001). This decrease was observed regardless of β-adrenergic blocker or benzodiazepine medication. A significant decrease in 6-sulfatoxymelatonin excretion occurred with age. There were no significant differences in urinary 6-sulfatoxymelatonin levels between chronic and acute CHF patients. Conclusions: The results suggest that circulating melatonin levels are low in patients with CHF. Such a decrease may precede aggravation of heart failure.     

老年重症心力衰竭急诊内科治疗的临床研究

目的研究老年重症心力衰竭急诊内科的临床治疗效果。方法选取我院2013年1月至2014年1月间收治的重症心力衰竭急诊内科病患80例,将病患随机地划分成对照组和观察组,对照组采用常规疗法,观察组在常规疗法的基础上,选用美托洛尔合并厄贝沙坦氢氯噻嗪的方式完成治疗,观察并对比两组的临床疗效,对临床结果开展回顾性分析。结果对照组的疗效,3例为优,占7.5%,26例为良,占65.0%,11例为差,占27.5%,本组治疗的总有效率为72.5%;观察组的疗效,8例为优,占20.0%,31例为良,占77.5%,1例为差,占2.5%,本组治疗的总有效率为97.5%。两组病患在疗效优良率方面有显著性差异,P0.05表明具备统计学意义。结论运用美托洛尔合并厄贝沙坦氢氯噻嗪治疗老年重症心力衰竭的临床效果显著,是一类可靠、理想的疗法,值得临床推广和应用。     

Soluble TNF-alpha and interleukin-6 receptors in the urine of heart failure patients. Their clinical value and relationship with plasma levels

BACKGROUND: Proinflammatory cytokines are important mediators in heart failure (HF). Recently, urinary levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) have been determined. AIMS: The purpose of this study was to measure the urinary levels of TNF-alpha and IL-6 receptors, sTNF-RI, sTNF-RII, sIL-6R, and the relationship with plasma levels and NYHA classes in HF. METHODS: Plasma and urine were collected from 114 HF patients and sTNF-RI, sTNF-RII and sIL-6R (ng/ml) were analyzed. RESULTS: For the whole population, plasma levels of sTNF-RI were 2.1+/-0.1, of sTNF-RII were 5.0+/-0.3 and of sIL-6R were 49.8+/-2.5. Urinary levels were: sTNF-RI, 2.8+/-0.5, r=0.5, p<0.001; sTNF-RII, 12.6+/-2.1, r=0.4, p<0.001; and sIL-6R, 4.2+/-0.4, NS. In NYHA III subjects, we found sTNF-RI, r=0.6, p<0.01, sTNF-RII, r=0.5, p<0.05, and sILR-6, r=0.5, p<0.05. Both plasma TNF receptors and urinary levels of sTNF-RII were higher in patients in a more severe NYHA class (p<0.05). CONCLUSIONS: Urine is a good environment to study sTNF-RI and sTNF-RII, and this fact has diagnostic and prognostic implications. Plasma and urinary levels of TNF receptors showed a fair correlation, which was increased in higher NYHA classes. Plasma and urinary levels of sIL6R showed a good correlation in NYHA III. The TNF receptor levels in urine increased in patients with more severe HF.     

充血性心力衰竭患者窦性心率震荡现象及其临床意义

目的观察心率震荡(HRT)现象在慢性充血性心力衰竭(CHF)患者中的变化,并探讨其临床意义。方法选择66例CHF患者和30例室性期前收缩者(对照组)。其中CHF患者按纽约心功能分级(NYHA)分为轻度CHF组(NYHAⅡ级,29例)和重度CHF组(NYHAⅢ～Ⅳ级,37例);又根据预后不同分为死亡组(11例)和生存组(55例)。所有研究对象经超声心动图测量左心室射血分数(LVEF)和左心室舒张末期内径(LVEDD),并行动态心电图(Holter)检查,获取震荡初始(TO)和震荡斜率(TS)。结果 CHF患者HRT现象明显减弱,CHF组TO和LVEDD明显大于对照组[1.65%±1.49%比-1.02%±0.76%;(59.85±4.46)mm比(47.64±4.96)mm,均为P<0.01],TS和LVEF明显小于对照组[(4.13±2.07)ms/RR比(7.86±3.02)ms/RR;53.34%±11.00%比69.46%±12.75%,均为P<0.01]。重度CHF组TO高于轻度CHF组,但差异无统计学意义。重度CHF组Ts和LVEF则明显低于轻度CHF组[(3.22±1.52)ms/RR比(5.28±2.12)ms/RR;46.34%±6.88%比62.20%±8.59%,均为P<0.01],LVEDD明显大于轻度CHF组[(59.53±4.91)mm比(55.27±3.91)mm,P<0.01]。死亡组TS和LVEF明显低于生存组[(1.92±0.79)ms/RR比(4.34±1.97)ms/RR,44.27%±7.50%比55.09%±10.75%,均为P<0.01],LVEDD和TO明显大于生存组[(58.45±5.11)mm比(55.35±4.19)mm,2.75%±1.75%比1.43%±1.35%,均为P<0.05]。HRT 0级:生存组患者多于死亡组[8例(14.5%)比0(0),P>0.05],HRT 1级:生存组患者明显多于死亡组[39例(70.9%)比3例(27.3%),P<0.05],HRT 2级:生存组患者明显少于死亡组[8例(14.5%)比8例(72.7%),P<0.01]。死亡与TO、HRT 2级和LVEDD呈正相关(均为P<0.05),与TS和LVEF呈负相关(P<0.01)。结论重度CHF患者心率震荡现象明显减弱,HRT可作为CHF患者危险性评估的指标。     

Nutrient intake and serum cytokine pattern in elderly people with heart failure

BACKGROUND: Heart failure (HF) is frequently complicated by malnutrition. We estimated nutrient intake in HF patients and evaluated the correlation between serum cytokines and dietary pattern. METHODS: We studied 124 elderly (>or=60 years) patients with severe HF (N=62) or without HF (controls, N=62), matched for age and sex. Nutritional data were obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. We compared the intake of macro- and micronutrients in the two groups; in the HF group nutritional intake was correlated with serum cytokines. RESULTS: HF patients had a lower energy intake (26.8 Kcal/Kg of ideal weight vs. 37.3 Kcal /Kg ideal weight in controls, P<0.001) due to a lower intake of all macronutrients. The energy intake was lower than the recommended (30 Kcal/Kg of ideal body weight) in 72% of HF and 34% of the controls. The intake of several minerals and vitamins was inferior to the recommended dietary allowance (RDA) in most participants. Those HF patients with a caloric intake below the median (22.6 Kcal/Kg ideal weight) did not differ substantially from those with higher caloric intake with regard to age, functional characteristics, and lean body mass as expressed by the mid-arm muscle circumference, however, they had a higher concentration of IL4 (61.5 pg/ml vs. 37.7 pg/ml, P=0.075) and of IL10 (6.32 pg/ml vs. 2.06 pg/ml, P=0.046). CONCLUSIONS: Nutritional intake is frequently inadequate in patients with severe HF. Our results suggest that some interleukins might affect caloric intake in patients with HF.     

卡维地洛治疗充血性心力衰竭的临床研究

目的:探讨卡维地洛对充血性心力衰竭(CHF)患者心功能的影响。方法:45例CHF患者被随机分成2组.对照组(B组)用利尿剂、强心甙、硝酸酯类等药进行治疗,治疗组(A组)在B组治疗基础上加用卡维地洛,起始剂量3.125mg,2次/d,每2周加量1倍,至最大剂量25mg,2次/d。结果:治疗16周后,两组的心功能分级均有明显改善.与对照组比较,治疗组LVEF增加更加显著(P<0.05)。结论:卡维地洛对CHF有较好的疗效。     

卡维地洛对心功能不全患者神经激素系统的影响

目的探讨卡维地洛对慢性心功能不全患者神经激素及肾上腺素受体β1、β2、α1自身抗体的影响。方法60例慢性心功能不全患者随机分为卡维地洛组（36例）和常规治疗组（24例）。常规治疗组应用血管紧张素转换酶抑制剂、利尿剂和洋地黄制剂。卡维地洛组在此基础上加用卡维地洛。随访半年,超声心动图测定心功能参数,检测血浆去甲肾上腺素（NE）、肾素（PRA）、血管紧张素II（AngII）、醛固酮（ALD）、及对抗心脏β1、β2、α1自身抗体。结果治疗后,卡维地洛组左室舒张末内径和收缩末内径分别为（57±6）mm和（43±6）mm显著低于常规治疗组的（64±5）mm和（52±5）mm（均P<0.01）;左室射血分数为（51±8）%,显著高于常规治疗组的（42±6）%（P<0.01）。治疗后卡维地洛组血浆NE、PRA、AngII、ALD、3种抗体滴度均显著降低（均P<0.01）,且卡维地洛组血浆NE、PRA、AngII、ALD水平、3种抗体滴度也显著低于常规治疗组,差异有统计学意义（P<0.05）。结论卡维地洛通过阻断神经激素激活及降低心衰患者心脏自身β1、β2、α1受体抗体水平而改善心功能。     

心区交感神经阻滞对扩张型心肌病严重心力衰竭疗效观察

目的观察心区交感神经阻滞对扩张型心肌病严重心力衰竭患者心脏功能的影响。方法随机选取扩张型心肌病严重心力衰竭患者39名,分为对照组和治疗组。对照组给予常规治疗,治疗组在常规治疗的同时进行心区交感神经阻滞(胸1-5),0.5%利多卡因每2小时经胸段硬膜外导管推注1次(除夜间睡眠外)。所有患者于治疗前和治疗后1个月进行心脏彩超检查,测量左心室射血分数(EF),短轴缩短率(FS),二尖瓣关闭时间和左心室射血时间,计算心肌功能指数(MPI),比较治疗前后心功能分级和上述指标的变化。结果治疗后对照组与治疗组的心功能分级均明显改善,但治疗组心功能分级好于对照组(2.13±0.63,2.88±0.62,P< 0.01);治疗后治疗组心功能分级差值明显大于对照组(1.74±0.54,1.06±0.68,P< 0.05);与治疗前比较,治疗后治疗组左心室射血时间、EF和FS均显著增加,MPI明显降低(0.71±0.23,0.55±0.35,P< 0.05),而对照组上述指标均无显著变化。结论心区交感神经阻滞能显著改善扩张型心肌病严重心力衰竭患者,左心室功能;对心功能分级改善的程度优于常规治疗。     

AXL receptor tyrosine kinase is increased in patients with heart failure

Background

AXL is a membrane receptor tyrosine kinase highly expressed in the heart and has a conspicuous role in cardiovascular physiology. The role of AXL in heart failure (HF) has not been previously addressed.

Methods and results

AXL protein was enhanced 6-fold in myocardial biopsies of end-stage HF patients undergoing heart transplantation compared to controls from heart donors (P < 0.0001). Next, we performed a transversal study of patients with chronic HF (n = 192) and a group of controls with no HF (n = 67). sAXL and BNP circulating levels were quantified and clinical and demographic data were collected.sAXL levels in serum were higher in HF (86.3 ± 2.0 ng/mL) than in controls (67.8 ± 2.0 ng/mL; P < 0.0001). Also, sAXL correlated with several parameters associated with worse prognosis in HF. Linear regression analysis indicated that serum creatinine, systolic blood pressure and atrial fibrillation, but not BNP levels, were predictive of sAXL levels. Cox regression analysis indicated that high sAXL values at enrollment time were related to the major HF events (all-cause mortality, heart transplantation and HF hospitalizations) at one year follow-up (P < 0.001), adding predictive value to high BNP levels.

Conclusions

Myocardial expression and serum concentration of AXL is elevated in HF patients compared to controls. Furthermore, peripheral sAXL correlates with parameters associated with the progression of HF and with HF events at short term follow-up. All together these results suggest that sAXL could belong to a new molecular pathway involved in myocardial damage in HF, independent from BNP.     

心力衰竭患者血浆中环状RNA表达谱差异分析

目的探讨心力衰竭患者血浆中环状RNA(circRNA)表达谱的变化。方法应用高通量芯片技术分析3例心力衰竭患者和3例对照血浆中circRNA的表达谱,筛选出差异性表达的circRNA,并进行聚类分析和生物信息学预测。结果芯片检测结果显示血浆circRNA表达谱在心力衰竭患者和疾病对照之间存在差异。其中在心力衰竭患者血浆中高表达的有109种,低表达的有178种(变化>1.2倍且P<0.05)。应用TargetScan和miRanda软件预测每种差异circRNA结合匹配值较高的5个微小RNA(miRNA),其中包括miR-194、miR-204、miR-211,均为在心力衰竭发生发展中起着重要调控作用的miRNA。结论心力衰竭患者与疾病对照比较,血浆circRNA表达谱发生明显变化,这些差异表达的circRNA可能与心力衰竭的发生发展相关。     

不同血压心力衰竭患者肾素-血管紧张素-醛固酮系统的活性

目的为探讨不同血压的充血性心力衰竭(CHF)患者肾素-血管紧张素-醛固酮系统(RAAS)的活性。方法运用放免法测定收缩压(SBP)<100mmHg(1mmHg=0．133kPa)的CHF患者(LPCHF组,22例),SBP>100mmHg的CHF患者(HPCHF组,25例)及健康人(对照组,18例)血浆肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)及醛固酮(ALD)水平。结果LPCHF组及HPCHF组血浆PRA、AngⅡ和ALD均明显高于对照组(P<0．05～0．01),LPCHF组血清钠、SBP及脉压SBP显著低于对照组(P<0．05～0．01);LPCHF组血浆PRA、AngⅡ和ALD高于HPCHF组(P<0．05～0．01),LPCHF组血清钠、SBP及脉压SBP显著低于HPCHF组(P<0．05～0．01);CHF患者脉压SBP与血浆AngⅡ及ALD呈显著负相关(r=－0．501,P<0．01,r=－0．439,P<0．01)。结论CHF患者体内RAAS活性增高,且SBP<100mmHg者较SBP>100mmHg更高。