Comparative Gene Expression Analysis of Mouse and Human Cardiac Maturation

Understanding how human cardiomyocytes mature is crucial to realizing stem cell-based heart regeneration, modeling adult heart diseases, and facilitating drug discovery. However, it is not feasible to analyze human samples for maturation due to inaccessibility to samples while cardiomy-ocytes mature during fetal development and childhood, as well as difficulty in avoiding variations among individuals. Using model animals such as mice can be a useful strategy;nonetheless, it is not well-understood whether and to what degree gene expression profiles during maturation are shared between humans and mice. Therefore, we performed a comparative gene expression analysis of mice and human samples. First, we examined two distinct mice microarray platforms for shared gene expression profiles, aiming to increase reliability of the analysis. We identified a set of genes display-ing progressive changes during maturation based on principal component analysis. Second, we demonstrated that the genes identified had a differential expression pattern between adult and ear-lier stages (e.g., fetus) common in mice and humans. Our findings provide a foundation for further genetic studies of cardiomyocyte maturation.     

The influence of right ventricular stimulation on acute response to cardiac resynchronisation therapy

Background

The contribution of right ventricular (RV) stimulation to cardiac resynchronisation therapy (CRT) remains controversial. RV stimulation might be associated with adverse haemodynamic effects, dependent on intrinsic right bundle branch conduction, presence of scar, RV function and other factors which may partly explain non-response to CRT. This study investigates to what degree RV stimulation modulates response to biventricular (BiV) stimulation in CRT candidates and which baseline factors, assessed by cardiac magnetic resonance imaging, determine this modulation.

Methods and results

Forty-one patients (24 (59 %) males, 67 ± 10 years, QRS 153 ± 22 ms, 21 (51 %) ischaemic cardiomyopathy, left ventricular (LV) ejection fraction 25 ± 7 %), who successfully underwent temporary stimulation with pacing leads in the RV apex (RV_apex) and left ventricular posterolateral (PL) wall were included. Stroke work, assessed by a conductance catheter, was used to assess acute haemodynamic response during baseline conditions and RV_apex, PL (LV) and PL+RV_apex (BiV) stimulation.Compared with baseline, stroke work improved similarly during LV and BiV stimulation (∆+ 51 ± 42 % and ∆+ 48 ± 47 %, both p < 0.001), but individual response showed substantial differences between LV and BiV stimulation. Multivariate analysis revealed that RV ejection fraction (β = 1.01, p = 0.02) was an independent predictor for stroke work response during LV stimulation, but not for BiV stimulation. Other parameters, including atrioventricular delay and scar presence and localisation, did not predict stroke work response in CRT.

Conclusion

The haemodynamic effect of addition of RV_apex stimulation to LV stimulation differs widely among patients receiving CRT. Poor RV function is associated with poor response to LV but not BiV stimulation.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-015-0770-x) contains supplementary material, which is available to authorized users.     

β-arrestin 2 attenuates cardiac dysfunction in polymicrobial sepsis through gp130 and p38

Sepsis is an exaggerated systemic inflammatory response to persistent bacteria infection with high morbidity and mortality rate clinically. β-arrestin 2 modulates cell survival and cell death in different systems. However, the effect of β-arrestin 2 on sepsis-induced cardiac dysfunction is not yet known. Here, we show that β-arrestin 2 overexpression significantly enhances animal survival following cecal ligation and puncture (CLP)-induced sepsis. Importantly, overexpression of β-arrestin 2 in mice prevents CLP-induced cardiac dysfunction. Also, β-arrestin 2 overexpression dramatically attenuates CLP-induced myocardial gp130 and p38 mitogen-activated protein kinase (MAPK) phosphorylation levels following CLP. Therefore, β-arrestin 2 prevents CLP-induced cardiac dysfunction through gp130 and p38. These results suggest that modulation of β-arrestin 2 might provide a novel therapeutic approach to prevent cardiac dysfunction in patients with sepsis.     

rh-BNP联合阿托伐他汀治疗急性心梗后心衰的临床疗效及对患者血清cTn-I、Myo、CK-MB水平的影响

目的:研究重组人脑利钠肽(rh-BNP)联合阿托伐他汀治疗急性心梗后心衰的临床效果及对患者血清心肌肌钙蛋白(cardiac troponin,cTn-I)、肌红蛋白(Myoglobin,Myo)、肌酸激酶同工酶(CK-MB)水平的影响。方法:选择我院2017年2月～2019年1月收治的72例急性心梗后心衰患者,按随机数字表法分为观察组38例,对照组34例。对照组给予阿托伐他汀治疗,观察组在对照组基础上另加rh-BNP,观察和比较两组的临床疗效,治疗前后血清cTn-I、Myo、CK-MB水平的变化及治疗后不良反应的发生情况。结果:治疗后,观察组总有效率明显高于对照组(P0.05),血清cTn-I、Myo、CK-MB水平均显著低于对照组[(0.23±0.10) vs.(0.16±0.08)、(27.54±3.86) vs.(21.62±2.54)、(70.82±9.25) vs.(61.28±8.33)](P0.05)。观察组治疗后不良反情况总发生率为7.89%,明显低于对照组(26.47%,P0.05)。结论:与单用阿托伐他汀治疗相比,静脉注射rh-BNP联合阿托伐他汀治疗急性心梗后心衰可显著提高临床疗效和安全性,有效减低血清cTn-I、Myo、CK-MB水平。     

慢性心力衰竭患者N端脑钠肽前体、脑钠肽与患者心脏超声参数及炎症因子的关系

目的:探讨慢性心力衰竭(CHF)患者N端脑钠肽前体(NT-proBNP)、脑钠肽(BNP)与患者心脏超声参数及炎症因子的关系。方法:选取2015年3月～2018年2月期间我院收治的CHF患者135例为研究组。根据纽约心脏病学协会(NYHA)心功能分级将研究组分为Ⅰ级组26例,Ⅱ级组34例,Ⅲ级组42例,IV级组33例。另选取同期于我院体检的健康志愿者30例为对照组。检测并比较对照组与研究组、不同NYHA心功能分级的血清标志物、炎症因子、心功能超声参数,采用Pearson相关性分析NT-proBNP、BNP与炎症因子、心功能超声参数的相关性。结果:研究组血清BNP、NT-proBNP、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)水平及左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)均显著高于对照组,左心室射血分数(LVEF)则低于对照组(P0.05)。BNP、NT-proBNP、IL-6、TNF-α、hs-CRP水平及LVEDD、LVESD随心功能分级的升高而升高,LVEF随心功能分级的升高而降低(P0.05)。经Pearson相关性分析显示,CHF患者BNP、NT-proBNP与IL-6、TNF-α、hs-CRP、LVEDD、LVESD呈正相关,而与LVEF呈负相关(P0.05)。结论:血清NT-proBNP、BNP与CHF患者的心脏超声参数及炎症因子密切相关,可考虑将其作为临床诊断CHF的生物学指标。     

祛痰通阳汤对慢性心衰大鼠心肌损伤的保护作用及机制

目的:观察不同剂量祛痰通阳汤对慢性心衰大鼠心肌损伤的保护作用及可能机制。方法:将90只Wistar大鼠随机均分正常组、模型组、卡托普利组、祛痰通阳汤低、中、高剂量六组。为建立慢性心力衰竭模型,除正常组外的五组大鼠均以2ml/kg给予阿霉素腹腔,一周1次,共6周。注射造模成功后次日进行灌胃给予对应的不同药物,连续给药治疗四周后,应用ELISA法测定各组大鼠血浆脑尿钠肽(Brain natriuretic peptide,BNP)水平,称重计算心脏质量指数并采用投射电镜观察心肌细胞结构,通过实时荧光定量PCR法测定检测Kelch样环氧氯丙烷相关蛋白-1 (epoxy chloropro-pane Kelch sample related protein-1,Keap1)和核因子E2相关因子2(nuclearfactor erythroid-2 related factor 2,Nrf2)mRNA的表达。结果:1.电镜结果显示:正常组肌丝排列规则,肌节结构清晰,心肌细胞线粒体清晰且形态正常;细胞核发育良好,无空泡以及集块现象。模型组肌原纤维排列紊乱,心肌细胞线粒体形态异常,排列不齐,增生明显,有空泡现象形成。卡托普利组及祛痰通阳汤高剂量组电镜肌原纤维排列基本整齐,线粒体未见明显肿胀,线粒体嵴密集,优于中药低剂量组及中剂量组。2.卡托普利组、中药高剂量组大鼠血浆BNP水平较模型组显著降低(P0.01)。3.与模型组相比,中药高剂量组和卡托普利组心脏质量指数均显著降低(P0.05)。4.卡托普利组及祛痰通阳汤高剂量组心肌组织Keap1 m RNA表达与模型组相比显著降低(P0.05);卡托普利组及祛痰通阳汤高剂量组心肌组织Nrf2 m RNA表达与模型组的相比显著提高(P0.05)。结论:高剂量祛痰通阳汤可显著减轻慢性心衰大鼠的心肌损伤,可能与抑制Keap1 m RNA的表达及增强Nrf2 m RNA表达,进而抗心肌氧化损伤有关。