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Excitation-Contraction Coupling Time is More Sensitive in Evaluating Cardiac Systolic Function

Chinese Medical Journal 2018年第15期131卷 1834-1839页

作者： Juan Gao Min Zhu Hai-Yi Yu Shi-Qiang Wang Xin-Heng Feng Ming Xu Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry of Health Key Laboratory of Molecular Cardiovascular Science Ministry of Education Beijing Key Laboratory of Cardiovascular Receptors Research Beijing 100191 China State Key Laboratory of Membrane Biology College of Life Sciences Peking University Beijing 100871 China

Background： Pressure overload-induced myocardial hypertrophy is a key step leading to heart failure. Previous cellular and animal studies demonstrated that deteriorated excitation-contraction coupling occurs as early as the compensated stage of hypertrophy before the global decrease in left ventricular ejection fraction （LVEF）. This study was to evaluate the cardiac electromechanical coupling time in evaluating cardiac systolic function in the early stage of heart failure. Methods： Twenty-six patients with Stage B heart failure （SBHF） and 31 healthy controls （CONs） were enrolled in this study. M-mode echocardiography was performed to measure LVEF. Tissue Doppler imaging （TDI） combined with electrocardiography （ECG） was used to measure cardiac electromechanical coupling time. Results： There was no significant difference in LVEF between SBHF patients and CONs （64.23 ± 8.91% vs. 64.52 ± 5.90%; P= 0.886）. However, all four electromechanical coupling time courses （Qsb： onset of Q wave on ECG to beginning of S wave on TDI, Qst： onset of Q wave on ECG to top of S wave on TDI, Rsb： top of R wave on ECG to beginning orS wave on TDI, and Rst： top of R wave on ECG to top orS wave on TDI） of SBHF patients were significantly longer than those of CONs （Qsb： 119.19 ± 35.68 ms vs. 80.30 ± 14.81 ms, P 〈 0.001 ; Qst： 165.42 ± 60.93 ms vs. 129.04 ± 16.97 ms, P = 0.006; Rsb： 82.43 ± 33.66 ms vs. 48.30 ± 15.18 ms, P 〈 0.001; and Rst： 122.37 ± 36.66 ins vs. 93.25 ± 16.72 ms, P = 0.001 ）, and the Qsb, Rsb, and Rst time showed a significantly higher sensitivity than LVEF （Rst： P =0.032; Rsb： P = 0.003; and Qsb： P = 0.004）. Conclusions： The cardiac electromechanical coupling time is more sensitive than LVEF in evaluating cardiac systolic function.

关键词： Excitation-Contraction Couplings Heart Failure Left Ventricular Dysfunction

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Composition and Functional Capacity of Gut Microbes are Associated with Arterial Stiffness:A Prospective Study

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Cardiology Discovery 2023年第2期3卷 102-111页

作者： Jing Li Yixuan Zhong Jingjing Bai Shuohua Chen Jun Cai Shouling Wu Weili Zhang Heart Center&Beijing Key Laboratory of Hypertension Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China National Clinical research Center of cardiovascular Diseases State Key Laboratory of Cardiovascular DiseaseFuWai HospitalNational Center for Cardiovascular DiseasesPeking Union Medical College&Chinese Academy of Medical SciencesBeijing 100037China Department of Cardiology Kailuan General HospitalTangshanHebei 063000China Central-China Branch of National Center for cardiovascular Diseases Henan Cardiovascular Disease CenterFuwai Central-China HospitalZhengzhou 450046China.

Objective:Arterial stiffness is an important predictor of cardiovascular disease.Microbial diversity in the gut has been shown to be associated inversely with arterial stiffness in Caucasian populations.However,due to the different profiles of the gut microbiota among ethnicities,the relationship between gut-microbiota dysbiosis and the progression of arterial stiffness merits further investigation.This study aimed to investigate the association between the composition and functional capacity of the gut microbiota and the progression of arterial stiffness.Methods:“Shotgun”metagenomics sequencing were undertaken in 96 individuals from a hypertension-associated gut-microbiota study in the Kailuan cohort,who measured brachial-ankle pulse wave velocity(baPWV)and provided fecal samples between September 2014 and February 2015 at Kailuan General Hospital and 11 affiliated hospitals.The different composition and functional capacity of the gut microbiota were compared between individuals without arterial stiffness(normal arterial stiffness group,baPWV<1,400 cm/s,n=27)and participants with arterial stiffness(increased arterial stiffness group,baPWV≥1,400 cm/s,n=69)at baseline.These participants were followed up prospectively for a mean duration of 2.6 years,and 50 underwent a repeat baPWV measurement.Associations between the gut microbiota and severity and progression of arterial stiffness were assessed using MaAsLin2 software after adjustment for age,sex,and mean arterial blood pressure and correction for multiple testing.Gene“catalogs”were aligned to the Kyoto Encyclopedia of Genes and Genomes(KEGG)database to obtain information for potential functional capacities of the gut microbiota.Results:In this study,14 genera and 50 species of bacteria were identified to be abundant in participants with normal arterial stiffness compared with those with increased arterial stiffness.Of 14 genera,the prevalence of beneficial bacteria of the genera Leadbetterella and Cytophaga was correlated inversely with baPWV(P<0.05).Analyses of

关键词： Arterial stiffness Brachial-ankle pulse wave velocity Gut microbiota Microbial functions

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Comparison of immediate changes of repolarization parameters after left bundle branch area pacing and traditional biventricular pacing in heart failure patients

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Chinese Medical Journal 2023年第7期136卷 868-870页

作者： Yao Li Wenzhao Lu Qingyun Hu Chendi Cheng Jinxuan Lin Yu’an Zhou Ruohan Chen Yan Dai Keping Chen Shu Zhang State Key Laboratory of cardiovascular Disease Arrhythmia CenterFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

To the Editor:Cardiac resynchronization therapy(CRT)is an effective treatment for advanced chronic heart failure(HF)patients with reduced ejection fraction.Despite its beneficial effects on cardiac function,traditiona... 详细信息

关键词： ventricular patients pacing

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Circulating MicroRNAs as Novel Diagnostic Biomarkers for Very Early-onset(≤40 years) Coronary Artery Disease

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Biomedical and Environmental Sciences 2016年第8期29卷 545-554页

作者： DU Ying YANG Sheng Hua LI Sha CUI Chuan Jue ZHANG Yan ZHU Cheng Gang GUO Yuan Lin WU Na Qiong GAO Ying SUN Jing DONG Qian LIU Geng LI Jian Jun Division of Dyslipidemia State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseaseCAMS and PUMC

Objective Very early-onset coronary artery disease （CAD） is a great challenge in cardiovascular medicine throughout the world, especially regarding its early diagnosis. This study explored whether circulating microRNAs （miRNAs） could be used as potential biomarkers for patients with very early-onset CAD. Methods We performed an initial screening of miRNA expression using RNA isolated from 20 patients with angiographically documented very early-onset CAD and 20 age- and sex-matched normal controls. For further confirmation, we prospectively examined the miRNAs selected from 40 patients with very early-onset CAD and 40 angiography-normal controls. Results A total of 22 overexpressed miRNAs and 22 underexpressed miRNAs were detected in the initial screening. RT-qPCR analysis of the miRNAs obtained from the initial screening revealed that four miRNAs including miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p exhibited significantly decreased expression in patients compared with that in controls （P〈0.05）. The areas under the receiver operating characteristic curve for these miRNAs were 0.824 （95% CI, 0.731-0.917; P〈0.001）, 0.758 （95% CI, 0.651-0.864; P〈0.001）, 0.753 （95% CI, 0.643-0.863; P〈0.001）, and 0.782 （95% CI, 0.680-0.884; P〈0.001）, respectively, in the validation set. Conclusion To our knowledge, this is an advanced study to report about four serum miRNAs （miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p） that could be used as novel biomarkers for the diagnosis of very early-onset CAD.

关键词： MicroRNA Biomarker Early-onset coronary artery disease

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室间隔切除术：治疗梗阻性肥厚型心肌病的金标准

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中华心血管病杂志 2009年第4期37卷 307-311页

作者： Joseph A Dearani Hartzell V Schaff Steve R Ommen Minnesota 55905 Division of Cardiovascular Surgery Mayo Clinic and Foundation Division of cardiovascular Diseases

梗阻性肥厚型心肌病（HCM）间隔切除术的治疗方法几乎与HCM文献报道同时出现。现在越来越清楚的表明，间隔切除术是一种缓解流出道梗阻症状最可靠的治疗方法。间隔切除术在HCM治疗中地位的不断提高，主要是因为：（1）对梗阻的患病率及... 详细信息

梗阻性肥厚型心肌病（HCM）间隔切除术的治疗方法几乎与HCM文献报道同时出现。现在越来越清楚的表明，间隔切除术是一种缓解流出道梗阻症状最可靠的治疗方法。间隔切除术在HCM治疗中地位的不断提高，主要是因为：（1）对梗阻的患病率及其影响认识更加清楚；（2）通过与酒精消融术的比较，使我们对该术式的认识更加清楚。下面我们介绍一下Mayo医院外科治疗HCM的经验。

关键词：梗阻性肥厚型心肌病治疗方法切除术金标准室间隔 HCM 梗阻症状外科治疗

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Macrophage CARD9 mediates cardiac injury following myocardial infarction through regulation of lipocalin 2 expression

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5383-5393页

作者： Yan Liu Yi-hui Shao Jun-meng Zhang Ying Wang Mei Zhou Hui-qin Li Cong-cong Zhang Pei-jie Yu Shi-juan Gao Xue-rui Wang Li-xin Jia Chun-mei Piao Jie Du Yu-lin Li Beijing Anzhen Hospital Capital Medical UniversityThe Key Laboratory of Remodeling-Related Cardiovascular DiseasesMinistry of EducationBeijing Collaborative Innovative Research Center for Cardiovascular DiseasesBeijing Institute of Heart Lung and Blood Vessel DiseasesBeijing100029China

Immune cell infiltration in response to myocyte death regulates extracellular matrix remodeling and scar formation after myocardial infarction(MI).Caspase-recruitment domain family member 9(CARD9)acts as an adapter that mediates the transduction of pro-inflammatory signaling cascades in innate immunity;however,its role in cardiac injury and repair post-MI remains unclear.We found that Card9 was one of the most upregulated Card genes in the ischemic myocardium of mice.CARD9 expression increased considerably 1 day post-MI and declined by day 7 post-MI.Moreover,CARD9 was mainly expressed in F4/80-positive macrophages.Card9 knockout(KO)led to left ventricular function improvement and infarct scar size reduction in mice 28 days post-MI.Additionally,Card9 KO suppressed cardiomyocyte apoptosis in the border region and attenuated matrix metalloproteinase(MMP)expression.RNA sequencing revealed that Card9 KO significantly suppressed lipocalin 2(Lcn2)expression post-MI.Both LCN2 and the receptor solute carrier family 22 member 17(SL22A17)were detected in macrophages.Subsequently,we demonstrated that Card9 overexpression increased LCN2 expression,while Card9 KO inhibited necrotic cell-induced LCN2 upregulation in macrophages,likely through NF-κ***2 KO showed beneficial effects post-MI,and recombinant LCN2 diminished the protective effects of Card9 KO in ***2 KO reduced MMP9 post-MI,and Lcn2 overexpression increased Mmp9 expression in macrophages.Slc22a17 knockdown in macrophages reduced MMP9 release with recombinant LCN2 treatment.In conclusion,our results demonstrate that macrophage CARD9 mediates the deterioration of cardiac function and adverse remodeling post-MI via LCN2.

关键词： CARD9 protective immunity

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Extracting and Measuring Uncertain Biomedical Knowledge from Scientific Statements

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Journal of Data and Information Science 2022年第2期7卷 6-30页

作者： Xin Guo Yuming Chen Jian Du Erdan Dong Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalBeijingChina NHC Key Laboratory of cardiovascular Molecular Biology and Regulatory Peptides BeijingChina Key Laboratory of Molecular cardiovascular Science Ministry of EducationBeijingChina Beijing Key Laboratory of cardiovascular Receptors research BeijingChina Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina Medical Informatics Center Peking UniversityBeijingChina National Institute of Health Data Science Peking UniversityBeijingChina Institute of cardiovascular Sciences Peking UniversityBeijingChina

Purpose:Given the information overload of scientific literature,there is an increasing need for computable biomedical knowledge buried in free text.This study aimed to develop a novel approach to extracting and measuring uncertain biomedical knowledge from scientific statements.Design/methodology/approach:Taking cardiovascular research publications in China as a sample,we extracted subject-predicate-object triples(SPO triples)as knowledge units and unknown/hedging/conflicting uncertainties as the knowledge context.We introduced information entropy(IE)as potential metric to quantify the uncertainty of epistemic status of scientific knowledge represented at subject-object pairs(SO pairs)levels.Findings:The results indicated an extraordinary growth of cardiovascular publications in China while only a modest growth of the novel SPO triples.After evaluating the uncertainty of biomedical knowledge with IE,we identified the Top 10 SO pairs with highest IE,which implied the epistemic status pluralism.Visual presentation of the SO pairs overlaid with uncertainty provided a comprehensive overview of clusters of biomedical knowledge and contending topics in cardiovascular research.research limitations:The current methods didn’t distinguish the specificity and probabilities of uncertainty cue words.The number of sentences surrounding a given triple may also influence the value of IE.Practical implications:Our approach identified major uncertain knowledge areas such as diagnostic biomarkers,genetic polymorphism and co-existing risk factors related to cardiovascular diseases in China.These areas are suggested to be prioritized;new hypotheses need to be verified,while disputes,conflicts,and contradictions need to be settled.Originality/value:We provided a novel approach by combining natural language processing and computational linguistics with informetric methods to extract and measure uncertain knowledge from scientific statements.

关键词： Uncertain knowledge Information entropy Natural language processing cardiovascular diseases China

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Emerging pathways of communication between the heart and non-cardiac organs

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The Journal of Biomedical research 2019年第3期33卷 145-155页

作者： Eugenio Hardy-Rando Carlos Fernandez-Patron Biotechnology Laboratory Study Center for Research and Biological EvaluationsInstitute of Pharmacy and FoodsUniversity of Havana Department ofBiochemistry Cardiovascular Research CentreMazankowski Alberta Heart InstituteFaculty of Medicine and DentistryUniversity of Alberta

The breakthrough discovery of cardiac natriuretic peptides provided the first direct demonstration of the connection between the heart and the kidneys for the maintenance of sodium and volume homeostasis in health and disease. Yet,little is still known about how the heart and other organs cross-talk. Here, we review three physiological mechanisms of communication linking the heart to other organs through: i) cardiac natriuretic peptides, ii) the microRNA-208 a/mediator complex subunit-13 axis and iii) the matrix metalloproteinase-2(MMP-2)/C-C motif chemokine ligand-7/cardiac secreted phospholipase A2(sPLA2) axis-a pathway which likely applies to the many cytokines, which are cleaved and regulated by MMP-2. We also suggest experimental strategies to answer still open questions on the latter pathway. In short, we review evidence showing how the cardiac secretome influences the metabolic and inflammatory status of non-cardiac organs as well as the heart.

关键词： heart liver metabolism inflammation natriuretic peptides microRNA matrix metalloproteinase

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Increased Transendothelial Cells Permeability Induced by Oxidized Lipoprotein(a) Relates to Reactive Oxygen Species Generation and Desmogleins Expression

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Chinese Journal of Biomedical Engineering(English Edition) 2016年第3期25卷 127-133页

作者： WANG Zuo YANG Jian ZHANG Xiao-lei MA Xiao-feng WANG Ren ZENG Jun-fa WEI Deng-heng ZHANG Kai LI Shuang LIN Xiao-long ZHAO Yue JIANG Zhi-sheng Institute of cardiovascular research Key Laboratory for Arteriosclerology of Hunan Province University of South China

Objective: This paper aims at measurement enhanced effect of oxidized lipoprotien(a) [ox Lp(a)] on permeability of monolayer endothelial cells and relationship with reactive oxygen species(ROS) generation and desmogleins(DSGs) expression.Methods and Results: Transendothelial permeability was assayed by transwell and reactive oxygen species(ROS) was determined by DCFH-DA staining. RT-PCR was carried out to determine DSGl and DSC2 expression in m RNA, respectively.Transendothelial permeability was enhanced by ox LP(a) dose and time dependently. The most marked effect appeared at a concentration of 100 mg/L, Transendothelial permeability reached the maximum value after 2 h of FITC-dextran addition, and then gradually decreased after 4 h. ox Lp(a) induces the generation of cellular reactive oxygen species(ROS), and this effect could be inhibited by superoxide dismutase(SOD).Incubation of HUVECs with ox Lp(a) resulted in a dose and time-dependent down-regulation of DSGl and DSC2 expression at transcriptional level. Conclusion:Permeability of monolayer endothelial cells was enhanced by ox Lp(a) which is related to up-regulating ROS formation and down-regulating desmogleins expression.

关键词： oxidized-lipoprotein(a) reactive oxygen species permeability desmogleins superoxide dismutase

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A novel β_(2)-AR agonist,Higenamine,induces β-arrestin-biased signaling

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Science China(Life Sciences) 2022年第7期65卷 1357-1368页

作者： Nana Zhang Haibo Zhu Zijian Li Erdan Dong State Key Laboratory for Bioactive Substances and Functions of Natural Medicines/Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study/Institute of Materia Medica Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital/Key Laboratory of Cardiovascular Receptors ResearchBeijing/Key Laboratory of Molecular Cardiovascular SciencesMinistry of Education/Key Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesMinistry of HealthBeijing 100191China

The biased ligands in G protein-coupled receptors(GPCRs)have opened new avenues for developing safer and more effective drugs.However,the identification of such biased ligands as drug candidates is highly desirable.Here,we report that Higenamine,a compound isolated from a Chinese herb,functions as a novel β-arrestin-biased ligand of the β_(2)-adrenergic receptor(β_(2)-AR).The radioligand binding assays demonstrated that Higenamine was the ligand of β_(2)-AR.Higenamine induced phosphorylation of extracellular signal-regulated kinase 1/2(ERK1/2),which can be blocked by propranolol,an inhibitor of β_(2)-AR.The Gi protein inhibitor,pertussis toxin,had no effect on the phosphorylation of ERK1/2 induced by Higenamine.Furthermore,Higenamine induced ERK1/2 phosphorylation through transactivation of Epithelial growth factor receptor(EGFR).We also found that Higenamine-induced-ERK1/2 phosphorylation is dependent on β-arrestin1/2,and HG inhibits Doxorubicin-induced cardiomyocyte apoptosis.Our results identify Higenamine as a novel biased ligand via the β-arrestin-dependent pathway.These findings give us a better understanding of Higenamine’s potential role in designing diagnostic and therapeutic strategies.

关键词： Higenamine β_(2)-adrenergic receptor β-arrestin-biased signaling extracellular signal-regulated kinase 1/2

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