1.Conserved translational control in cardiac hypertrophy revealed by ribosome profiling.
Bao-Sen WANG ; Jian LYU ; Hong-Chao ZHAN ; Yu FANG ; Qiu-Xiao GUO ; Jun-Mei WANG ; Jia-Jie LI ; An-Qi XU ; Xiao MA ; Ning-Ning GUO ; Hong LI ; Zhi-Hua WANG
Acta Physiologica Sinica 2025;77(5):757-774
A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals
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Humans
;
Cardiomegaly/physiopathology*
;
Ribosomes/physiology*
;
Protein Biosynthesis/physiology*
;
Mice
;
Cardiomyopathy, Dilated/genetics*
;
Ribosome Profiling
2.Network Meta-analysis of comparative efficacy of Chinese medicine injections for dilated cardiomyopathy.
Shi-Yi TAO ; Lin-Tong YU ; Jun LI ; Yong-Hao LI ; Xuan-Chun HUANG ; Tian-Tian XUE ; De-Shuang YANG ; Chao-Nan ZHENG
China Journal of Chinese Materia Medica 2024;49(22):6198-6213
Bayesian network Meta-analysis was conducted to assess the efficacy and safety of different Chinese medicine injections for dilated cardiomyopathy(DCM). CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, Cochrane Library, ProQuest, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov were searched for the randomized controlled trial(RCT) from the inception to January 2024. The quality of the included RCT was evaluated using the Cochrane's risk of bias assessment tool, and the quality of evidence for outcomes was assessed by GRADE. Stata 16.0 and RevMan 5.4 softwares were used for Meta-analysis. A total of 57 RCTs involving 4 812 subjects, 6 Chinese medicine injections and 6 outcome indicators were included. Bayesian network Meta-analysis indicated that:(1) In terms of increasing clinical total effectiveness rate, except Shenqi Fuzheng Injection + conventional western medicine, other 5 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Xinmailong Injection + conventional western medicine had the best effect.(2) In terms of improving left ventricular ejection fraction, all of the 6 Chinese medicine injections combined with conventional western medicine were superior to conventional western medicine alone, and Shengmai Injection + conventional western medicine had the highest likelihood of being the best intervention.(3) On account of reducing left ventricular end-diastolic dimension, Shenfu Injection + conventional western medicine, Shenmai Injection + conventional western medicine, Huangqi Injection + conventional western medicine, and Xinmailong Injection + conventional western medicine outperformed conventional western medicine alone except Shengmai Injection + conventional western medicine, and Huangqi Injection + conventional western medicine had the highest probability of being the best treatment.(4) In terms of decreasing BNP, Huangqi Injection + conventional western medicine, Shenfu Injection + conventional western medicine, and Shenmai Injection + conventional western medicine were better than conventional western medicine alone, and Huangqi Injection + conventional western medicine had the highest likelihood of being the best treatment.(5) Considering the improvement in 6-min walk test, Shenmai Injection + conventional western medicine were superior to conventional western medicine alone.(6) In the case of improving cardiac output, Shenmai Injection + conventional western medicine, Shengmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine, and Shenqi Fuzheng Injection + conventional western medicine outperformed conventional western medicine alone except Shenfu Injection + conventional western medicine, thereinto, Shenmai Injection + conventional western medicine might be the optimal choice for increasing cardiac output level.(7) For safety, no statistically significant difference in adverse events was recorded between the experimental group and the control group(P=0.24). Bayesian network Meta-analysis showed that the addition of Chinese medicine injections to conventional western medicine exerted a more positive effect for DCM, and had advantages in alleviating clinical symptoms and improving cardiac function. However, due to the overall low quality of the included articles, the low inclusion of certain Chinese medicine injections, and the lack of direct comparison between different Chinese medicine injections, the results need to be further confirmed.
Humans
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Bayes Theorem
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Cardiomyopathy, Dilated/physiopathology*
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Drugs, Chinese Herbal/administration & dosage*
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Injections
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Randomized Controlled Trials as Topic
;
Treatment Outcome
4.Prognostic Significance of Frontal QRS-T Angle in Patients with Idiopathic Dilated Cardiomyopathy.
Sheng-Na LI ; Xin-Lin ZHANG ; Guo-Long CAI ; Ruo-Wei LIN ; He JIANG ; Jian-Zhou CHEN ; Biao XU ; Wei HUANG
Chinese Medical Journal 2016;129(16):1904-1911
BACKGROUNDCurrent risk stratification of idiopathic dilated cardiomyopathy (IDC) lacks sufficient sensitivity and specificity. The objective of this study was to investigate the predictive role of frontal QRS-T angles in IDC.
METHODSA prospective study with 509 IDC patients was performed from February 2008 to December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up was conducted every 6 months. Analyses by Cox Proportional Hazards model were performed to evaluate the association between QRS-T angle and outcomes. The primary outcome of interest was all-cause mortality.
RESULTSDuring a median follow-up of 34 months, 90 of 316 patients with QRS-T angles >90° died compared to 31 of 193 patients with QRS-T angles ≤90° (hazard ratio [HR] =2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR = 2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05), cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR = 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T angle (100.9 ± 53.4° vs. 107.2 ± 54.4°, P < 0.001). The frontal QRS-T angle correlated well with established risk factors, such as left ventricular ejection fraction, brain natriuretic peptide, and New York Heart Association functional class.
CONCLUSIONSThe frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation.
Aged ; Cardiomyopathy, Dilated ; pathology ; physiopathology ; Electrocardiography ; Female ; Heart Failure ; pathology ; physiopathology ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors
5.Relationship between Myocardial Extracellular Space Expansion Estimated with Post-Contrast T1 Mapping MRI and Left Ventricular Remodeling and Neurohormonal Activation in Patients with Dilated Cardiomyopathy.
Ji Hyun YOON ; Jung Woo SON ; Hyemoon CHUNG ; Chul Hwan PARK ; Young Jin KIM ; Hyuk Jae CHANG ; Geu Ru HONG ; Tae Hoon KIM ; Jong Won HA ; Byoung Wook CHOI ; Se Joong RIM ; Namsik CHUNG ; Eui Young CHOI
Korean Journal of Radiology 2015;16(5):1153-1162
OBJECTIVE: Post-contrast T1 values are closely related to the degree of myocardial extracellular space expansion. We determined the relationship between post-contrast T1 values and left ventricular (LV) diastolic function, LV remodeling, and neurohormonal activation in patients with dilated cardiomyopathy (DCM). MATERIALS AND METHODS: Fifty-nine patients with DCM (mean age, 55 +/- 15 years; 41 males and 18 females) who underwent both 1.5T magnetic resonance imaging and echocardiography were enrolled. The post-contrast 10-minute T1 value was generated from inversion time scout images obtained using the Look-Locker inversion recovery sequence and a curve-fitting algorithm. The T1 sample volume was obtained from three interventricular septal points, and the mean T1 value was used for analysis. The N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level was measured in 40 patients. RESULTS: The mean LV ejection fraction was 24 +/- 9% and the post-T1 value was 254.5 +/- 46.4 ms. The post-contrast T1 value was significantly correlated with systolic longitudinal septal velocity (s'), peak late diastolic velocity of the mitral annulus (a'), the diastolic elastance index (Ed, [E/e']/stroke volume), LV mass/volume ratio, LV end-diastolic wall stress, and LV end-systolic wall stress. In a multivariate analysis without NT-proBNP, T1 values were independently correlated with Ed (beta = -0.351, p = 0.016) and the LV mass/volume ratio (beta = 0.495, p = 0.001). When NT-proBNP was used in the analysis, NT-proBNP was independently correlated with the T1 values (beta = -0.339, p = 0.017). CONCLUSION: Post-contrast T1 is closely related to LV remodeling, diastolic function, and neurohormonal activation in patients with DCM.
Adult
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Aged
;
Algorithms
;
Blood Pressure
;
Cardiomyopathy, Dilated/*diagnosis/radiography
;
Echocardiography
;
Extracellular Space/physiology/*radiography
;
Female
;
Heart Ventricles/physiopathology/radiography
;
Humans
;
Magnetic Resonance Imaging
;
Male
;
Middle Aged
;
Multivariate Analysis
;
Natriuretic Peptide, Brain/analysis
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Peptide Fragments/analysis
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*Ventricular Remodeling
6.Adverse effects of type B ventricular pre-excitation on ventricular wall motion and left ventricular function: clinical analysis of 9 cases.
Baojing GUO ; Chencheng DAI ; Wenxiu LI ; Yanyan XIAO ; Ling HAN
Chinese Journal of Pediatrics 2014;52(4):308-312
OBJECTIVETo analyze the adverse effects of type B ventricular pre-excitation on ventricular wall motion and left ventricular function and its clinical characteristic.
METHODThe clinical, electrophysiological and echocardiographic characteristics of the 9 cases with type B ventricular pre-excitation before and after ablation seen between March 2011 and March 2013 were analyzed. The patients aged from 3 to 16 years. Five of them were female.
RESULTDyschronous left ventricular contraction was demonstrated by M-Mode echocardiography in all of the cases. The basal segments of the interventricular septum turned thin and moved in a manner similar to that of an aneurysm, with typical bulging during end-systole, which was observed in six cases. All patients received successful RFCAs. The locations of the accessory pathways (APs) were the right-sided anteroseptum (n = 2) and the free wall (n = 7). Their physical activities and growth improved greatly in the four cases with coexisting dilated cardiomyopathy (DCM). The echocardiographic data demonstrated that their LV contraction recovered to synchrony shortly after the ablation, LVEF recovered to normal and LVED decreased to almost normal gradually during the follow-up.
CONCLUSIONOvert right-sided APs may have adverse effects on ventricular wall motion and left ventricular function. They can even result in DCM. Dyssynchronous ventricular contraction induced by right-sided overt accessory pathway may be the vital mechanism. Such kinds of cases are indication for ablation with good prognosis.
Adolescent ; Cardiomyopathy, Dilated ; diagnostic imaging ; etiology ; physiopathology ; Catheter Ablation ; Child ; Child, Preschool ; Echocardiography ; Female ; Heart Ventricles ; physiopathology ; Humans ; Male ; Myocardial Contraction ; Ventricular Dysfunction, Left ; diagnostic imaging ; etiology ; physiopathology ; Wolff-Parkinson-White Syndrome ; complications ; physiopathology
7.Correlations among persistent viral infection, heart function and Chinese medicine syndromes in dilated cardiomyopathy patients.
Qiang LIU ; Xiao-Jia SU ; Yan YU ; Yong-Lin LIU
Chinese journal of integrative medicine 2014;20(12):928-933
OBJECTIVETo investigate the correlations among persistent viral infection, heart function and Chinese medicine (CM) difined-syndromes in patients with dilated cardiomyopathy (DCM).
METHODSFifty patients with DCM in the First Affiliated Hospital of Zhejiang Chinese Medical University from October 2009 to December 2011 were selected as the research subjects, and 30 healthy people were simultaneously selected as the normal control group to detect persistent viral infections after admission. The CM syndrome type and grade of heart function were then evaluated. The expression level of Coxsackie adenovirus receptor (CAR) was detected using the flow cytometry (FCM) technique, coxsackie virus RNA (CVB-RNA) using reverse transcription polymerase chain reaction (RTPCR), and the plasma brain natriuretic peptide (BNP) level with a Triage meter plus diagnosis instrument. Finally, the parameters such as left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by ultrasonic cardiogram. Person correlation analysis was used for measured data, Spearman correlation analysis for rating data, and the Chi-square test for numerical data.
RESULTSCVB-RNA was positive in 22 patients (44%) with DCM, while only 6 cases (20%) were CVB-RNA-positive in the normal control group, with a significant difference between the two groups (P<0.01). The expression level of CAR was significantly elevated in the DCM group compared with the normal control group (P<0.01). In CVB-RNA-positive patients (22 cases), the expression level of CAR was significantly higher than in CVB-RNA-negative patients (28 cases; P<0.01). In the DCM patients, there was a positive correlation between the CAR expression and the BNP level (r=0.34, P<0.05), while no significant difference was found between the CAR expression and the LVEF and LVEDd (r=-0.32, 0.30, P>0.05). There was no clear correlation between virus infection and the CM syndrome types in DCM patients (r=-0.22, P>0.05). According to the sequence of syndrome types: phlegm → qi deficiency → blood stasis → hydroretention with asthenic yang (from low to high), a positive correlation was existed between the BNP levels and CM syndrome types (r=0.139, P<0.05).
CONCLUSIONThe expression of CAR on the surface of white cells could be used to detect persistent viral infection. The expression level of CAR and heart function in DCM patients were highly correlated. The expression level of BNP may serve as an objective index for differentiating CM syndromes for patients with DCM.
Adult ; Aged ; Cardiomyopathy, Dilated ; blood ; complications ; physiopathology ; virology ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Coxsackievirus Infections ; blood ; complications ; physiopathology ; Female ; Heart Function Tests ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; RNA, Viral ; blood ; Syndrome
8.Changes of heart-type fatty acid-binding protein in children with chronic heart failure and its significance.
Yu-Ping SUN ; Wen-Di WANG ; Shao-Chun MA ; Li-Yan WANG ; Ling-Yan QIAO ; Li-Ping ZHANG
Chinese Journal of Contemporary Pediatrics 2013;15(2):99-101
OBJECTIVETo study serum levels of heart-type fatty acid-binding protein (h-FABP) in children with chronic heart failure (CHF), and the correlation between heart function and the level of h-FABP, with the aim of studying the significance of h-FABP in CHF.
METHODSThirty-six children with CHF, including 16 cases of endocardial fibroelastosis (EFE) and 20 cases of dilated cardiomyopathy (DCM) were enrolled in the study. Thirty healthy children sevred as the control group. Serum levels of h-FABP were determined using ELISA, and left ventricular ejection fraction (LVEF), cardiac index (CI) and fractional shortening of the left ventricle (LVSF) were measured by two-dimensional echocardiography in the CHF group.
RESULTSMean levels of h-FABP in the CHF group were significantly higher than in the control group (21.7±4.3 ng/mL vs 6.2±1.7 ng/mL; P<0.01). The worse the heart function, the higher the h-FABP levels (P<0.01). Mean levels of h-FABP in both the EFE and DCM groups were significantly higher than in the control group (P<0.01). Serum h-FABP concentrations were negatively correlated with LVEF, CI and LVSF (r=-0.65, -0.64 and -0.71 respectively; P<0.01) in the CHF group.
CONCLUSIONSSerum h-FABP levels increase in children with CHF and are closely related to the severity of the condition. Serum h-FABP levels can be used as a biomarker for the diagnosis of heart failure and the evaluation of its severity.
Cardiomyopathy, Dilated ; blood ; Child ; Child, Preschool ; Chronic Disease ; Endocardial Fibroelastosis ; blood ; Fatty Acid Binding Protein 3 ; Fatty Acid-Binding Proteins ; blood ; Female ; Heart Failure ; blood ; physiopathology ; Humans ; Infant ; Male ; Severity of Illness Index
9.Reversible dilated cardiomyopathy caused by idiopathic hypoparathyroidism.
Youn Joo JUNG ; Sung Eun KIM ; Ji Yeon HONG ; Jun Hee LEE ; Dae Gyun PARK ; Kyoo Rok HAN ; Dong Jin OH
The Korean Journal of Internal Medicine 2013;28(5):605-608
Dilated cardiomyopathy (DCM) is usually an idiopathic disease with a poor prognosis. Hypocalcemia is a rare and reversible cause of DCM. Here, we report a 50-year-old female with DCM, induced by idiopathic hypoparathyroidism, that improved after treatment with calcium.
Calcium/administration & dosage
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Cardiomyopathy, Dilated/diagnosis/*etiology/physiopathology
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Dietary Supplements
;
Electrocardiography
;
Female
;
Humans
;
Hypocalcemia/diagnosis/drug therapy/*etiology
;
Hypoparathyroidism/*complications/diagnosis/drug therapy
;
Middle Aged
;
Recovery of Function
;
Treatment Outcome
;
Vitamin D/administration & dosage
10.Quantification of left and right ventricular systolic function in patients with dilated cardiomyopathy using real-time three-dimensional echocardiography.
Kai TONG ; Jin ZHANG ; Jing WANG ; Xiao ZHOU ; Xiao LEI ; Yong XU ; Guang ZHI
Journal of Central South University(Medical Sciences) 2012;37(6):561-566
OBJECTIVE:
To assess left and right ventricular systolic function in patients with dilated cardiomyopathy (DCM) using real-time three-dimensional echocardiography (RT-3DE).
METHODS:
Fifty DCM patients and 50 normal subjects were enrolled. Left and right ventricular systolic function parameters including end-systolic volume (ESV) and end-diastolic volume (EDV), stroke volume (SV) and ejection fraction (EF) were measured with RT-3DE. The systolicdyssynchrony index (SDI) for left ventricular systolic function was also measured in the same time. The study compared the data of the left and right ventricular systolic function parameters between the DCM group and the control group. Cardiac magnetic resonance (CMRI) was performed in a subgroup of the 30 DCM patients to confirm RT-3DE measurements.
RESULTS:
The results of EDV, ESV and SDI measured by RT-3DE were significantly higher in patient group with DCM than those in the control group (P<0.001). The result of EF was significantly lower in patients with DCM than in normal subjects (P<0.001), but SV showed no significant difference between the two groups (P>0.05). In the DCM group, the results showed a significantly negative correlation between left ventricular ejection fraction (LVEF) and SDI (r=-0.697, P<0.001), and there was also a moderate correlation between LVEF and right ventricular ejection fraction (RVEF) (r=0.496, P<0.01). The results of ESV, EDV and EF showed no significant differences as measured by RT-3DE or CMRI in the patient group (P>0.05), and there was also good correlation between the two measurements (LVEF: r=0.89, P<0.01; RVEF: r=0.85, P<0.01).
CONCLUSION
Left and right ventricular systolic function in DCM could be evaluated by RT-3DE with left and right ventricular systolic function parameters.
Adult
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Aged
;
Cardiomyopathy, Dilated
;
diagnostic imaging
;
physiopathology
;
Case-Control Studies
;
Echocardiography, Three-Dimensional
;
methods
;
Female
;
Heart Ventricles
;
diagnostic imaging
;
Humans
;
Male
;
Middle Aged
;
Stroke Volume
;
Systole
;
Ventricular Function, Left
;
physiology
;
Ventricular Function, Right
;
physiology

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