Table of Content

30 June 2016, Volume 22 Issue 3

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Cardiac remodeling and regeneration: the spotlight in cardiovascular research

2016, 22(3):  261-264.  doi:10.3969/j.issn.1007-2861.2016.04.020

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Cardiac remodeling and regeneration: the spotlight in cardiovascular research

Circulating miRNAs predict response to cardiac resynchronization therapy

WANG Fei, Saumya Das

2016, 22(3):  265-269.  doi:10.3969/j.issn.1007-2861.2016.04.019

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Heart failure (HF) is one of the most common syndrome seriously harmful to human health. Cardiac resynchronization therapy (CRT) is an exciting recent advancement for HF patient by targeting ventricular systolic dyssynchrony, but it has been proved that CRT cannot achieve hemodynamic or clinical benefit for all patients. It is very essential to find out biomarkers for predicting responsive patients. Circulating extracellular microRNAs(miRNAs) have emerged as novel biomarkers for many diseases. Recent study indicated that a high level of circulating miR-30d could predict response to CRT, which may have bright prospects in future research and application.

Gene therapy for cardiovascular disease

DING Qiurong, CHEN Yanhao

2016, 22(3):  270-279.  doi:10.3969/j.issn.1007-2861.2016.03.013

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Gene therapy shows great promise in the treatment of both inherited and acquired cardiovascular diseases. Identification of key molecule players in pathophysiology of cardiovascular disease and development of human disease genomic research lead to encouraging preclinical gene therapy studies in animal models. However, the presence of cellular immune responses, insufficient gene expression level and overall limited in vivo gene transduction efficiencies have hampered the translational progress to clinical use of gene therapy. In recent years, improvements in gene delivery system and discovery of advanced genome editing technologies open new therapeutic perspectives, with clustered regularly interspaced short palindromic repeats (CRISRP)/Cas9 genome editing technology already being successfully used in animal models to treat hypercholesterolemia. Further improvement in gene delivery efficiency, increase in targeting specificity of genome editing tools, and establishment of experimental systems for a thorough analysis of potential safety problems would help eventually bring gene therapy for heart disease to reality. In this review, recent advances in the use of different delivery vectors and CRISPR/Cas9 genome editing technology in gene therapy research to treat cardiovascular diseases are discussed.

Stem cells and cardiac regeneration

GONG Hui, CHEN Zhidan, ZOU Yunzeng

2016, 22(3):  280-284.  doi:10.3969/j.issn.1007-2861.2016.03.016

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Human myocardium has poor regenerative power, and significant myocardial injury results in irreversible damage, remodeling, and dysfunction. Stem cells enable promising regenerative strategies for cardiovascular diseases. The search for suitable stem cell phenotypes that will improve myocardial regenerative ability needs better understanding of the molecular mechanisms of repair and regeneration. Previous reports have suggested that several stem phenotypes regulate myocardial regeneration in vitro and in vivo. This review describes the therapeutic potential of mesenchymal stem cell (MSC) therapy in terms of angiogenic and regenerative capacity after myocardial infarction. In addition, the effect of cardiac side population cells (CSPs) and the differentiation of induced pluripotent stem cells (iPSCs) in cardiac regeneration are discussed. The review provides recent data and helps broaden therapeutic potential and clinical impact of stem cell therapy.

Induced pluripotent stem cells in cardiac regeneration

HU Shijun1,2, YU You1,2, FANG Xing1,2, LEI Wei1,2, ZHAO Zhen’ao1,2

2016, 22(3):  285-292.  doi:10.3969/j.issn.1007-2861.2016.04.001

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Induced pluripotent stem cells (iPSCs) have emerged as a novel tool for cell therapy for cardiovascular diseases. iPSCs are functionally similar to embryonic stem cells (ESCs) while avoiding ethical issues and immune rejection. Given limited regenerative ability of human heart following cardiovascular diseases cardiovascular cells derived from iPSCs have been considered as a promising cell source in cardiovascular regenerative therapy. This paper summarizes and discusses the iPSCs technology and its potential regenerative applications in cardiac regeneration.

Exercise-induced cardiac regeneration: new therapeutic strategy for cardiovascular diseases

BEI Yihua, XIAO Junjie

2016, 22(3):  293-301.  doi:10.3969/j.issn.1007-2861.2016.03.018

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Adult mammalian heart has limited regenerative capacity, obviously insufficient to recover cardiomyocyte loss after injury. Exercise can induce cardiac regeneration, not only through promoting cardiomyocyte hypertrophy and renewal while reducing apoptosis, but also through modulating the functions of endothelial cells and fibroblasts. IGF-1/PI3K/Akt signaling, C/EBPβ/CITED4 transcription factors and nitric oxide are essential molecular mechanisms mediating exercise-induced cardiac regeneration. In addition increasing interests are focused on the roles of microRNAs, considered as important biomarkers, in exercise-induced cardiac regeneration. More importantly, exercise-induced cardiac regeneration protects against myocardial infarction, ischemia-reperfusion injury, metabolic cardiomyopathy, and aging-related myocardial injury. Exercise-induced cardiac regeneration may be a potential therapeutic strategy for cardiovascular diseases.

Non-coding RNAs mediate cardiac remodeling and regeneration

GAO Feng1,2, CHEN Jinghai1,2

2016, 22(3):  302-309.  doi:10.3969/j.issn.1007-2861.2016.03.021

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Recently, more and more evidences indicate that a large number of non-coding RNAs (ncRNAs) are involved in gene expression, physiological and pathological regulation, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Cardiac remodeling and regeneration are key to cardiovascular biology and diseases. Regulation of gene expression during cardiac remodeling and regeneration is complicated, involving epigenetic, transcriptional, post-transcriptional and translational regulation. In the past decade, miRNAs have drawn much attention for their impact on cardiovascular diseases and regeneration. miRNAs negatively regulate the expression of the target genes through post-transcriptional regulation. Recent research uncovered that lncRNAs play an important role in cardiac development and diseases, involving epigenetic, transcriptional and post-transcriptional regulation, making lncRNAs become another group of key regulatory non-coding RNAs. This paper summarizes the recent progress in the study of non-coding RNAs in cardiac remodeling and cardiac regeneration.

Non-coding RNAs and myocardial remodeling

WANG Jianxun1, GAO Jinning1, DING Wei2

2016, 22(3):  310-317.  doi:10.3969/j.issn.1007-2861.2016.04.002

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Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not encode proteins. Studies show that ncRNAs are not only involved in cell proliferation, apoptosis, differentiation, metabolism and other physiological processes, but also in pathogenesis of diseases. Myocardial remodeling is the main pathological basis of a variety of cardiovascular diseases. Many studies have shown that occurrence and development of myocardial remodeling are closely related to the regulation of ncRNAs. Recent researches of ncRNAs in heart disease have achieved rapid advances. Aimed to look for new targets for heart disease treatment, this paper systematically introduces the latest research progress, mainly in the mechanism of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in myocardial remodeling.

Application of sonosensitizers derived from Chinese herb products in sonodynamic therapy for atherosclerosis treatment

KOU Jiayuan1, JIANG Yueqing1, TIAN Ye1,2, YANG Liming1

2016, 22(3):  318-325.  doi:10.3969/j.issn.1007-2861.2016.03.012

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At present, morbidity of cardiovascular disease induced by atherosclerosis (AS) is becoming higher. Besides expensive intervention and bypass surgery, it is extremely urgent to look for a popular and effective method for the treatment of AS. Sonodynamic therapy (SDT) is a non-invasive targeting therapy, and is promising for AS treatment based on the SDT-related research. Sonosensitizer, an application of SDT, is an entry points of the SDT investigation. Therefore, different sonodynamic effects with different sonosensitizers are investigated by researchers in AS treatment. In recent years, it is found that sonosensitizers derived from Chinese herb products play an important role in SDT, exerting potent sonodynamic effects for AS treatment. This review briefly summarizes the action of SDT and relevant development of SDT with emodin, curcumin, hypericin and its derived derivatives as sonosensitizers for AS treatment.

Advances of transcription factor Bach1 in cardiovascular diseases

JIA Mengping, GUO Jieyu, MENG Dan

2016, 22(3):  326-330.  doi:10.3969/j.issn.1007-2861.2016.03.014

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BTB and CNC homology 1 (Bach1) is a transcription factor widely existing in most tissues of mammals. Bach1 negatively regulates various antioxidant gene such as heme oxygenase-1 (HO-1), involving oxidative stress. Knockout of Bach1 has a protective effect on myocardial ischemia reperfusion injury. Recent research found that Bach1 inhibits the Wnt/b-catenin signaling pathway and angiogenesis in hindlimb ischemia of mice. This paper focuses on the research of Bach1 in cardiovascular diseases.

Slit-Robo signal pathway in cardiovascular development

ZHANG Bing, FU Yi

2016, 22(3):  331-335.  doi:10.3969/j.issn.1007-2861.2016.03.009

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Slit-Robo pathway has recently been shown to be vital in cardiovascular development and regeneration. Slit3, a proangiogenic factor, regulates angiogenesis and organ formation in embryonic development by binding to its receptor Robo4. Activation of Slit3-Robo4 promotes formation of vascular network in engineered tissues. Heparan sulfate regulates the development of blood vessel and diaphragm through modulating the Slit3-Robo4 signal pathway. Moreover, the Slit-Robo signal pathway plays an essential role in developing cardiac systematic venous return and pericardium. Deficiency of Slit3 leads to developmental defect of other organs such as kidney and ureter. Therefore, further understanding of the Slit3-Robo4 signal pathway in the future may provide a theoretical foundation and therapeutic targets for prevention and therapy of cardiovascular and related diseases.

Macrophage migration inhibitory factor deficiency aggravates cardiac hypertrophy induced by phenylephrine in mice

XIAO Zhen, ZHU Jiening, TANG Chunmei, LIN Qiuxiong, HU Zhiqin, ZHANG Zhuo, FU Yongheng, ZHANG Mengzhen, SHAN Zhixin

2016, 22(3):  336-343.  doi:10.3969/j.issn.1007-2861.2016.03.011

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To investigate the effect of macrophage migration inhibitory factor (MIF) deficiency on the cardiac hypertrophy induced by hypodermic injection of phenylephrine (PE) in mice. A mouse model of cardiac hypertrophy induced by hypodermic injection of PE was established based on MIF-knockout (MIF-KO) mouse and the wide type control (WT) mouse. The left ventricular (LV) structure and function variables were assessed by transthoracic echocardiography. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay was performed to detect cardiomyocyte apoptosis. Expressions of SOD1, SOD2 and Trx2 were determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blot assay, respectively. ①A mouse model of cardiac hypertrophy was achieved, induced by hypodermic injection of 20 mg/(kg·d) PE for 3 d. Compared with WT mice, PE injection induced more severe cardiac hypertrophy in MIF-KO mice. ②TUNEL assay revealed that the level of PE injection-induced cardiomyocte apoptosis in the myocardium of MIF-KO mouse was higher than that in WT mice. ③Expressions of SOD1 and Trx2 were significantly decreased in the myocardium of MIF-KO mice after PE injection, and reduction of Trx2 protein in myocardium of MIF-KO mice was more than that in WT mouse. MIF deficiency attenuates the expressions of SOD1 and Trx2, contributing to the aggravation of cardiomyocyte apoptosis and cardiac hypertrophy induced by hypodermic injection of PE in mice.

Effects of exercise on cardiac function and differential expression of circulating miRNAs in rats with acute myocardial infarction

XIA Kun1, DING Rongjing2, LU Kai3, WANG Li4

2016, 22(3):  344-356.  doi:10.3969/j.issn.1007-2861.2016.03.010

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To study the effects of different exercise intensity on cardiac function and differential expression of circulating microRNAs (miRNAs), target genes and gene function in rats with acute myocardial infarction (AMI). Establish AMI models with 40 rats, divide them into 4 groups, such as Sham operation group, isolated myocardial infarction group, continuous moderately training (CMT) group, and high intensity interval training (HIT) group, with 10 AMI rats in each group. CMT and HIT groups received exercise therapies for 8 weeks. Evaluate cardiac function with echocardiography. Analyze differential expression of circulating microRNAs, related target genes and gene function using miRNAs microarray and bioinformatics technology. CMT and HIT therapies significantly improved cardiac function and exercise tolerance in AMI rats. The effect of HIT group is significantly better than that of CMT group. Compared with Sham operation group, 14 circulating miRNAs were obviously up-regulated, 4 circulating miRNAs were obviously down-regulated in isolated myocardial infarction group. Compared with isolated myocardial infarction group, 11 circulating miRNAs were obviously up-regulated, 2 circulating miRNAs were obviously down-regulated in CMT group, and 53 circulating miRNAs were obviously up-regulated, 41 key miRNAs were obviously down-regulated in HIT group. Compared with Sham operation group, differential expression of myocardium related circulating miRNAs in isolated myocardial infarction group are miR-26a-5p, miR-92a-3p and miR-378a-3p. Compared with isolated myocardial infarction group, there is miR-92a-3p in CMT group, and there are miR-34c-3p, miR-23a-3p, miR-98-3p, miR-208a-5p and miR-92-3p in HIT group. HIT improving cardiac function and exercise tolerance in AMI rats are better than those of CMT. Numbers of differential expression of circulating miRNAs and myocardium related circulating miRNAs with HIT are higher than those of CMT, indicating that circulating miRNAs are expected to be biomarkers for determining exercise intensity and exercise effect.

Effects of Chinese patent medicines on left ventricular ejection fraction and brain natriuretic peptide in patients with chronic heart failure: systematic review#br# and Meta-analysis

LIU Shuo1, LI Min1, CHEN Shiqi1, QIU Ruijin1, ZHANG Qin1, ZHAO Mingjing1, CHEN Jing2, SHANG Hongcai1

2016, 22(3):  357-365.  doi:10.3969/j.issn.1007-2861.2016.03.017

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To evaluate efficacy and security of Chinese patent medicines on left ventricular ejection fraction (LVEF) and plasma brain natriuretic peptide (BNP) in the treatment of heart failure (HF). Five databases including PubMed, The Cochrane Library, CNKI, VIP and WanFang Data have been searched to identify relevant randomized controlled trials (RCTs) up till March 2016. Methodological quality of the included studies was assessed using criteria from Cochrane Reviewer’s Handbook 5.3, and analyzed using Rev Man 5.3 software. Sixteen RCTs of Chinese patent medicines were included. Results of the Meta-analysis showed that Chinese patent medicines were more effective on LVEF (MD=5.80, 95%CI (confidence interval): 0.236.73, P < 0.01) and BNP (MD= −366.99, 95%CI: −412.00  −321.97, P < 0.01). In addition, assessed quality of the included randomized controlled trials were low. Based on low quality and limited data, Chinese patent medicines were more significant at the LVEF and BNP level. Therefore, sufficient high quality experiments need to be conducted to confirm efficacy and security of Chinese patent medicines.

Circulating miR-21-3p as biomarkers for sepsis-induced cardiomyopathy

LIU Hui, WANG Hui, SHI Jing, KONG Xiangqing

2016, 22(3):  366-370.  doi:10.3969/j.issn.1007-2861.2016.03.019

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Recently, microRNAs(miRNAs) are found to be abundantly present in body fluids including plasma and serum, and called circulating miRNAs. Increasing evidences suggest that circulating miRNAs may be useful as stable blood-based biomarkers in sepsis. Serum miR-21-3p is significantly increased in septic patients compared with healthy controls. Receiver operating characteristic (ROC) curve analyses suggest that these plasma miR-21-3p may be useful biomarkers for discriminating patients with sepsis-induced cardiomyopathy (SIC) from healthy controls. miR-21-3p yields the ROC area under the curve
(AUC) of 0.949. Further analyses indicate that the expression level of miR-21-3p is correlated with the brain natriuretic peptide (BNP) (r = 0.968, P < 0.001) and cardiac troponin T (cTNT) level (r = 0.257, P = 0.002). Serum miR-21-3p may serve as new biomarkers for sepsis with high specificity and sensitivity.

Influence of alprostadil on preventing left ventricular remodeling after acute myocardial infarction

ZHAN Li1,2, XU Jiahong1

2016, 22(3):  371-375.  doi:10.3969/j.issn.1007-2861.2016.03.015

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To investigate the clinic effect of alprostadil on preventing left ventricular remodeling after acute myocardial infarction (AMI). A total of 73 cases of AMI were randomly divided into two groups: basic treatment group and alprostadil treatment group. Both groups were given basic treatments such as rest, oxygen inhalation, dual antiplatelet therapy. Alprostadil was intravenously injected in the alprostadil treatment group, 10 μg once a day for 7 days. Left ventricular end-diastolic dimension (LVDd), left ventricular end-systolic dimension (LVDs), interventricular septal thickness (IVST), left ventricle posterior wall end-diastolic (LVPWd), ejection fraction (EF) and E/A ratio were measured by echocardiography on the 3rd and the 28th days after treatment. Compared to the 3rd day after treatment, LVDd, LVDs, IVST, LVPWd, EF, E/A ratio in the basic treatment group had no significant changes on the 28th day after treatment. LVDd, LVDs, E/A ratio in the alprostadil treatment group on the 28th day after treatment were significantly reduced in comparison with the 3rd day after treatment (P <0.05) while IVST and LVPWd showed no significant changes. Alprostadil improves cardiac function after acute myocardial infarction in short term, but has no influence on preventing left ventricular remodeling.

Clinic significance of D-dimer in short-term prognosis of patients with acute heart failure

ZHANG Jialiang, GAO Rongrong, LI Xinli, WANG Hui

2016, 22(3):  376-380.  doi:10.3969/j.issn.1007-2861.2016.03.020

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This paper investigates the clinic significance of D-dimer in short-term prognosis of patients with acute heart failure (AHF). A total of 206 patients with AHF were enrolled and followed up for 3 months. Baseline level of complete blood count, complete biochemistry, D-dimer and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured at admission or in the following morning. Primary endpoints of the study were cardiovascular (CV) events, defined as cardiac death and/or readmission for AHF. D-dimer and NT-proBNP were significantly higher in the patients who had a CV events in a 90-day period (P < 0.001). The analysis results of the receiver operating characteristic (ROC) curves showed that the area under the curves (AUCs) of NT-proBNP, and D-dimer for predicting CV events within 90 days were 0.806 and 0.887. Kaplan-Meier survival curves for the 90-day CV events showed that patients with a D-dimer level > 1.1 mg/dL and NT-proBNP level > 2 262.0 pg/mL were at high risk (P < 0.001) for short-term outcomes of AHF. D-dimer can be used as a new biomarker to enhance the value in early predicting cardiovascular events of AHF when combined with NT-proBNP.