• Molecules and Cells
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• v.37 no.4
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• pp.330-336
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• 2014

Thymosin beta4 (TB4) has multiple functions in cellular response in processes as diverse as embryonic organ development and the pathogeneses of disease, especially those associated with cardiac coronary vessels. However, the specific roles played by TB4 during heart valve development in vertebrates are largely unknown. Here, we identified a novel function of TB4 in endothelial-mesenchymal transformation (EMT) in cardiac valve endocardial cushions in zebrafish. The expressions of thymosin family members in developing zebrafish embryos were determined by whole mount in situ hybridization. Of the thymosin family members only zTB4 was expressed in the developing heart region. Cardiac valve development at 48 h post fertilization was defected in zebrafish TB4 (zTB4) morpholino-injected embryos (morphants). In zTB4 morphants, abnormal linear heart tube development was observed. The expressions of bone morphogenetic protein (BMP) 4, notch1b, and hyaluronic acid synthase (HAS) 2 genes were also markedly reduced in atrio-ventricular canal (AVC). Endocardial cells in the AVC region were stained with anti-Zn5 antibody reactive against Dm-grasp (an EMT marker) to observe EMT in developing cardiac valves in zTB4 morphants. EMT marker expression in valve endothelial cells was confirmed after transfection with TB4 siRNA in the presence of transforming growth factor ${\beta}$ ($TGF{\beta}$) by RT-PCR and immunofluorescent assay. Zn5-positive endocardial AVC cells were not observed in zTB4 morphants, and knockdown of TB4 suppressed TGF-${\beta}$-induced EMT in ovine valve endothelial cells. Taken together, our results demonstrate that TB4 plays a pivotal role in cardiac valve formation by increasing EMT.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.477-485
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• 2016

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

• Molecules and Cells
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• v.37 no.1
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• pp.81-87
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• 2014

Chronic pressure-overload cardiac hypertrophy is associated with an increased risk of morbidity/mortality, largely due to maladaptive remodeling and dilatation that progresses to dilated cardiomyopathy. Alternative splicing is an important biological mechanism that generates proteomic complexity and diversity. The recent development of next-generation RNA sequencing has improved our understanding of the qualitative signatures associated with alternative splicing in various biological conditions. However, the role of alternative splicing in cardiac hypertrophy is yet unknown. The present study employed RNA-Seq and a bioinformatic approach to detect the RNA splicing regulatory elements involved in alternative splicing during pressure-overload cardiac hypertrophy. We found GC-rich exonic motifs that regulate intron retention in 5' UTRs and AT-rich exonic motifs that are involved in exclusion of the AT-rich elements that cause mRNA instability in 3' UTRs. We also identified motifs in the intronic regions involved in exon exclusion and inclusion, which predicted splicing factors that bind to these motifs. We found, through Western blotting, that the expression levels of three splicing factors, ESRP1, PTB and SF2/ASF, were significantly altered during cardiac hypertrophy. Collectively, the present results suggest that chronic pressure-overload hypertrophy is closely associated with distinct alternative splicing due to altered expression of splicing factors.

• The Korean Society of Law and Medicine
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• v.19 no.2
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• pp.209-233
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• 2018

The purpose of this study was to ascertain whether or not to recover the spontaneous circulation of patients with cardiac arrest before arrival in the emergency room for 5 years (2012 to 2016), and try to investigate the factors affecting this. In this research, we used the "raw material for acute cardiac arrest survey" conducted in "Disease management headquarters" from 2012 to 2016 for the whole country of our country as the main material. In this study, 136,212 cardiac arrest patients were analyzed in the study data of the cardiac arrest in the country during the 5 years from 2012 to 2016. We performed a Chi-square analysis to analyze the recovery of spontaneous circulation before arrival in the emergency room according to general characteristics, social·demographic characteristics, and developmental characteristics. and We performed a Binary logistic regression analysis to determine the factors affecting the recovery of spontaneous circulation. The analysis results of this study show that whether CPR sustained transport before endoplasmic reticulum arrival, whether to witness an acute cardiac arrest before arrival in the emergency room, the type of general cardiopulmonary resuscitation, the location of acute cardiac arrest, the acute heart Causes of stoppage cause factor of whether spontaneous circulation recovery recovers before arrival of the endoplasmic reticulum(P<0.001, P<0.01). Therefore, it is necessary to strengthen systematic government health policy implementation and dissemination and health education focusing on factors that affect recovery of spontaneous circulation of cardiac arrest patients.

• BMB Reports
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• v.52 no.10
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• pp.595-600
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• 2019

Cardiac fibrosis is a common feature in chronic hypertension patients with advanced heart failure, and endothelial-to-mesenchymal transition (EndMT) is known to promote Angiotensin II (Ang II)-mediated cardiac fibrosis. Previous studies have suggested a potential role for the transcription factor, ETS-1, in Ang II-mediated cardiac remodeling, however the mechanism are not well defined. In this study, we found that mice with endothelial Ets-1 deletion showed reduced cardiac fibrosis and hypertrophy following Ang II infusion. The reduced cardiac fibrosis was accompanied by decreased expression of fibrotic matrix genes, reduced EndMT with decreased Snail, Slug, Twist, and ZEB1 expression, as well as reduced cardiac hypertrophy and expression of hypertrophy-associated genes was observed. In vitro studies using cultured H5V cells further confirmed that ETS-1 knockdown inhibited $TGF-{\beta}1$-induced EndMT. This study revealed that deletion of endothelial Ets-1 attenuated Ang II-induced cardiac fibrosis via inhibition of EndMT, indicating an important ETS-1 function in mediating EndMT. Inhibition of ETS-1 could be a potential therapeutic strategy for treatment of heart failure secondary to chronic hypertension.

• The Korean Journal of Emergency Medical Services
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• v.9 no.2
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• pp.111-128
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• 2005

Background: Cardiac arrest is one of the most critical diseases which can likely lead to severe cerebral disability or brain death when the cases can not recover their circulation within 10 minutes. Saving out-of-hospital cardiac arrest cases is a recent concern in Korea. Resuscitation has become an important multidisciplinary branch of medicine, demanding a spectrum of skills and attracting a plethora of specialities and organizations. The best survival can be achieved if all the following links have been optimized : rapid access, and early CPR, defibrillation and ACLS, Since the "Utstein Style" was advocated in 1991, many reports about out-of-hospital cardiac arrest have been published based on this guideline. These differences prevent valid inter-hospital and international comparisons. However, it is not known how effective resuscitation has become to the patients. In other words, there are no guidelines for reviewing, reporting, and conducting research on resuscitation in Korea. This dissertation aims to provide the basic data for a unified reporting guideline of resuscitation in Korea and evaluating the out-of-hospital factors associated with survival discharge of out-of-hospital cardiac arrest. Methods: As for this study, uses the collected data about Out-of-hospital cardiac arrests at 4 area, from January, 2005 to April. 2005. With a retrospective study, 174 cases were analyzed. The data was recorded based on the Out-of-Hospital Utstein Style. Results: Resuscitation was performed on 174 out-of-hospital cardiac arrest cases at the 4 area 14 patients(8.1%) recovered their spontaneous circulation. Overall, the ROSC of the out-of-hospital cardiac arrest patients was 8.1%, which was poorer than that of western countries. Gender distribution was 50 females(28.7%) and 124 males(71.3%), approximately twice as many males as females. ROSC of witnessed arrests was found out to be 97.7%. The ratio of the witnessed arrest groups showed higher results than that of unwitnessed arrest groups in the above-examined cases. Cardiac etiology consisted of cardiac(33.5%), non-cardiac(45.7%), trauma(20.1%), and unknown(6.0%). Cardiac was the best performance. Initial rhythm showed Ventricular Tachycardia/pulseless Ventricular Fibrillation in 8 patients(6.0%), asystole in 100(75.2%) and unknown in 25(18.8%). The results of the Ventricular Tachycardia/pulseless Ventricular Fibrillation showed higher results than the others cases, The proportion of the cardiogenic cause was 33.5%, which was only half of western countries. Ventricular Tachycardia/pulseless Ventricular Fibrillation is relatively rare. These differences were due to the prevalent pattern of Out-of-hospital cardiac arrest as well as prematurity of the EMSS. Bystander CPR was practiced on 13 patients(7.52%). ROSC was shown in 46.2% cases. CPR by EMT was carried out on 167 cases(96.5%). ACLS by EMf was rare. From collapse, 4 cases(2.6%) arrived to ED within 6 minutes. 13 (8.6%) within 10 minutes, and 49(32.5%) over 31 minutes. The sooner the patients arrived, the greater the ratio of ROSC and discharged alive became, and the same with collapse time to ROSC. As the results of the logistic regression analysis, ROSC was found out to be highly influenced by the time of ED arrival from collapse and Ventricular Tachycardia/pulseless Ventricular Fibrillation. Therefore, the ratio of ROSC depends on not any single factor but various intervention factors. Conclusion: This dissertation presents the following suggestions and directions of the study hereafter. First, the first step for a chain of survival should be taken to activate EMSS early with a phone as soon as cardiac arrests are witnessed. Second, it is keenly needed that emergency medical technicians should be increased through emergency education for living. Third, it is necessary to establish the emergency transportation system. Fourth, most of the Koreans have little understanding of EMT and the present operation systems have many problems, which should be fundamentally changed. Fifth, it is required to have an active medical control over Out-of-hospital CPR, And proper psychological supports should be given not only to patients themselves and their family but also individuals who are engaged in emergency situation. Finally, through studies hereafter on nationwide, comprehensive, and standard forms, it is needed to examine into the biological figures of human body, causes and trends of cardiac arrests, and then, to enhance the survival rate of Out-of-hospital cardiac arrests. Korean guidelines for Cardiopulmonary resuscitation need to be made.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.206-212
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• 2015

Background: Ginseng total saponin (GTS) contains various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The aim of this study was to study the effects of GTS on cardiac injury after global ischemia and reperfusion (I/R) in isolated guinea pig hearts. Methods: Animals were subjected to normothermic ischemia for 60 minutes, followed by 120 minutes of reperfusion. GTS significantly increased aortic flow, coronary flow, and cardiac output. Moreover, GTS significantly increased left ventricular systolic pressure and the maximal rate of contraction ($+dP/dt_{max}$) and relaxation ($-dP/dt_{max}$). In addition, GTS has been shown to ameliorate electrocardiographic changes such as the QRS complex, QT interval, and RR interval. Results: GTS significantly suppressed the biochemical parameters (i.e., lactate dehydrogenase, creatine kinase-MB fraction, and cardiac troponin I levels) and normalized the oxidative stress markers (i.e., malondialdehyde, glutathione, and nitrite). In addition, GTS also markedly inhibits the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, and nuclear factor-${\kappa}B$, and improves the expression of IL-10 in cardiac tissue. Conclusion: These data indicate that GTS mitigates myocardial damage by modulating the biochemical and oxidative stress related to cardiac I/R injury.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.153-159
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• 2009

We investigated whether deficiency of inducible nitric oxide synthase (iNOS) could prevent isoproterenol-induced cardiac hypertrophy in iNOS knockout (KO) mice. Isoproterenol was continuously infused subcutaneously (15 mg/kg/day) using an osmotic minipump. Isoproterenol reduced body weight and fat mass in both iNOS KO and wild-type mice compared with saline-infused wild-type mice. Isoproterenol increased the heart weight in both iNOS KO and wild-type mice but there was no difference between iNOS KO and wild-type mice. Posterior wall thickness of left ventricle showed the same tendency with heart weight. Protein level of iNOS in the left ventricle was increased in isoproterenol-infused wild-type mice. The gene expression of interleukin-6 (IL-6) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in isoproterenol-infused wild-type was measured at 2, 4, 24, and 48-hour and isoproterenol increased both IL-6 (2, 4, 24, and 48-hour) and TGF-${\beta}$ (4 and 24-hour). Isoproterenol infusion for 7 days increased the mRNA level of IL-6 and TGF-${\beta}$ in iNOS KO mice, whereas the gene expression in wild-type mice was not increased. Phosphorylated form of extracellular signal-regulated kinases (pERK) was also increased by isoproterenol at 2 and 4-hour but was not increased at 7 days after infusion in wild-type mice. However, the increased pERK level in iNOS KO mice was maintained even at 7 days after isoproterenol infusion. These results suggest that deficiency of iNOS does not prevent isoproterenol-induced cardiac hypertrophy and may have potentially harmful effects on cardiac hypertrophy.

• Biomedical Science Letters
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• v.11 no.3
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• pp.397-405
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• 2005

Noise may cause damage of the auditory system, hypertension, and cardiovascular disease. However, we haven't the data enough to be available for understanding various effects of noise on the human body. The current study was prospectively designed to investigate the changes of the cardiac factors and cerebral hemodynamics following a transient exposure to noise in young people. 80 subjects (mean aged $23.45\pm2.40$ years) participated in this experiment and were exposed to excavator-noise with 90 decibels for 15 minutes using ear-phone. Cardiac factors such as heart rate (HR), blood pressure (BP) and heart rate-systolic pressure product (RPP), and cerebral hemodynamics such as mean blood flow velocities (Vm), pulsatility indexes (PI), resistance indexes (RI) and mean blood flow velocities at breathing-hold (Vh) in the middle (MCA), anterior (ACA) and posterior cerebral arteries (PCA) were measured before (baseline) and during the noise-exposure. Although there were individual differences in above mentioned parameters, HR, systolic and diastolic BP, RPP, MCA-Vm, MCA-PI, MCA-RI, ACA-Vm, ACA-PI, ACA-RI, PCA-Vm, PCA-PI, and PCA-RI during the noise-exposure decreased compared with the baselines (P<0.05 or P<0.01), The findings of the present study suggest that a transient exposure to excavator-noise at rest causes changes in the cardiac factors and cerebral hemodynamics with individual differences. Further studies need to be carried out for clarifying the effects of longer exposure and combined mental activity with noise exposure.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.19-24
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• 2016

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. The exploration of new biomarkers with high sensitivity and specificity for early diagnosis of AMI therefore becomes one of the primary task. In the current study, we aim to detect whether there is any heart specific long noncoding RNA (lncRNA) releasing into the circulation during AMI, and explore its function in the neonatal rat cardiac myocytes injury induced by $H_2O_2$. Our results revealed that the cardiac-specific lncRNA MHRT (Myosin Heavy Chain Associated RNA Transcripts) was significantly elevated in the blood from AMI patients compared with the healthy control ($^*p<0.05$). Using an in vitro neonatal rat cardiac myocytes injury model, we demonstrated that lncRNA MHRT was upregulated in the cardiac myocytes after treatment with hydrogen peroxide ($H_2O_2$) via real-time RT-PCR (qRT-PCR). Furthermore, we knockdowned the MHRT gene by siRNA to confirm its roles in the $H_2O_2$-induced cardiac cell apoptosis, and found that knockdown of MHRT led to significant more apoptotic cells than the non-target control ($^{**}p<0.01$), indicating that the lncRNA MHRT is a protective factor for cardiomyocyte and the plasma concentration of MHRT may serve as a biomarker for myocardial infarction diagnosis in humans AMI.