• 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.

• Korean Journal of Veterinary Research
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• v.63 no.4
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• pp.36.1-36.4
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• 2023

We discuss the case of a 5-month-old male British Shorthair cat referred to our hospital following the detection of a heart murmur during a routine vaccination appointment. Two-dimensional echocardiography revealed a 1.18 mm ventricular septal defect (VSD) located immediately below the aortic valve, without signs of secondary cardiac remodeling. Given the absence of cardiac dysfunction, no treatment was administered, and the cat was periodically monitored over the next 2 years. Echocardiography at 29 months of age revealed no signs of the VSD. Future studies are needed to increase the evidence base for spontaneous VSD closure in small animals.

• Korean Circulation Journal
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• v.53 no.6
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• pp.367-386
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• 2023

Ischemic heart disease remains the primary cause of morbidity and mortality worldwide. Despite significant advancements in pharmacological and revascularization techniques in the late 20th century, heart failure prevalence after myocardial infarction has gradually increased over the last 2 decades. After ischemic injury, pathological remodeling results in cardiomyocytes (CMs) loss and fibrosis, which leads to impaired heart function. Unfortunately, there are no clinical therapies to regenerate CMs to date, and the adult heart's limited turnover rate of CMs hinders its ability to self-regenerate. In this review, we present novel therapeutic strategies to regenerate injured myocardium, including (1) reconstruction of cardiac niche microenvironment, (2) recruitment of functional CMs by promoting their proliferation or differentiation, and (3) organizing 3-dimensional tissue construct beyond the CMs. Additionally, we highlight recent mechanistic insights that govern these strategies and identify current challenges in translating these approaches to human patients.

• Proceedings of the KAIS Fall Conference
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• 2011.12a
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• pp.170-173
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• 2011

Therapeutic hypothermia(TH) improves neurological outcomes and reduces mortality among survivors of out-of-hospital cardiac arrest. Animal and human studies have shown that TH results in improved salvage of the myocardium, reduced infarct size, reduced left ventricular remodeling and better long-term left ventricular function in settings of regional myocardial ischemia. This study is to investigate the effect of TH on post-resuscitation myocardial dysfunction and survival time after cardiac arrest and resuscitation in a rat model of myocardial infarction (MI). Thoracotomies were performed in 10 Male Sprague-Dawley rats weighing 450-550 g. MI was induced by ligation of the left anterior descending coronary artery (LAD). Ninety min after LAD ligation, ventricular fibrillation induction and subsequent cardiopulmonary resuscitation was performed before defibrillation attempts. Animals were randomized to two groups: a) Acute MI-Normothermia b) Acute MI-Hypothermia ($32^{\circ}C$ for 4 h). Myocardial functions, including cardiac output, left ventricular ejection fraction, and myocardial performance index were measured echocardiographically together with duration of survival. Ejection fraction, cardiac output and myocardial performance index were $54.74{\pm}9.16$, $89.00{\pm}8.89$, $1.30{\pm}0.09$ respectively and significantly better in the TH group than those of the normothermic group at the first 4 h after resuscitation($32.20{\pm}1.85$,$41.60{\pm}8.62$,$1.77{\pm}0.19$)(p=0.00). The survival time of the hypothermic group ($31.8{\pm}14.8$ h) was greater than that of the normothermic group($12.3{\pm}6.5$ h, p<0.05). This study suggested that TH attenuated post resuscitation myocardial dysfunction in acute MI and would be a potential strategy in post resuscitation care.

• Journal of Chest Surgery
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• v.39 no.3 s.260
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• pp.226-229
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• 2006

Recently, heart transplantation has been accepted as a standard treatment for infant and children with end-stage cardiomyopathy or complex congenital heart disease. Due to the shortage of donors, size-mismatched cardiac transplantation is common. After size-mismatched transplantation, there could be side-effects such as hypertension and hypertensive encephalopathy because of the big-heart. Donor heart is also known to do remodel as time goes by. This is a case report of a size-mismatched heart transplantation between 9-year-old boy and a 39-year-old female whose body weight is almost twice of him. In this case, classical postoperative hypertension and hypertensive encephalopathy developed but was successfully managed. The donor heart has remodeled to normal dimension during 3 years follow-up period.

• Clinical and Experimental Pediatrics
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• v.60 no.11
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• pp.365-372
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• 2017

Purpose: The mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis $factor-{\alpha}$, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot. Results: Ascites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group. Conclusion: ADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy.

• Endocrinology and Metabolism
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• v.33 no.4
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• pp.485-492
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• 2018

Background: Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA. Methods: Forty-two patients (mean age $48.8{\pm}10.9$ years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins. Results: The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was $8.9{\pm}0.3mg/dL$ (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ${\rho}=-0.424$, P=0.031). Moreover, multivariable regression analysis showed that the corrected calcium level was marginally associated with the LVEDD and corrected QT (QTc) interval (${\beta}=-0.366$, P=0.068 and ${\beta}=-0.252$, P=0.070, respectively). Conclusion: Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively.

• 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.

• Proceedings of the KSMRM Conference
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• 2003.10a
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• pp.45-45
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• 2003

To evaluate remodeling of infarcted myocardium with contrast-enhanced MRI (co-MRI) at true end-diastole (ED) MRI was performed with a Gyroscan Intera (1.5 Tesla, Philips, Netherlands) in 13 patients with acute subendocardial myocardial infarction. The First exam was done 0-15 days (mean 5.2days) after symptom onset and the second exam 28-88days (mean 49 days) after the first exam. Ce-MRI encompassing the entire left ventricle was performed with a multi-shot, turbo-field-echo, breath-hold sequence and a non-selective, inversion prepulse 10 minutes after the intravenous injection of Gd-DTPA at a dose of 0.2 mmol/kg body weight. To allow the long TD, ECG synchronization should use two RR-intervals for one acquisition of a segment of k-space by setting the heart rate to half that of the true heart rate. Trigger delay time (TD) was adjusted to the RR-interval for true end-diastolic imaging. The other typical parameters were TR=5.4ms, TE=1.6ms, voxel size=1.37${\times}$1.37${\times}$10mm, k-space data segmented into 8 segments with 32 lines of segment per two cycles over 16 cardiac circles. The thickness of hyperenhanced myocardium and epicardially nonenhanced myocardium were followed.

• Proceedings of the KSMRM Conference
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• 2003.10a
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• pp.92-92
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• 2003

To evaluate remodeling of infarcted myocardium with contrast-enhanced MRI (co-MRI) at true end-diastole (ED) MRI was performed with a Gyroscan Intera (1.5 Tesla, Philips, Netherlands) in 13 patients with acute subendocardial myocardial infarction. The First exam was done 0-15 days (mean 5.2days) after symptom onset and the second exam 28-88days (mean 49 days) after the first exam. Ce-MRI encompassing the entire left ventricle was peformed with a multi-shot, turbo-field-echo, breath-hold sequence and a non-selective, inversion prepulse 10 minutes after the intravenous injection of Gd-DTPA at a dose of 0.2 mmol/kg body weight. To allow the long TD, ECG synchronization should use two RR-intervals for one acquisition of a segment of k-space by setting the heart rate to half that of the true heart rate. Trigger delay time (TD) was adjusted to the RR-interval for true end-diastolic imaging. The other typical parameters were TR=5.4ms, TE=1.6ms, voxel size=1.37$\times$1.37$\times$10mm, k-space data segmented into 8 segments with 32 lines of segment per two cycles over 16 cardiac cycles. The thickness of hyperenhanced myocardium and epicardially nonenhanced myocardium were followed.