• BMB Reports
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• 제54권9호
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• pp.464-469
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• 2021

Cardiomyocyte differentiation occurs through complex and finely regulated processes including cardiac lineage commitment and maturation from pluripotent stem cells (PSCs). To gain some insight into the genome-wide characteristics of cardiac lineage commitment, we performed transcriptome analysis on both mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs) at specific stages of cardiomyocyte differentiation. Specifically, the gene expression profiles and the protein-protein interaction networks of the mESC-derived platelet-derived growth factor receptor-alpha (PDGFRα)⁺ cardiac lineage-committed cells (CLCs) and hiPSC-derived kinase insert domain receptor (KDR)⁺ and PDGFRα⁺ cardiac progenitor cells (CPCs) at cardiac lineage commitment were compared with those of mesodermal cells and differentiated cardiomyocytes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the genes significantly upregulated at cardiac lineage commitment were associated with responses to organic substances and external stimuli, extracellular and myocardial contractile components, receptor binding, gated channel activity, PI3K-AKT signaling, and cardiac hypertrophy and dilation pathways. Protein-protein interaction network analysis revealed that the expression levels of genes that regulate cardiac maturation, heart contraction, and calcium handling showed a consistent increase during cardiac differentiation; however, the expression levels of genes that regulate cell differentiation and multicellular organism development decreased at the cardiac maturation stage following lineage commitment. Additionally, we identified for the first time the protein-protein interaction network connecting cardiac development, the immune system, and metabolism during cardiac lineage commitment in both mESC-derived PDGFRα⁺ CLCs and hiPSC-derived KDR⁺PDGFRα⁺ CPCs. These findings shed light on the regulation of cardiac lineage commitment and the pathogenesis of cardiometabolic diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제26권5호
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• pp.357-365
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• 2022

Simultaneous myofibril and mitochondrial development is crucial for the cardiac differentiation of pluripotent stem cells (PSCs). Specifically, mitochondrial energy metabolism (MEM) development in cardiomyocytes is essential for the beating function. Although previous studies have reported that MEM is correlated with cardiac differentiation, the process and timing of MEM regulation for cardiac differentiation remain poorly understood. Here, we performed transcriptome analysis of cells at specific stages of cardiac differentiation from mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs). We selected MEM genes strongly upregulated at cardiac lineage commitment and in a time-dependent manner during cardiac maturation and identified the protein-protein interaction networks. Notably, MEM proteins were found to interact closely with cardiac maturation-related proteins rather than with cardiac lineage commitment-related proteins. Furthermore, MEM proteins were found to primarily interact with cardiac muscle contractile proteins rather than with cardiac transcription factors. We identified several candidate MEM regulatory genes involved in cardiac lineage commitment (Cck, Bdnf, Fabp4, Cebpα, and Cdkn2a in mESC-derived cells, and CCK and NOS3 in hiPSC-derived cells) and cardiac maturation (Ppargc1α, Pgam2, Cox6a2, and Fabp3 in mESC-derived cells, and PGAM2 and SLC25A4 in hiPSC-derived cells). Therefore, our findings show the importance of MEM in cardiac maturation.

• The Korean Journal of Physiology and Pharmacology
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• 제13권2호
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• pp.123-129
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• 2009

Aprotinin is used clinically in cardiopulmonary bypass surgery to reduce transfusion requirements and the inflammatory response. The mechanism of action for the anti-inflammatory effects of aprotinin is still unclear. We examined our hypothesis whether inhibitory effects of aprotinin on cytokine-induced inducible nitric oxide synthase (iNOS) expression (IL-$l\beta$ plus TNF-$\alpha$), reactive oxygen species (ROS) generation, and vascular smooth muscle cell (VSMC) proliferation were due to HO-l induction in rat VSMCs. Aprotinin induced HO-l protein expression in a dose-dependent manner, which was potentiated during inflammatory condition. Aprotinin reduced cytokine mixture (CM)-induced iNOS expression in a dose dependent manner. Furthermore, aprotinin reduced CM-induced ROS generation, cell proliferation, and phosphorylation of JNK but not of P38 and ERK1/2 kinases. Aprotinin effects were reversed by pre-treatment with the HO-l inhibitor, tin protoporphyrin IX (SnPPIX). HO-l is therefore closely involved in inflammatory-stimulated VSMC proliferation through the regulation of ROS generation and JNK phosphorylation. Our results suggest a new molecular basis for aprotinin anti-inflammatory properties.

• Journal of Chest Surgery
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• 제43권1호
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• pp.25-32
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• 2010

배경: 혈관질환 환자는 관상동맥질환 및 심장질환을 많이 동반함으로 인하여 혈관 수술 후 잠재되어 있는 심장질환이 악화 또는 유발될 수 있는 가능성이 있다. 이러한 심장질환을 확인하기 위한 검사중 비교적 간단하고 비침습적인 SPECT 촬영에 대한 효용성은 아직 논란이 되고 있다. 본 연구에서는 수술 전 SPECT를 촬영하고, 그 결과에 따른 검사 및 처치들이 혈관 수술 후 심장 합병증 발생에 미치는 임상적인 효과를 평가하고자 한다. 대상 및 방법: 2004년 4월부터 2007년 9월까지 3년 6개월간 본 병원에서 혈관 수술 전 아데노신 부하 Tc-99m 테트로포스민 SPECT를 촬영한 63명의 환자를 대상으로 하였다. 결과: SPECT 촬영 유소견의 심장 합병증 발생 예측에 대한 민감도와 특이도는 각각 41.2%와 52.2%로 비교적 낮게 나왔다. 그러나 비정상적인 SPECT 촬영결과를 보인 환자에게 관상동맥 조영술을 시행하고 관상동맥 병변에 대한 비정상 소견이 있을 때 관상동맥 중재적 시술 및 관상동맥 우회로술 등의 적극적인 처치를 한 경우 심장 합병증의 발생률이 낮은 경향을 보였다. 결론: SPECT 촬영은 혈관수술 후 심장 합병증 발생위험을 예측하기 위한 선별검사로서 효용성이 떨어진다.

• 대한핵의학회지
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• 제39권2호
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• pp.107-113
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• 2005

Pharmacologic stress testing for myocardial perfusion imaging is a widely used noninvasive method for the evaluation of known or suspected coronary artery disease. The use of exercise for cardiac stress has been practiced for over 60 years and clinicians are familial with its using. However, there are inevitabe situations in which exorcise stress is inappropriate. A large number of patients with cardiac problems are unable to exercise to their full potential due to comorbidity such as osteoarthritis, vascular disease and pulmonary disease and a standard exercise stress test for myocardial perfusion imaging is suboptimal means for assessment of coronary artery disease. This problem has led to the development of the pharmacologic stress test and to a great increase in its popularity. All of the currently used pharmacologic agents have well-documented diagnostic value. This review deals the physiological actions, clinical protocols, safety, nuclear imaging applications of currently available stress agents and future development of new vasodilating agents.

• 대한핵의학회지
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• 제39권2호
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• pp.69-74
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• 2005

Ever since it was first introduced as a method of scintigraphically measuring regional myocardial perfusion, myocardial perfusion study has been widely used in patients diagnosed or suspected with coronary artery diseases, and continuously improved upon. In addition to the technological enhancement of nuclear medicine equipments, the innovation of radiopharmaceuticals used in the cardiac exams were important contributors to such improvement. Besides the cardiac perfusion studies, new radiopharmaceuticals that visualize fat metabolism or receptors of the sympathetic nervous system have successfully been applied to clinical practice. More information can be collected before diagnosing coronary vascular disease, evaluating the patient's condition, or assessing therapeutic effects. In this review article, the clinical efficacy and characteristics of radiopharmaceutical products tailored for cardiac SPECT that are commonly used in Korea currently, plus the ones not being used yet but have proven value are briefly described.

• Journal of Chest Surgery
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• 제23권4호
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• pp.659-666
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• 1990

We evaluated 68 patients with mitral valve disease who underwent mitral valve replacement from April, 1986, to December, 1988. Among them 20 patients showed increased systolic pulmonary arterial pressure greater than 60 mmHg and postoperative hemodynamic data were obtained in 19 patients average 13 months after mitral valve replacement. The results were as followings. 1. Average pulmonary systolic pressure decreased from 84.8$\pm$4.5 preoperatively to 33. 0$\pm$1.9mmHg postoperatively[P<0.001]. 2. Average pulmonary vascular resistance index decreased from 1425$\pm$148 preoperatively to 287+35.8 dyne * sec * cm2 * m postoperatively[P<0.001]. 3. Average cardiac index rose from 1.927$\pm$0.169 preoperatively to 2.625$\pm$0.159 L/min/m2 postoperatively [P <0.005]. This study shows that pulmonary hypertension and the increased pulmonary vascular resistance index due to mitral valve disease can regress significantly after mitral valve replacement.

• Integrative Medicine Research
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• 제3권4호
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• pp.204-210
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• 2014

The aim of this review was to understand the effects of ${\beta}$-adrenergic stimulation on oxidative stress, structural remodeling, and functional alterations in the heart and cerebral artery. Diverse stimuli activate the sympathetic nervous system, leading to increased levels of catecholamines. Long-term overstimulation of the ${\beta}$-adrenergic receptor (${\beta}AR$) in response to catecholamines causes cardiovascular diseases, including cardiac hypertrophy, stroke, coronary artery disease, and heartfailure. Although catecholamines have identical sites of action in the heart and cerebral artery, the structural and functional modifications differentially activate intracellular signaling cascades. ${\beta}AR$-stimulation can increase oxidative stress in the heart and cerebral artery, but has also been shown to induce different cytoskeletal and functional modifications by modulating various components of the ${\beta}AR$ signal transduction pathways. Stimulation of ${\beta}AR$ leads to cardiac dysfunction due to an overload of intracellular $Ca^{2+}$ in cardiomyocytes. However, this stimulation induces vascular dysfunction through disruption of actin cytoskeleton in vascular smooth muscle cells. Many studies have shown that excessive concentrations of catecholamines during stressful conditions can produce coronary spasms or arrhythmias by inducing $Ca^{2+}$-handling abnormalities and impairing energy production in mitochondria, In this article, we highlight the different fates caused by excessive oxidative stress and disruptions in the cytoskeletal proteome network in the heart and the cerebral artery in responsed to prolonged ${\beta}AR$-stimulation.

• Nuclear Medicine and Molecular Imaging
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• 제40권3호
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• pp.155-162
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• 2006

목적 : 당뇨병 환자에서는 관동맥질환의 이환율이 높고 무통성 심근경색과 심근허혈의 빈도가 높아 조기발견이 어렵다. 또한 진단될 당시에 이미 심각한 수준의 관동맥질환을 가지고 있는 경우가 많다. 본 연구에서는 Tc-99m MIBI 심근관류 SPECT을 이용하여 당뇨병 환자에서 관동맥질환의 빈도를 평가하고 전통적인 심장위험 인자들을 포함한 여러 임상시험인자들 중에서 진단이 필요한 고위험군 환자들을 예측할 수 있는 인자들을 알아보고자 하였다. 대상 및 방법 : 2000년 1월부터 2004년 7월 사이에 심근관류 SPECT 검사가 의뢰된 203명의 당뇨병환자(남 64명, 평균연령 $64.9{\pm}9.0$세)를 대상으로 하였다. 심장사망 및 비치명적 심근경색을 중증심장사건으로 정의하였고, 검사 후 60일 이후에 경피적 관동맥성형술이나 관동맥 우회수술을 시행한 정도의 심근허혈의 악화를 경증심장사건으로 정의하였다. 환자들은 운동 부하 (n=6) 혹은 adenosine (n=197) 부하 Tc-99m MIBI 심근관류 SPECT을 시행하였다. 이중검출기(ADAC, USA) 혹은 삼중검출기 감마카메라(PRISM 3000, Picker, USA)를 이용하여 SPECT 영상을 획득하였다. 결과: 심근관류 SPECT 결과 관동맥질환이 진단된 환자들은 58명으로 전체 대상 환자 중 28.6%였다. 총 11건의 중증심장사건, 즉 비치명적 심근경색이 발생하였고 10건의 경증심장사건이 관찰되었다. 전체 대상 당뇨병 환자들의 연간 심장사건 발생률은 1.1%였다. 임상인자들의 단변량 분석 결과, 전형적인 협심증상, 말초혈관병증, 다발성 말초신경병증, 그리고 안정시 심전도상 이상이 심장사건의 발생과 유의한 관련성이 있는 것으로 나타났다. 다변량 분석에서는 전형적인 협심증상, 말초혈관병증, 그리고 안정시 심전도상 이상만이 비치명적 심근경색 발생에 대한 독립적인 예측인자인 것으로 나타났다. SPECT 검사상 관류 이상 소견이 있었던 환자들에게서 중증 심장사건이 일어나는 빈도도 높았으나 심장사건의 독립적인 예측인자는 아니었다. 결론: 당뇨병 환자에서 관동맥질환의 빈도는 정상건강인들에 비해 높았다. 특히 남자, 20년 이상의 긴 당뇨병 이환 기간, 말초혈관병증, 다발성 말초신경병증, 또는 안정시 심전도 이상을 가지고 있는 환자들에서 유의하게 더 높은 빈도로 관동맥질환이 나타남을 알 수 있었다. 그리고 전형적인 협심증상, 말초혈관병증, 다발성 말초신경병증, 안정시 심전도 이상이 있는 환자들에서 이후 중증 심장사건이 발생할 위험이 더 큰 것으로 나타났다.

• 대한족부족관절학회지
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• 제4권2호
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• pp.83-86
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• 2000

A vascular necrosis of the talus has frequently been reported following trauma because talus has no muscle insertions, sixty percent of the surface of the talus is covered by hyaline cartilage, takes only a small area for entrance of a blood supply. Osteonecrosis is also associated with a variety of nontraumatic disorders. There are many indications for steroid usage, patient with rheumatoid arthritis, systemic lupus erythematosus, chronic obstructive pulmonary disease, and status- post renal or cardiac transplantation may be on long- term steroid usage, osteonecrosis may develop. A vascular necrosis of the talus secondary to chronic steroid usage is an unusual case. Delay in detection of osteonecrosis may lead to fragmentation and collapse of the talar body. When pain on range of motion is present and conservative treatment have been exhausted, surgical treatment is indicated, that is, fusion of the ankle joint. However it is important that conservative treatment may prevent its various sequelae with early diagnosis because steroid - treated patients have a more operative risk and increased risk for postoperative infection. We report a rare case of corticosteroid induced avascular necrosis of talus after cardiac transplantation.