• Molecules and Cells
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• 제43권4호
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• pp.408-418
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• 2020

The sinus node (SN) is located at the apex of the cardiac conduction system, and SN dysfunction (SND)-characterized by electrical remodeling-is generally attributed to idiopathic fibrosis or ischemic injuries in the SN. SND is associated with increased risk of cardiovascular disorders, including syncope, heart failure, and atrial arrhythmias, particularly atrial fibrillation. One of the histological SND hallmarks is degenerative atrial remodeling that is associated with conduction abnormalities and increased right atrial refractoriness. Although SND is frequently accompanied by increased fibrosis in the right atrium (RA), its molecular basis still remains elusive. Therefore, we investigated whether SND can induce significant molecular changes that account for the structural remodeling of RA. Towards this, we employed a rabbit model of experimental SND, and then compared the genome-wide RNA expression profiles in RA between SND-induced rabbits and sham-operated controls to identify the differentially expressed transcripts. The accompanying gene enrichment analysis revealed extensive pro-fibrotic changes within 7 days after the SN ablation, including activation of transforming growth factor-β (TGF-β) signaling and alterations in the levels of extracellular matrix components and their regulators. Importantly, our findings suggest that periostin, a matricellular factor that regulates the development of cardiac tissue, might play a key role in mediating TGF-β-signaling-induced aberrant atrial remodeling. In conclusion, the present study provides valuable information regarding the molecular signatures underlying SND-induced atrial remodeling, and indicates that periostin can be potentially used in the diagnosis of fibroproliferative cardiac dysfunctions.

• Tuberculosis and Respiratory Diseases
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• 제82권2호
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• pp.102-117
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• 2019

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.

• BMB Reports
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• 제53권11호
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• pp.600-604
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• 2020

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.

• 대한수의학회지
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• 제44권1호
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• pp.125-129
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• 2004

A 2-year-old, female, American cocker spaniel dog presented for a 1-year history of severe ascites, exercise intolerance, tachypnea. At that time, she was in an emergency state. First, the dog was stabilized with oxygen therapy. A diagnosis of cardiac problem was made from history, auscultation, radiograph, ECG, and echocardiography. Jugular pulsation was palpated and a harsh, systolic murmur of tricuspid regurgitation was prominent at the right cardiac apex. Tricuspid valve dysplasia (TVD) was confirmed with echocardiography, accompanying enormous myocardial hypertrophy. The clinical signs had been improved for 8 months with careful therapy and periodic abdominocentesis, and ascites was well controlled. The situation, however, became worse quickly in a week because the client did not follow our management schedule. Finally, she died due to dyspnea and shock. After the spontaneous death, necropsy and histopathological examination were performed and when we opened the thorax, a significantly large heart was observed. On histopathological findings, grossly myocardium appeared pale initially, then progressed to yellow and white. Microscopically, there was an extensive hemorrhage along with loss of myocardial striations. Interstitial fibrosis and various degenerative alterations in myocytes were also present.

• Journal of Chest Surgery
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• 제39권11호
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• pp.850-853
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• 2006

일반적으로 활로씨 4증에서의 심실 중격 결손은 보통 대동맥 판막륜의 크기와 같거나 크고 제한적이지 않다. 또한 심실 중격 결손을 통한 단락의 방향은 양방향성 또는 우-좌 단락인 경우가 대부분이다. 이러한 활로씨 4증에서 섬유성 조직의 성장으로 인한 제한적 심실 중격 결손은 드물게 보고되고 있다. 저자들은 활로씨 4증에서의 섬유성 조직으로 인한 제한적 심실 중격 결손과 좌심실 유출로 협착을 보였던 환아에 대한 완전 교정술 치험 1예를 문헌 고찰과 함께 보고한다.

• 대한유전성대사질환학회지
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• 제18권3호
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• pp.87-94
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• 2018

선천성 염소성 설사를 가진 환아에서 국소 분절 사구체경화증이 발생하여 말기 신장병으로 발전한 사례를 보고 하고자 한다. 20세 여자 환자로, 본원에서 출생 전 산전진단에서 양수과다 및 초음파 소견으로 선천성 염소성 설사가 의심되었으며, 출생 직후 확진 되어 신생아기 때부터 KCl 보충을 통하여 증상 조절을 시작하였다. 환아는 이후 특별한 건강의 문제가 없었으나 12세에 단백뇨가 관찰되었고, 16세때 본원에서 국소분절 사구체경과증 과 2기 만성신장병 진단을 받았다. 이후 보존적 치료를 하였으며, 지속적인 단백뇨에 대한 재 평가를 위하여 입원하게 되었다. 입원 후 확인된 검사에서 사구체여과율(GFR)은 4기 신장병으로 악화되어 있었으며 신생검에서도 국소분절 사구체신염으로 인한 만성 신장병이 재 확인 되었다. 환아 및 가족을 대상으로 시행한 유전자 검사(diagnostic exome sequencing)에서는 SLC26A3 유전자의(c.2063-1G>T) 동형 접합체 변이가 각각 부모에서 전달된 것을 확인하였다. 선천성 염소성 설사 환자는 적절한 전해질 보충에도 불구하고 신기능 손상이 되기 쉬운 경향이 있으며, 따라서 조기 진단 및 충분한 전해질 보충이 이루어지는 경우에서도 환자의 신장 기능에 대한 정기적 관찰 및 적절한 보조 치료가 필요할 것으로 사료된다.

• Journal of Ginseng Research
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• 제44권4호
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• pp.664-671
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• 2020

Background: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods: We treated H9c2 cells with hydrogen peroxide (H₂O₂) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)-induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H₂O₂-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H₂O₂-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress-related cardiac diseases.

• Journal of Chest Surgery
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• 제35권1호
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• pp.1-10
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• 2002

배경 : 관상동맥 결찰법에 의한 만성 심부전 모델은 실험 사망률이 비교적 높음에도 불구하고 임상적 연관성때문에 지속적인 연구 대상이 된다. 특히 대동물에서 만성 심부전 모델 확립은 소동물에서는 검증할 수 없는 기계 또는 생물학적 순환보조시스템의 연구분석에 대단히 유용하게 사용될 수 있다 이런 관점에서 본연구는 양에서 homonymous artery(사람의 좌전하행지에 해당)와 diagonal branch를 순차적으로 결찰 하는 방법으로 신뢰성 있는 만성 심부전 모델을 확립하고자 하였다. ·재료 및 방법: 모두 9마리의 Corridale 양을 사용하였다. 2마리 양에서 homonymous artery 와 diagonal branch를 동시에 결찰 하였고 7마리에서는 homonymous artery와 diagonal branch를 1시간 간격으로 결찰 하였다. 좌전 개흉술로 심장을 노출시킨 후 심첨부에서 기저부까지의 거리를 기준으로 하여 심첨부에서 40% 위치에서 homonymous artery를 결찰 하였다. diagonal branch는 homonymous artery와 동일한 위치에서 결찰 하였다. 관상동맥 결찰 전, homonymous artery 결찰 후,그리고 diagonal branch 추가 결찰 후 각각 동맥압, 심전도, 그리고 thermodilution catheter로 중심정맥압, 폐동맥압, 폐동맥쐐기압, 심박출량을 측정하였다. 같은 시점에 초음파 검사를 통해 좌심실 이완말기 크기, 좌심실수축말기 크기, 좌심실 구혈률, 좌심실 벽두께, 좌심실 구획단축률과 좌심실 벽운동을 분석하였다. 실험 동물은 2개월 또는 3개월 사육한 뒤 같은 분석 과정을 거친 후 희생시켰다. 실험양의 심장은 적출하여 병리조직학적 검사를 하였다. 결과 Homonymous artery 와 diagonal branch를 동시에 결찰 한 2마리는 결찰 직후 모두 사망하였다. 반면 homonymous artery 와 diagonal branch를 순차적으로 결찰 한 7마리는 모두 생존하였는데 이중 5마리는 2개월 그리고 2마리는 3개월 사육후 심장을 적출하였다. 결찰 2~3개월 후 양에서 중심정맥압, 폐동맥압, 폐동맥쐐기압, 좌심실 이완말기 및 수축말기 크기의 유의한 증가가 관찰되었다(p<0.05) 반면 homonymous artery 결찰 직후에는 동맥압의 유의한 감소(p<0.05)가 diagonal branch의 추가 결찰 후에는 동맥압, 심박출량의 감소 및 폐동맥쐐기압의 유의한 증가가 관찰되었다(p<0.05). 좌심실 벽운동은 결찰 직후부터 다양한 정도의 anteroseptal akinesia또는 dyskinesia가 관찰되었다. 적출 심장의 병리 분석 결과 주위와 잘 구별되는 섬유화 경색 부위가 관찰되었다. 결론: 양에서 homonymous artery와 diagonal branch를 순차적으로 결찰하는 방법으로 신뢰성 있는 만성 심부전 모델을 확립할 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.305-314
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• 2016

Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating inflammation and fibrosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 ($10{\mu}mol/L$) treatment as experimental models. Addition of NecroX-5 significantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 ($TGF{\beta}1$) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, significantly increased production of tumor necrosis factor alpha ($TNF{\alpha}$), $TGF{\beta}1$, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of $TNF{\alpha}$, $TGF{\beta}1$, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the $TNF{\alpha}/Dcn/TGF{\beta}1/Smad2$ pathway.

• Investigative Magnetic Resonance Imaging
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• 제15권1호
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• pp.1-10
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• 2011

색소성 융모결절성 윤활막염, 윤활막 연골종증, 장기간의 류마티스 관절염, 혈우병성 관절병증, 만성 결절성 통풍, 아밀로이드성 관절병증, 결핵성 관절염, 그리고 혈관종 등은 T2 강조 MR 영상에서 저신호강도를 보인다. 혈철소, 요산, 아밀로이드의 윤활막 침착, 증식된 윤활막의 섬유화, 치즈괴사 등이 T2 저신호강도의 병리적 원인으로 알려져 있다. T2 강조영상에서 저신호강도를 보이는 윤활막 질환의 빈도는 낮으므로 이에 대한 숙지는 질환의 정확한 진단에 도움을 줄 것이다.