• International Journal of Contents
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• 제8권4호
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• pp.64-69
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• 2012

The heart is a major dose-limiting organ for radiotherapy of cancer in the thoracic region. The purpose of this study was to examine the protective effect of tranilast on the radiation-induced heart fibrosis model using the C57BL/6 murine strain. A significant reduction in the expression of TGF-${\beta}1$, collagen type I and collagen type III was observed in the radiation plus tranilast group. The authors also suggest the use of tranilast in a clinical trial for the prevention of radiation-induced heart fibrosis.

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.533-543
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• 2021

Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.

• 대한약침학회지
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• 제21권4호
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• pp.284-293
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• 2018

Objectives: Thymoquinone (TQ) is one of the active ingredients of herbal plants such as Nigella sativa L. (NS) which has beneficial effects on the body. The beneficial effects of TQ on the cardiovascular system have reported. This study aimed to investigate the effect of TQ on cardiac fibrosis and permeability, serum and tissue concentration of inflammatory markers and oxidative stress status in chronic lipopolysaccharide exposure in male rats. Methods: Seventy male Wistar rats were randomly divided into five groups as follows: (1) control; (2) LPS (1 mg/kg/day); (3-5) LPS + TQ with three doses of 2, 5 and 10 mg/kg (n=14 in each group). After 3 weeks, serum and cardiac levels of $IL-1{\beta}$, $TNF-{\alpha}$ and nitric oxide (NO) metabolites, and cardiac levels of malondialdehyde (MDA), total thiol groups, catalase (CAT) and superoxide dismutase (SOD) activities, permeability of heart tissue (evaluated by Evans blue dye method) and myocardial fibrosis were determined, histologically. Results: LPS administration induced myocardial and perivascular fibrosis and increased cardiac oxidative stress (MDA), inflammatory markers and heart permeability, while, reduced anti-oxidative enzymes (SOD and CAT) and the total thiol group. Administration of TQ significantly attenuated these observations. Conclusion: TQ improved myocardial and perivascular fibrosis through suppression of chronic inflammation and improving oxidative stress status and can be considered for attenuation of cardiac fibrosis in conditions with chronic low-grade inflammation.

• The Korean Journal of Physiology and Pharmacology
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• 제25권2호
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• pp.131-137
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• 2021

Aging is the process spontaneously occurred in living organisms. Cardiac fibrosis is a pathophysiological process of cardiac aging. Mangiferin is a well-known C-glucoside xanthone in mango leaves with lots of beneficial properties. In this study, rat model of cardiac fibrosis was induced by injected with 150 mg/kg/d D-galactose for 8 weeks. The age-related cardiac decline was estimated by detecting the relative weight of heart, the serum levels of cardiac injury indicators and the expression of hypertrophic biomakers. Cardiac oxidative stress and local inflammation were measured by detecting the levels of malondialdehyde, enzymatic antioxidant status and proinflammatory cytokines. Cardiac fibrosis was evaluated by observing collagen deposition via masson and sirius red staining, as well as by examining the expression of extracellular matrix proteins via Western blot analysis. The cardiac activity of profibrotic TGF-β1/p38/MK2 signaling pathway was assessed by measuring the expression of TGF-β1 and the phosphorylation levels of p38 and MK2. It was observed that mangiferin ameliorated D-galactose-induced cardiac aging, attenuated cardiac oxidative stress, inflammation and fibrosis, as well as inhibited the activation of TGF-β1/p38/MK2 signaling pathway. These results showed that mangiferin could ameliorate cardiac fibrosis in D-galactose-induced aging rats possibly via inhibiting TGF-β/p38/MK2 signaling pathway.

• Journal of Chest Surgery
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• 제21권1호
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• pp.1-9
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• 1988

The left atrial [LA] dimension and atrial fibrillation [AF] in patients with mitral valvular heart diseases have been thought to be related to hemodynamic burden to the LA depending on severity of stenosis or regurgitation of mitral valve, left ventricular contractility and the heart conditions. If hemodynamic burden persists long, it can affect the LA wall and structural change of the LA wall itself can developed. So the structural change of the LA wall could be thought to be related to the LA dimension and AF. To verify this relation, the LA wall biopsy was performed in 26 patients with rheumatic mitral valvular heart disease at the left atriotomy incision margin which was posterior to the interatrial groove after completion of surgery to the mitral valve such as valve replacement or commissurotomy. Relation of the pathological state of the LA wall to AF and the LA dimension measured by M-mode echocardiography was studied. The conclusions were as follow. 1. There was tendency that degree of fibrosis of myocardium of the LA wall was related to the LA dimension. 2. There was more chance that patients who had severe fibrosis of myocardium of the LA wall had pre and postoperative AF. 3. There was no relation between reduction rate of the LA dimension before and after surgery and degree of fibrosis of myocardium of the LA wall.

• Korean Circulation Journal
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• 제52권4호
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• pp.251-264
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• 2022

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure (HF) cases. The prevalence of HFpEF is increasing due to an aging population with hypertension, diabetes mellitus, and obesity. HFpEF remains a challenging clinical entity due to a lack of effective treatment options. Traditional HF medications have not been shown to reduce mortality of patients with HFpEF, and an implantable cardioverter-defibrillator is not indicated due to normal ejection fraction. Sudden death is the most common mode of death in patients with HFpEF; however, the underlying mechanisms of sudden death are not fully elucidated. Although ventricular arrhythmias are responsible for the majority of sudden deaths in general, their contribution to sudden deaths in HFpEF patients is likely less significant. The mechanisms of ventricular arrhythmias in HFpEF are 1) reduced conduction velocity due to ventricular hypertrophy, 2) delayed repolarization due to potassium current down-regulation, 3) calcium leakage due to altered excitation-contraction coupling, and 4) increased ventricular fibrosis caused by systemic inflammation. Hypertension and subsequent ventricular hypertrophy reduce the conduction velocity in HFpEF hearts via heterogeneous distribution of connexin 43. Delayed repolarization caused by potassium current down-regulation in HFpEF hearts provides a window for early afterdepolarization to trigger ventricular arrhythmias. Altered excitation-contraction coupling in HFpEF can cause calcium to leak and trigger delayed afterdepolarization. Increased systemic inflammation and subsequent ventricular fibrosis provide substrates for re-entry. Further research is warranted to investigate the detailed mechanisms of ventricular arrhythmias in HFpEF.

• 대한한의학방제학회지
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• 제31권3호
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• pp.157-169
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• 2023

Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2002년도 추계학술대회초록집
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• pp.132-132
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• 2002

Mostly, hypercholesterolemia has been focused on atherosclerosis and coronary heart disease and can be produced by intake of high cholesterol diet. However, toxic effects of cholesterol itself on liver and relationship between intake of high cholesterol diet and hepatic fibrosis have not been clearly investigated. Male Wistar rats were fed diet supplemented with 1.0 ％ cholesterol and 0.3 ％ sodium cholate for 12 weeks. Rats were sacrificed at 0, 3, 6, 9 and 12, respectively. Histopathological and blood chemical studies were performed on these animal sets. Total cholesterol, AST, ALT and LDH levels increased from week 3 and maintained around that level throughout the experiment compared to control. However, TG and albumin levels were the same or lower than those of control. Intake of high cholesterol and sodium cholate diet caused hepatic necrosis, macrophage infiltration, steatosis and fibrosis. Following feeding this diet to rats, hepatic necrosis, macrophage infiltration and steatosis markedly increased throughout the experiment, comparing to control. Collagen deposition and myofibroblasts were detected from at week 9 to 12 in the liver. Mast cell increased in proportion to the degree of hepatic damages. In conclusion, these results suggest that intake of high cholesterol diet is a risk factor on hepatic steatosis and fibrosis as well as atherosclerosis and coronary heart disease. Furthermore, this animal model for hepatic fibrosis can be use for application of anti-fibrogenic agents screening in vivo.

• The Korean Journal of Physiology and Pharmacology
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• 제20권5호
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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.

• Journal of Chest Surgery
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• 제20권3호
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• pp.489-497
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• 1987

Six hundred and twenty two cases of open heart surgery were performed at Sejong General Hospital in 1986. And also, 117 cases of non open heart cardiac surgery had been performed during same period. Among the 622 open heart cases, 548 were congenital cardiac diseases and 74 were acquired heart diseases. In congenital heart patients, 422 were acyanotic and 126 were cyanotic. There were 52 cases of infant open heart Surgery below 12 months. Acyanotic group were consisted of 314 VSD, 66 ASD, 13 AVSD, 9 PDA, 8 ASD + PS, 4 AS, and 8 other rare cardiac cases. And cyanotic group were consisted of 84 TOF, 15 DORV, 5 Trilogy, 4 Ebstein`s anomaly, 3 PS + TR, 3 TGA, 3 TAPVR, 3 Pulmonary atresia and 6 other rare cardiac diseases. Majority of the acquired heart cases were valvular heart diseases. And there were also 4 cardiac myxoma and one endomyocardial fibrosis in acquired heart disease group. The operative results were as follows: Overall operative mortality, 5.3%: acyanotic 2.4%: cyanotic 15.8% and acquired heart disease, 8.5%.