• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.515-525
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• 2023

The most common heart valve disorder is calcific aortic valve stenosis (CAVS), which is characterized by a narrowing of the aortic valve. Treatment with the drug molecule, in addition to surgical and transcatheter valve replacement, is the primary focus of researchers in this field. The purpose of this study is to determine whether niclosamide can reduce calcification in aortic valve interstitial cells (VICs). To induce calcification, cells were treated with a pro-calcifying medium (PCM). Different concentrations of niclosamide were added to the PCM-treated cells, and the level of calcification, mRNA, and protein expression of calcification markers was measured. Niclosamide inhibited aortic valve calcification as observed from reduced alizarin red s staining in niclosamide treated VICs and also decreased the mRNA and protein expressions of calcification-specific markers: runt-related transcription factor 2 and osteopontin. Niclosamide also reduced the formation of reactive oxygen species, NADPH oxidase activity and the expression of Nox2 and p22^phox. Furthermore, in calcified VICs, niclosamide inhibited the expression of β-catenin and phosphorylated glycogen synthase kinase (GSK-3β), as well as the phosphorylation of AKT and ERK. Taken together, our findings suggest that niclosamide may alleviate PCM-induced calcification, at least in part, by targeting oxidative stress mediated GSK-3β/β-catenin signaling pathway via inhibiting activation of AKT and ERK, and may be a potential treatment for CAVS.

• IMMUNE NETWORK
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• v.16 no.1
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• pp.26-32
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• 2016

Aortic valve stenosis is a heart disease prevalent in the elderly characterized by valvular calcification, fibrosis, and inflammation, but its exact pathogenesis remains unclear. Previously, aortic valve stenosis was thought to be caused by chronic passive and degenerative changes associated with aging. However, recent studies have demonstrated that atherosclerotic processes and inflammation can induce valvular calcification and bone deposition, leading to valvular stenosis. In particular, the most abundant cell type in cardiac valves, valvular interstitial cells, can differentiate into myofibroblasts and osteoblast-like cells, leading to valvular calcification and stenosis. Differentiation of valvular interstitial cells can be trigged by inflammatory stimuli from several immune cell types, including macrophages, dendritic cells, T cells, B cells, and mast cells. This review indicates that crosstalk between immune cells and valvular interstitial cells plays an important role in the development of aortic valve stenosis.

• Journal of Chest Surgery
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• v.22 no.6
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• pp.1001-1012
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• 1989

In 1968, Carpentier and his associates introduced glutaraldehyde as a compound for preparing cardiac tissue valve, and this technique has provided a considerably more suitable and durable tissue valve substitute. To increase further durability of valve tissue, Reis and his colleagues designed a flexible stent to reduce the stress on the heterogeneous tissue valve mounted. However with the advent of more innovative mechanical valve currently, many bioprosthetic valves are being substituted by mechanical valves at our department of cardiothoracic surgery because of bioprosthetic valve failure. Main cause of bioprosthetic valves failure were calcification or/and tear of tissue valves. The purpose of this retrospective study is to clarify the relationship between the patients clinical profile during implantation of tissue valves and pathologic features of the failed bioprosthetic valve. From March, 1982 through June, 1988, 53 bioprosthetic heart valves that had been ex-planted from 45 patients at the department of cardiac surgery of Yonsei University Hospital were subjected to this study. The patients were 10 to 65 year-old [mean age: 30.3 yr] with 17 males and 28 females. Re-replacements of prosthetic valves were carried out twenty nine in mitral position, eight in aortic position and eight in both aortic and mitral position simultaneously. The grading and location for calcification of valves were verified by radiograms. The calcification of the explanted valves leaflets was graded from 0 to 4 plus according to Cipriano and associates method. The types of tear and perforation of leaflet were classified into four types as Ishihara has adopted initially in 1981. In younger age group under thirty three years, explanted tissue valves were significantly more affected in terms of grades of severity of valve calcification as compared with older age group [p < 0.035]. Valve calcification appeared more severe in male as compared to female [p< 0.002]. Ionescu-Shiley bovine pericardial bioprosthetic valves showed more severe calcification than Hancock porcine tissue valves [p< 0.035]. Calcium deposit was found very prevalent at the area of commissural attachment [86 % of all]. Type I of valve rupture was shown to be related with simultaneous calcification. However, the relation of explanted valve position, duration of implanted prosthetic valve, atrial fibrillation and anticoagulant therapy to the severity of bioprosthetic valve calcification were not significantly clear statistically [p > 0.05].

• Journal of Chest Surgery
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• v.23 no.4
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• pp.622-639
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• 1990

The use of aortic valve homograft has been developed since 1962 when Ross and Barratt - Boyes independently replaced a diseased aortic valve with an orthotopically inserted homograft valve. And also surgical treatment of complex congenital cardiac malformations utilizing homograft extracardiac conduit has been tried with better result than any other prosthetic material. The present study was undertaken to clarify the safety tissue viability, sterility, after following our protocol of procurement of heart, dissection of aortic and pulmonic homograft, sterilization, cryopreservation, thawing and dilution, and transplantation on experimental animal, sheep. Tissue viability of valve and great artery was assessed by tissue culture. Sterility was evaluated by bacterial and fungal culture. The method used was proven no deleterious effect on the integrity of the valve. Tissue culture of valve tissue before, and after cryopreservation process resulted that active fibroblast growth was observed from homograft sterilized with antibiotics. And culture of the transplanted homograft from sacrificed animal showed active fibroblast growth. Pathologic examination of implanted valve tissue from sacrificed sheep showed mild calcification and minor change, but there were moderate and severe calcification of wall of great arteries.

• Journal of Chest Surgery
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• v.46 no.3
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• pp.212-215
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• 2013

A 79-year-old man was admitted to Samsung Changwon Hospital due to chest pain and dyspnea. The ejection fraction was 31% and mean pressure gradient between the left ventricle and aorta was 69.4 mmHg on echocardiography. Chest computed tomography showed severe calcification of the ascending aorta. Aortic valve replacement was successfully performed using a thoracic endovascular aortic repair balloon catheter without classic aortic cross clamping. The patient was discharged on the eleventh postoperative day.

• Journal of the Korean Society of Radiology
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• v.84 no.6
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• pp.1324-1336
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• 2023

Purpose This study aimed to compare the diagnostic performance of cardiac CT and transthoracic echocardiogram (TTE) depending on the degree of valvular calcification and bicuspid aortic valve (BAV) subtype. Materials and Methods This retrospective study included 266 consecutive patients (106 with BAV and 160 with tricuspid aortic valve) who underwent cardiac CT and TTE before aortic valve replacement. Cardiac CT was used to evaluate the morphology of the aortic valve, and a calcium scoring scan was used to quantify valve calcium. The aortic valves were classified into fused and two-sinus types. The diagnostic accuracy of cardiac CT and TTE was calculated using a reference standard for intraoperative inspection. Results CT demonstrated significantly higher sensitivity, negative predictive value, and accuracy than TTE in detecting BAV (p < 0.001, p < 0.001, and p = 0.003, respectively). The TTE sensitivity tended to decrease as valvular calcification increased. The error rate of TTE for CT was 10.9% for the twosinus type of BAV and 28.3% for the fused type (p = 0.044). Conclusion Cardiac CT had a higher diagnostic performance in detecting BAV than TTE and may help diagnose BAV, particularly in patients with severe valvular calcification.

• Journal of Chest Surgery
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• v.52 no.5
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• pp.368-371
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• 2019

A unicuspid aortic valve is a rare congenital malformation that frequently presents with valvular dysfunction and dilatation or aortic aneurysm, requiring combined aortic valve surgery and aortic repair. Some patients show severe valve calcification extending into the interventricular septum, possibly resulting in damage to the conduction system during debridement for valve replacement. We present a rare case of severe aortic stenosis with a unicommissural unicuspid aortic valve diagnosed by preoperative transesophageal echocardiography in a 36-year-old man. After composite graft replacement of the aortic valve, aortic root, and ascending aorta, a permanent pacemaker was placed because of postoperative complete heart block.

• Journal of Chest Surgery
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• v.48 no.5
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• pp.359-363
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• 2015

The comprehensive aortic root and valve reconstruction (CARVAR) technique comprises two main procedures, which are aortic root reduction using prosthetic rings and neo-leaflet reconstruction using a pericardial patch. Although concerns about durability of the pericardial neo-leaflet have been raised in the CARVAR technique, complications related to leaflet reconstruction have not been reported to date. The present report describes two cases of complications associated with leaflet reconstruction. After resecting the reconstructed leaflets, aortic valve replacement was performed in the patients. Careful and close follow-up is required for patients who had undergone CARVAR surgery, and aortic valve surgery should be performed in a timely manner if needed.

• Journal of Chest Surgery
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• v.19 no.1
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• pp.92-100
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• 1986

Results of reoperation for tissue valve failure were presented with review of current knowledge. Through January 1986, 19 patients required reoperation: 18 had undergone mitral, 2 aortic, and 1 tricuspid valve. Primary tissue failure was the main cause of tissue valve failure: it occurred in 18 valves [15 mitral, 2 aortic, and 1 tricuspid] at a mean postoperative interval of 54-25 months [range 29-120]. During the same period, 2 patients required reoperation for prosthetic valve endocarditis, 1 for paravalvular leakage. The types of valves failed were 12 lonescu-Shiley valves, 5 Hancock valves, and 1 Carpentier-Edwards valve. All 6 patients younger than 15 years of age at first operation had been implanted with lonescu-Shiley valves and failed after a mean interval of 35 months. In contrast, 11 patients older than 15 years had been implanted with 5 Hancock, 6 lonescu-Shiley, and 1 Carpentier-Edwards valve initially, and eventually failed after mean intervals of 81, 53, 47 months each other. The kinds of valves used at reoperation were 8 lonescu-Shiley, 4 Bjork-Shiley, and 6 St. Jude Medical valves for primary tissue failure cases and 3 lonescu-Shiley valves for the other 3 cases. Overall mortality at reoperation was 10%: 5.6% for primary tissue failure, 50% for prosthetic valve endocarditis. In 15 cases [all mitral] primary tissue failure were caused by calcification associated with or without leaflet destruction or fibrous ingrowth, and in 2 cases [all aortic] caused by cusp perforation and tearing without any evidence of calcification. In conclusion: 1 primary tissue failure is the main cause of reoperation in patients with tissue valve failure; 2. the majority of the failed valves is in mitral position; 3. leaflet calcification is the leading pathology of primary tissue failure; 4, reoperation for tissue valve failure may be a major concern, although the mortality is low; 5. the limited durability of tissue valve suggests its use be restricted to selected cases.

• Journal of Chest Surgery
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• v.18 no.4
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• pp.655-662
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• 1985

From January 1985 to July 1985, prosthetic heart valves were replaced in 5 patients at Keimyung University Dongsan Medical Center. The patients included three women and two men ranging in age from 22 to 41 years. Three mitral valve replacements, one aortic valve replacement and one double valve replacement [mitral and aortic valve replacement] were done at the first valve operations. Reoperation were performed 2 to 76 months after the first operations, Prosthetic valve endocarditis occurred in 3 patients, early in one and late in two and primary valve failure occurred in 2 patients. In operative findings, vegetation in prosthetic valve endocarditis and calcification in primary valve failure were found. All except one had relatively successful operative results. One died of early fungal prosthetic valve endocarditis due to relapsed prosthetic valve endocarditis with heart failure and block.