Jang-Whan Bae

β-Catenin Overexpression Reduces Myocardial Infarct Size through Differential Effects on Cardiomyocytes and Cardiac Fibroblasts

β-Catenin is a transcriptional regulator of several genes involved in survival and proliferation. Although previous studies suggest that β-catenin may be involved in the process of preconditioning and healing after myocardial infarction (MI), little is known regarding the role of β-catenin in cardiomyocytes and cardiac fibroblasts. We investigated the role of β-catenin in cardiomyocytes and cardiac fibroblasts and whether β-catenin overexpression could reduce MI size. Adenovirus-mediated gene transfer of nonphosphorylatable constitutively active β-catenin (Ad-catenin) decreased apoptosis in cardiomyocytes and cardiac fibroblasts with increased expression of survivin and Bcl-2. Although Ad-catenin increased the percentage of cells in the S phase with enhanced expression of cyclin D1 and E2 in both cell types, the increase in cell number was only evident in cardiac fibroblasts, whereas hypertrophy and binuclear cells were more prominent in cardiomyocytes. All of these effects of β-catenin gene transfer were blocked by inhibition of its nuclear translocation. Furthermore, Ad-catenin enhanced the expression of vascular endothelial growth factor in both cells and induced differentiation of cardiac fibroblasts into myofibroblasts. In a rat MI model, injection of Ad-catenin into the infarct border zone resulted in a significantly decreased MI size with anti-apoptotic effect and cell cycle activation in both cardiomyocytes and myofibroblasts. β-Catenin may play an important role in the healing process after MI by promoting survival and cell cycle not only in cardiomyocytes but also in cardiac fibroblasts with its differentiation into myofibroblasts.

Effects of bone marrow derived mesenchymal stem cells transplantation in acutely infarcting myocardium

Cellular cardiomyoplasty (CCM) is considered to be a novel therapeutic approach for post‐myocardial infarction (MI) heart failure. In this study, the functional effects of cultured mesenchymal stem cells (MSCs) transplantation and the associated histopathologic changes were evaluated in a rat model of MI.

Discovering Medical Knowledge using Association Rule Mining in Young Adults with Acute Myocardial Infarction

The knowledge discovery has been widely applied to mine significant knowledge from medical data. Nevertheless, previous studies have produced large numbers of imprecise patterns. To reduce the number of imprecise patterns, we need an approach that can discover interesting patterns that connote causality between antecedent and consequence in a pattern. In this paper, we propose association rule mining method that can discover interesting patterns that include medical knowledge in Korean acute myocardial infarction registry that consists of 1,247 young adults collected by 51 participating hospitals since 2005. Proposed method can remove imprecise patterns and discover target patterns that include associations between blood factors and disease history. The association that blood factors affect to disease history is defined as target pattern. In our experiments, the interestingness of a target pattern is evaluated in terms of statistical measures such as lift, leverage, and conviction. We discover medical knowledge that glucose, smoking, triglyceride total cholesterol, and creatinine are associated with diabetes and hypertension in Korean young adults with acute myocardial infarction.

Protective Effects of Peroxiredoxin on Hydrogen Peroxide Induced Oxidative Stress and Apoptosis in Cardiomyocytes

Background and Objectives The redox system is an important anti-oxidative system composed of thioredoxin, thioredoxin reductase, and peroxiredoxin (PRx). The fine details of PRx expression and its protective effects in various cells in cardiovascular tissue under oxidative stress created by hydrogen peroxide have not been fully elucidated. Subjects and Methods Oxidative stress was induced by adding hydrogen peroxide at 0.25 mM for 2 hours to rat neonatal cardiomyocytes (rCMCs), rat vascular smooth muscle cells (rVSMCs), and human umbilical vein endothelial cells (HUVECs). Apoptosis was quantified by flow cytometry and the expression patterns of the six PRx isoforms were evaluated by western blotting in the three cell lines after hydrogen peroxide stimulation. Apoptosis and the cell survival signal pathway were evaluated by PRx1 gene delivery using lentiviral vector in hydrogen peroxide stimulated rCMCs versus green fluorescence protein gene delivery. Results Hydrogen peroxide induced 25% apoptosis in rCMCs. Furthermore, the PRx1 and 5 isoforms were found to be overexpressed in hydrogen peroxide treated rCMCs, and PRx1 overexpression by gene delivery was found to reduce hydrogen peroxide induced rCMCs apoptosis significantly. In addition, this effect was found to originate from cell survival pathway modification. Conclusion Hydrogen peroxide induced significant oxidative stress in rCMCs, rVSMCs, and HUVECs, and PRx1 overexpression using a lentiviral vector system significantly reduced hydrogen peroxide induced rCMCs apoptosis by upregulation of cell survival signals and downregulation of apoptotic signals. These findings suggest that PRx1 could be used as a treatment strategy for myocardial salvage in conditions of oxidative stress.

A case of sparganosis that presented as a recurrent pericardial effusion.

Sparganosis is caused by a larval tapeworm of the genus Spirometra, which commonly invades subcutaneous tissue, but less frequently invades muscle, intestines, spinal cord, and the peritoneopleural cavity. The authors managed a female patient who presented with a recurrent pericardiopleural effusion and peripheral eosinophilia. The anti-sparganum-specific IgG serum level was significantly higher than normal control levels. In this patient, sparganosis was caused by the ingestion of raw frogs in an effort to control her thyroid disease. The recurrent pericardiopleural effusion and peripheral eosinophilia were controlled by 3 consecutive doses of praziquantel (75 mg/kg/day). The patient is doing well 4 years after presentation. Sparganosis should be considered a rare, but possible cause of recurrent pericardial effusion and peripheral eosinophilia. Immunoserologic testing using enzyme linked immunosorbent assays can be helpful in diagnosing human sparganosis, especially in cases without a subcutaneous lump or mass. Praziquantel is an alternative treatment for sparganosis in surgically-unresectable cases.

The PPARγ Agonist Protects Cardiomyocytes from Oxidative Stress and Apoptosis via Thioredoxin Overexpression

Oxidative stress has been implicated in the pathogenesis of various cardiovascular diseases, including ischemic heart disease and heart failure. The peroxisome proliferator-activated receptor gamma (PPARγ) agonist improves insulin sensitivity and limits tissue inflammation and cellular apoptosis, but there are few data on the relationship between the PPARγ agonist, rosiglitazone (RSG), and the thioredoxin (TRx) system in oxidatively stressed cardiomyocytes (CMCs). Here we provide evidence that the PPARγ agonist RSG protects rat CMCs from hydrogen peroxide (H2O2)-induced apoptosis by TRx overexpression. The expression levels of pAkt/Akt, pErk/Erk, survivin, Bcl-2/Bax-α, and manganese-superoxide dismutase were increased by RSG pretreatment in H2O2-injured rat CMCs. On the contrary, the expression levels of caspase-3 and p53 were decreased by RSG pretreatment. These effects of RSG were reversed by chemical inhibitors of TRx and the PPARγ antagonist. This suggests that RSG protects rCMCs from H2O2-induced oxidative stress through TRx overexpression and a PPARγ-dependent mechanism.

Ischemic Postconditioning during Primary Percutaneous Coronary Intervention: The POST Randomized Trial

Background— Ischemic postconditioning has been reported to reduce infarct size in patients with ST-segment–elevation myocardial infarction. However, cardioprotective effects of postconditioning have not been demonstrated in a large-scale trial. Methods and Results— We performed a multicenter, prospective, randomized, open-label, blinded end-point trial. A total of 700 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction within 12 hours after symptom onset were randomly assigned to the postconditioning group or to the conventional primary PCI group in a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow as follows: The angioplasty balloon was positioned at the culprit lesion and inflated 4 times for 1 minute with low-pressure (<6 atm) inflations, each separated by 1 minute of deflation. The primary end point was complete ST-segment resolution (percentage resolution of ST-segment elevation >70%) measured at 30 minutes after PCI. Complete ST-segment resolution occurred in 40.5% of patients in the postconditioning group and 41.5% of patients in the conventional PCI group (absolute difference, −1.0%; 95% confidence interval, −8.4 to 6.4; P=0.79). The rate of myocardial blush grade of 0 or 1 and the rate of major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) at 30 days did not differ significantly between the postconditioning group and the conventional PCI group (17.2% versus 22.4% [P=0.20] and 4.3% versus 3.7% [P=0.70], respectively). Conclusion— Ischemic postconditioning did not improve myocardial reperfusion in patients with ST-segment–elevation myocardial infarction undergoing primary PCI with current standard practice. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00942500.Background —Ischemic postconditioning has been reported to reduce infarct size in patients with ST-segment elevation myocardial infarction (STEMI). However, cardioprotective effects of postconditioning have not been demonstrated in a large-scale trial. Methods and Results —We performed a multicenter, prospective, randomized, open-label, blinded endpoint trial. A total of 700 patients undergoing primary percutaneous coronary intervention (PCI) for STEMI within 12 hours after symptom onset were randomly assigned to the postconditioning group or the conventional primary PCI group in a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow as follows: the angioplasty balloon was positioned at the culprit lesion, and inflated 4 times for 1 minute with low-pressure ( 70%) measured at 30 minutes after PCI. Complete ST-segment resolution occurred in 40.5% of patients in the postconditioning group and 41.5% of patients in the conventional PCI group (absolute difference, -1.0%; 95% confidence interval, -8.4% to 6.4%; P =0.79). The rate of myocardial blush grade of 0 or 1 and the major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) at 30 days did not differ significantly between the postconditioning group and the conventional PCI group (17.2% versus 22.4%, P =0.20, and 4.3% versus 3.7%, P =0.70, respectively). Conclusions —Ischemic postconditioning did not improve myocardial reperfusion in patients with STEMI undergoing primary PCI with current standard practice. Clinical Trial Registration Information —http://ClinicalTrials.gov. Identifier: [NCT00942500][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00942500&atom=%2Fcirculationaha%2Fearly%2F2013%2F09%2F25%2FCIRCULATIONAHA.113.001690.atom

Expression Pattern of the Thioredoxin System in Human Endothelial Progenitor Cells and Endothelial Cells Under Hypoxic Injury

Background and Objectives The thioredoxin (TRx) system is a ubiquitous thiol oxidoreductase pathway that regulates cellular reduction/oxidation status. Although endothelial cell (EC) hypoxic damage is one of the important pathophysiologic mechanisms of ischemic heart disease, its relationship to the temporal expression pattern of the TRx system has not yet been elucidated well. The work presented here was performed to define the expression pattern of the TRx system and its correlation with cellular apoptosis in EC lines in hypoxic stress. These results should provide basic clues for applying aspects of the TRx system as a therapeutic molecule in cardiovascular diseases. Subjects and Methods Hypoxia was induced with 1% O2, generated in a BBL GasPak Pouch (Becton Dickinson, Franklin Lakes, NJ, USA) in human endothelial progenitor cells (hEPC) and human umbilical vein endothelial cells (HUVEC). Apoptosis of these cells was confirmed by Annexin-V: Phycoerythrin flow cytometry. Expression patterns of TRx; TRx reductase; TRx interacting protein; and survival signals, such as Bcl-2 and Bax, in ECs under hypoxia were checked. Results Apoptosis was evident after hypoxia in the two cell types. Higher TRx expression was observed at 12 hours after hypoxia in hEPCs and 12, 36, 72 hours of hypoxia in HUVECs. The expression patterns of the TRx system components showed correlation with EC apoptosis and cell survival markers. Conclusion Hypoxia induced significant apoptosis and its related active changes of the TRx system were evident in human EC lines. If the cellular impact of TRx expression pattern in various cardiovascular tissues under hypoxia or oxidative stress was studied meticulously, the TRx system could be applied as a new therapeutic target in cardiovascular diseases, such as ischemic heart disease or atherosclerosis.

A Case of Severe Aortic Valve Regurgitation Caused by an Ascending Aortic Aneurysm in a Young Patient With Autosomal Dominant Polycystic Kidney Disease and Normal Renal Function

Aortic aneurysm is one several well-known cardiovascular complications in patients with autosomal dominant polycystic kidney disease (ADPCKD). Commonly affected site of aortic aneurysm and its related dissection in ADPCKD is abdominal aorta. Long standing hypertension, haemodialysis, old age are closely related with discovering of aortic aneurysm and dissection in ADPCKD. However, thoracic aortic aneurysms and its related severe aortic regurgitations (ARs) are rare in younger patients suffering from ADPCKD, especially ones who have normal renal function. Here, we report a case involving a 27-year-old Asian male patient with severe AR due to an ascending aneurysm of the thoracic aorta associated with ADPCKD. The patient had normal renal function without Marfans habitus. The AR and thoracic aortic aneurysm were corrected surgically.

Serum thioredoxin 1 level has close relation with myocardial damage amount in acute myocardial infarction patients.

Thioredoxin-1 (Trx-1) is one of important anti-oxidative molecules to overcome the oxidative stress. The aim of the present study is to investigate the clinical relationship between serum concentration of Trx-1 on the pre-percutaneous coronary intervention (prePCI) and myocardial damage amount in the patients with acute myocardial infarction with the culprit lesion in only the left anterior descending artery on coronary angiography (n = 100). Initial value of creatine kinase (CK) was 368.3 ± 531.4 U/L, and MB isoenzyme of CK (CK-MB) level was 22.92 ± 33.8 ng/mL, and cardiac specific troponin T (cTnT) level was 0.61 ± 1.6 ng/mL. Positive correlations were observed between prePCI Trx-1 level and initial CK (P = 0.005, r = 0.281), and cTnT (P < 0.001, r = 0.453), peak CK (P = 0.001, r = 0.316) in all patients, but the statistical relation was observed only in ST segment elevation myocardial infarction (STEMI) patients (P = 0.008, r = 0.329 for initial CK, P = 0.001, r = 0.498 for initial cTnT, P = 0.005, r = 0.349 for peak CK), not in Non-STEMI patients. Conclusively, we consider prePCI serum Trx-1 as a predictor for myocardial damage amount in patients with STEMI.