[Show abstract][Hide abstract] ABSTRACT: The farnesoid X receptor (FXR) is mainly expressed in liver, intestine and kidney. We investigated whether 6-ethyl chenodeoxycholic acid (6ECDCA), a semisynthetic derivative of chenodeoxycholic aicd (CDCA, an FXR ligand), protects against kidney injury and modulates small heterodimer partner (SHP) in cisplatin-induced kidney injury. Cisplatin inhibited SHP protein expression in the kidney of cisplatin-treated mice and human proximal tubular (HK2) cells; this effect was counteracted by FXR ligand. Hematoxylin and eosin staining revealed the presence of tubular casts, obstructions and dilatations in cisplatin-induced kidney injury, which was attenuated by FXR ligand. FXR ligand also attenuated protein expression of transforming growth factor-β1 (TGF-β1), Smad signaling, and the epithelial-to-mesenchymal transition process, inflammatory markers and cytokines, and apoptotic markers in cisplatin-treated mice. Cisplatin induced NF-κB activation in HK2 cell; this effect was attenuated by pretreatment with FXR ligand. In SHP knockdown by small interfering RNA, cisplatin-induced activation of TGF-β1, p-JNK and Bax/Bcl-2 ratio was not attenuated, while SHP overexpression and FXR ligand inhibited expression of these proteins in cisplatin-pretreated HK2 cells. In conclusion, FXR ligand, 6ECDCA prevents cisplatin-induced kidney injury, the underlying mechanism of which may be associated with anti-fibrotic, anti-inflammatory, and anti-apoptotic effects through SHP induction.
PLoS ONE 01/2014; 9(1):e86553. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The aim of this study was to investigate a useful cardiac biomarker for predicting echocardiographic right ventricular (RV) dysfunction in patients with acute pulmonary embolism (APE). METHODS: A total of 84 patients with APE were divided into two groups: patients with RV dysfunction (group I, n=51, 61.8±15.1 years) versus without RV dysfunction (group II, n=33, 66.8±13.6 years). Cardiac biomarkers were compared between the groups. RESULTS: The level of N-terminal pro-brain-type natriuretic peptide (NT-proBNP), cardiac specific troponin T (cTnt), and I (cTni) was significantly elevated in group I compared to group II, but the level of creatine kinase and high-sensitivity C-reactive protein was not different. By receiver operating characteristic curve analysis, the area under the curve to predict RV dysfunction was 0.912 for NT-proBNP, 0.797 for cTnt, and 0.766 for cTni. The optimal cut-off value to predict RV dysfunction was 620.0pg/mL for NT-proBNP (sensitivity: 90.2%, specificity: 75.8%), 0.016ng/mL for cTnt (sensitivity: 82.4%, specificity: 78.8%), and 0.055ng/mL for cTni (sensitivity: 86.3%, specificity: 66.7%). NT-proBNP>620pg/mL and cTnt>0.016ng/mL were independent predictors of RV dysfunction on multivariate analysis after adjustment for the baseline characteristics. CONCLUSIONS: NT-proBNP, cTnt, and cTni were significant serologic predictors of RV dysfunction in APE. Measurements of NT-proBNP, cTnt, and cTni are simple and useful in the risk stratification or treatment of APE.
Journal of Cardiology 08/2012; · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed to compare the incidence and clinical significance of transient versus persistent acute kidney injury (AKI) on acute ST elevation myocardial infarction (STEMI).
The study was a retrospective cohort of 855 patients with STEMI. AKI was defined as an increase of ≥0.3 mg/dL in creatinine level at any point during hospital stay. The study population was classified into 5 groups: 1) patients without AKI; 2) patients with mild AKI that was resolved by discharge (creatinine change less than 0.5mg/dL compared with admission creatinine during hospital stay, transient mild AKI); 3) patients with mild AKI that did not resolve by discharge (persistent mild AKI); 4) patients with moderate/severe AKI that was resolved by discharge (creatinine change more than 0.5 mg/dL compared with admission creatinine, transient moderate/severe AKI); 5) patients with moderate/ severe AKI that did not resolve by discharge (persistent moderate/severe AKI). We investigated 1-year all-cause mortality after hospital discharge for the primary outcome of the study. The relation between AKI and 1-year mortality after STEMI was analyzed.
AKI occurred in 74 (8.7%) patients during hospital stay. Adjusted hazard ratio for mortality was 3.139 (95% CI 0.764 to 12.897, p=0.113) in patients with transient, mild AKI, and 8.885 (95% CI 2.710 to 29.128, p<0.001) in patients with transient, moderate/severe AKI compared to patients without AKI. Persistent moderate/severe AKI was also independent predictor of 1 year mortality (hazard ratio, 5.885; 95% CI 1.079 to 32.101, p=0.041).
Transient and persistent moderate/severe AKI during acute myocardial infarction is strongly related to 1-year all cause mortality after STEMI.
Yonsei medical journal 07/2011; 52(4):603-9. · 0.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stent thrombosis is a fatal complication in patients who have undergone percutaneous coronary intervention, and discontinuation of anti-platelet agent is a major risk factor of stent thrombosis. We report a rare case of very late stent thrombosis (VLST) following discontinuation of anti-platelet agents in a patient who experienced acute myocardial infarction and essential thrombocytosis. She had undergone implantation of a drug eluting stent (DES) and a bare metal stent (BMS) two and half years prior to her presentation. VLST developed in DES, not in BMS, following interruption of anti-platelet therapy.
[Show abstract][Hide abstract] ABSTRACT: Left circumflex artery (LCX) related acute myocardial infarction (AMI) has been known to be under diagnosed with 12-lead electrocardiogram (ECG). However, there were only a few studies that have focused on the clinical characteristics of LCX-related AMI. We studied the clinical characteristics and hospital mortality in patients with angiographically confirmed LCX-related AMI. A total of 2281 AMI patients with single acutely occluded culprit vessel in coronary angiography (pre-Thrombolysis In Myocardial Infarction flow: 0) were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) from November 2005 to January 2008. These patients were divided into three groups according to culprit vessel [left anterior descending artery (LAD), right coronary artery (RCA), and LCX]. This study showed the patients with LCX-related AMI were less likely to present with ST elevation in ECG (46.3%, 87.0%, and 82.3%; p<0.001) and primary percutaneous coronary intervention (PCI) (43.4%, 78.9%, and 74.5%; p<0.001) and door to balloon time <90 min (31.3%, 52.8%, and 51.0%; p<0.001), compared with LAD and RCA. However, no statistical difference was found in hospital mortality among the three groups. Multivariate analysis showed primary PCI decreased the hospital mortality in patients with occluded coronary artery. In conclusion, AMI patients with an occluded LCX presented with less ST elevation and primary PCI. These results suggest that clinical physicians should be careful with patients presenting with chest pain but apparently normal ECG and must rule out LCX occlusion.
Journal of Cardiology 03/2011; 57(3):290-6. · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Complete blood count is the most widely available laboratory datum in the early in-hospital period after ST-elevation myocardial infarction (STEMI). We assessed the clinical utility of the combined use of hemoglobin (Hb) level and neutrophil-to-lymphocyte ratio (N/L) for early risk stratification in patients with STEMI. We analyzed 801 consecutive patients with STEMI treated with primary percutaneous coronary intervention (PCI) within 12 hours of onset of symptoms. Patients with cardiogenic shock or underlying malignancy were excluded, and 739 patients (63 ± 13 years, 74% men) were included in the final analysis. Patients were categorized into 3 groups using the median value of N/L (3.86) and the presence of anemia (Hb <13 mg/dl in men and <12 mg/dl in women); group I had low N/L and no anemia (n = 272), group II had low N/L and anemia, or high N/L and no anemia (n = 331), and group III had high N/L and anemia (n = 136). There were significant differences on clinical outcomes during 6-month follow-up among the 3 groups. Prognostic discriminatory capacity of combined use of Hb level and N/L was also significant in high-risk subgroups such as patients with advanced age, diabetes mellitus, multivessel coronary disease, low ejection fraction, and even in those having higher mortality risk based on Thrombolysis In Myocardial Infarction risk score. In a Cox proportional hazards model, after adjusting for multiple covariates, group III had higher mortality at 6 months (hazard ratio 5.6, 95% confidence interval 1.1 to 27.9, p = 0.036) compared to group I. In conclusion, combined use of Hb level and N/L provides valuable timely information for early risk stratification in patients with STEMI undergoing primary PCI.
The American journal of cardiology 01/2011; 107(6):849-56. · 3.58 Impact Factor