The Melatonin Signaling Pathway in a Long-Term Memory In Vitro Study.

The activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) via phosphorylation in the hippocampus is an important signaling mechanism for enhancing memory processing. Although melatonin is known to increase CREB expression in various animal models, the signaling mechanism between melatonin and CREB has been unknown in vitro. Thus, we confirmed the signaling pathway between the melatonin receptor 1 (MT1) and CREB using melatonin in HT-22 cells. Melatonin increased MT1 and gradually induced signals associated with long-term memory processing through phosphorylation of Raf, ERK, p90RSK, CREB, and BDNF expression. We also confirmed that the calcium, JNK, and AKT pathways were not involved in this signaling pathway by melatonin in HT-22 cells. Furthermore, we investigated whether melatonin regulated the expressions of CREB-BDNF associated with long-term memory processing in aged HT-22 cells. In conclusion, melatonin mediated the MT1-ERK-p90RSK-CREB-BDNF signaling pathway in the in vitro long-term memory processing model and increased the levels of p-CREB and BDNF expression in melatonin-treated cells compared to untreated HT-22 cells in the cellular aged state. Therefore, this paper suggests that melatonin induces CREB signaling pathways associated with long-term memory processing in vitro.

Prognostic Usefulness of Tricuspid Annular Diameter for Cardiovascular Events in Patients With Tricuspid Regurgitation of Moderate to Severe Degree.

Functional tricuspid regurgitation (TR) is frequently encountered. Current guidelines recommend the surgical correction of severe TR only at the time of left valve surgery despite emphasizing the enlarged tricuspid annulus (TA) dimension. We attempted to evaluate the relation between TA dimension and clinical outcomes of moderate or severe TR. A total of 213 patients (mean age 68 years, women 68%) with moderate or severe TR secondary to left-sided valve surgery, nonvalvular disease, or isolated primary TR were retrospectively identified and classified into tertiles of TA dimension. Cardiovascular (CV) outcomes were defined as a composite of hospitalization for worsening heart failure (HF), stroke, and CV death over a median follow-up of 3.4 years. Upper and lower tertiles of TA dimension had high frequencies of left-sided valve surgery and isolated primary TR, respectively. TA dimension was correlated with TR severity assigned as color Doppler grade and systolic tissue Doppler imaging of the tricuspid valve (TDI s'). During follow-up, there were 87 (41%) occurrences of primary outcomes: 65 HFs (31%), 13 CV deaths (6%), and 9 strokes (4%). There was a high frequency of adverse outcomes in the upper tertile. TA dimension and TDI s' were independently related to outcomes. An enlarged TA dimension was associated with outcomes irrespective of subgroups according to type or severity of TR and TDI s' (p = 0.21, p = 0.77, p = 0.15 for interaction). A cut-off value of 4.0 cm for TA dimension was best for CV event occurrence. When assessing clinical CV outcomes, TA dimension should be considered, even in moderate TR.

No Association of the rs17822931 Polymorphism in ABCC11 with Breast Cancer Risk in Koreans.

ABCC11 is reported to be associated with breast cancer. However, whether ABCC11 polymorphisms relate to breast cancer risk remains unclear. This study aimed to evaluate any association of a single nucleotide polymorphism (SNP), rs17822931, in ABCC11 with breast cancer in Koreans. Genomic DNA samples of 170 women with breast cancer and 100 controls were assessed for SNP rs17822931 of ABCC11 by single-strand conformation polymorphism (SSCP) and DNA sequencing. A 27-bp deletion (Δ27) of ABCC11 was analyzed by PCR amplification. The genotype of SNP rs17822931 was confirmed to be AA in all samples from breast cancer patients and Δ27 was found in none of the samples. Our finding indicated that the SNP rs17822931 in ABCC11 is not associated with breast cancer. However, this study does provide information on fundamental genetic aspects of ABCC11 with regard to breast cancer risk in Koreans.

Bio-optics based sensation imaging for breast tumor detection using tissue characterization.

The tissue inclusion parameter estimation method is proposed to measure the stiffness as well as geometric parameters. The estimation is performed based on the tactile data obtained at the surface of the tissue using an optical tactile sensation imaging system (TSIS). A forward algorithm is designed to comprehensively predict the tactile data based on the mechanical properties of tissue inclusion using finite element modeling (FEM). This forward information is used to develop an inversion algorithm that will be used to extract the size, depth, and Young's modulus of a tissue inclusion from the tactile data. We utilize the artificial neural network (ANN) for the inversion algorithm. The proposed estimation method was validated by a realistic tissue phantom with stiff inclusions. The experimental results showed that the proposed estimation method can measure the size, depth, and Young's modulus of a tissue inclusion with 0.58%, 3.82%, and 2.51% relative errors, respectively. The obtained results prove that the proposed method has potential to become a useful screening and diagnostic method for breast cancer.

Characteristics of function-anatomy mismatch in patients with coronary artery disease.

BACKGROUND AND OBJECTIVES: Coronary lesions with mismatched functional and anatomical significance are not uncommon. We assessed the accuracy and predictors of mismatch between fractional flow reserve (FFR) and quantitative coronary angiography (QCA) analyses in patients with coronary lesions. SUBJECTS AND METHODS: A total of 643 lesions with pre-interventional FFR and QCA measurements were consecutively enrolled and divided into four groups using FFR ≤0.80 and percent diameter stenosis (%DS) ≥50% as cutoffs for functional and anatomical significance, respectively. Accordingly, FFR >0.80 and DS ≥50%, and FFR ≤0.80 and DS <50% defined false-positive (FP) and false-negative (FN) lesions, respectively. RESULTS: Overall, 40.4% (260/643) of the lesions were mismatched, and 51.7% (218/414) and 18.3% (42/229) were FP and FN lesions, respectively. In a multivariate analysis, independent predictors of FP were non-left anterior descending artery location {odds ratio (OR), 0.36; 95% confidence interval (CI), 0.28-0.56; p<0.001}, shorter lesion length (OR, 0.96; 95% CI, 0.95-0.98; p<0.001), multi-vessel disease (OR, 0.47; 95% CI, 0.30-0.75; p=0.001), and larger minimal lumen diameter by QCA (OR, 2.88; 95% CI,1.65-5.00; p<0.001). Independent predictors of FN were multi-vessel disease (OR, 1.82; 95% CI, 1.24-5.27; p=0.048), aging (OR, 0.96; 95% CI, 0.93-0.99; p=0.034), smoking (OR, 0.36; 95% CI, 0.14-0.93; p=0.034), and smaller reference vessel diameter by QCA (OR, 0.30; 95% CI, 0.10-0.87; p=0.026). CONCLUSION: A mismatch between FFR and angiographic lesion severity is not rare in patients with coronary artery disease; therefore, an angiography-guided evaluation could under- or over-estimate lesion severity in specific lesion subsets.

Long-term outcomes of intravascular ultrasound-guided implantation of bare metal stents versus drug-eluting stents in primary percutaneous coronary intervention.

BACKGROUND/AIMS: While drug-eluting stents (DESs) have shown favorable outcomes in ST-segment elevation myocardial infarction (STEMI) compared to bare metal stents (BMSs), there are concerns about the risk of stent thrombosis (ST) with DESs. Because intravascular ultrasound (IVUS) guidance may help optimize stent placement and improve outcomes in percutaneous coronary intervention (PCI) patients, we evaluated the impact of IVUS-guided BMS versus DES implantation on long-term outcomes in primary PCI. METHODS: In all, 239 STEMI patients received DES (n = 172) or BMS (n = 67) under IVUS guidance in primary PCI. The 3-year incidence of major adverse cardiac events (MACEs) including death, myocardial infarction (MI), target vessel revascularization (TVR), and ST was evaluated. RESULTS: There was no difference in all cause mortality or MI. However, the incidence of TVR was 23.9% with BMS versus 9.3% with DES (p = 0.005). Thus, the number of MACEs was significantly lower with DES (11.0% vs. 29.9%; p = 0.001). The incidence of definite or probable ST was not different (1.5% vs. 2.3%; p = 1.0). IVUS-guided DES implantation (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.08 to 0.78; p = 0.017), stent length (HR, 1.03; 95% CI, 1.00 to 1.06; p = 0.046), and multivessel disease (HR, 3.01; 95% CI, 1.11 to 8.15; p = 0.030) were independent predictors of MACE. CONCLUSIONS: In patients treated with primary PCI under IVUS guidance, the use of DES reduced the incidence of 3-year TVR versus BMS. However, all cause mortality and MI were similar between the groups. The incidence of ST was low in both groups.

The efficacy of the cystatin C based glomerular filtration rate in the estimation of safe contrast media volume.

BACKGROUND AND OBJECTIVES: The risk of contrast-induced nephropathy (CIN) is significantly influenced by baseline renal function and the amount of contrast media (CM). We evaluated the usefulness of the cystatin C (CyC) based estimated glomerular filtration rate (eGFRCyC) in the prediction of CIN and to determine the safe CM dosage. SUBJECTS AND METHODS: We prospectively enrolled a total of 723 patients who received percutaneous coronary intervention (PCI) and investigated the clinical factors associated with the development of CIN. Renal function was calculated as eGFRCyC and a modified diet in the renal disease (MDRD) equation, respectively. Systemic exposure of CM was calculated as CM volume to eGFR ratio. We conducted a regression analysis to evaluate the predictive role of CM volume to eGFRCyC for the risk of CIN. RESULTS: The incidence of CIN was 4.0% (29/723). The patients with CIN had a lower hemoglobin level, decreased renal function, and a higher CyC value, and had greater CM exposure. Through multivariate regression analyses, hemoglobin {odds ratio (OR) 0.743, p=0.032}, CM volume/eGFRCyC (OR 1.697, p=0.006) and CM volume/MDRD (OR 2.275, p<0.001) were found to be independent predictors for CIN. In the receiver operating characteristic curve analysis, fair discrimination for CIN was found at a CM volume/eGFRCyC level of 4.493 (C-statics=0.814), and at this value, the sensitivity and specificity were 79.3% and 80.0%, respectively. CONCLUSION: Both the CM volume/MDRD and CM volume/eGFRCyC method would be simple, useful indicators for determining the safe CM-dose based on eGFR value before PCI. However, there was no significantly different predictive value between creatinine and CyC based GFR estimations.

Risk factors between patients with lone and non-lone atrial fibrillation.

Clinical factors such as tall stature, lean body mass, obstructive sleep apnea, alcohol or caffeine, smoking, endurance sports, and genetic factors are proposed as risk factors for lone atrial fibrillation (LAF). The KORAF (KORean Atrial Fibrillation) study is a retrospective multicenter registry that enrolled 3,570 consecutive atrial fibrillation (AF) patients. Data on risk factors were available for 2,133 patients, of whom 398 (18.7%) were identified as having LAF. In univariate analysis, patients with LAF were more likely to be men (82.4% vs 59.8%, P < 0.001) and current smokers (25.9% vs 15.6%, P < 0.01), alcohol drinkers (55.3% vs 31.2%, P < 0.01) and frequent consumers of caffeinated beverages (> 2 cups/day) (31.7% vs 19.3%, P < 0.01), and have a family history of AF (9.0% vs 2.6%, P < 0.001) than the non-LAF patients. Multivariate analysis showed that male gender (OR, 2.30; 95% CI, 1.61-3.27, P < 0.01), family history of AF (OR, 3.12; 95% CI, 1.91-5.12, P < 0.01), current alcohol use (OR, 2.01; 95% CI, 1.46-2.76, P < 0.01), and frequent caffeinated beverage consumption (OR, 1.66; 95% CI, 1.20-2.29, P < 0.01) were independently associated with LAF. In Korean patients, LAF is more closely associated with male gender, family history of AF, current alcohol and frequent caffeinated beverage consumption than non-LAF.

Optical-based artificial palpation sensors for lesion characterization.

Palpation techniques are widely used in medical procedures to detect the presence of lumps or tumors in the soft breast tissues. Since these procedures are very subjective and depend on the skills of the physician, it is imperative to perform detailed a scientific study in order to develop more efficient medical sensors to measure and generate palpation parameters. In this research, we propose an optical-based, artificial palpation sensor for lesion characterization. This has been developed using a multilayer polydimethylsiloxane optical waveguide. Light was generated at the critical angle to reflect totally within the flexible and transparent waveguide. When a waveguide was compressed by an external force, its contact area would deform and cause the light to scatter. The scattered light was captured by a high-resolution camera and saved as an image format. To test the performance of the proposed system, we used a realistic tissue phantom with embedded hard inclusions. The experimental results show that the proposed sensor can detect inclusions and provide the relative value of size, depth, and Young's modulus of an inclusion.

TNF-α polymorphisms and coronary artery disease: association study in the Korean population.

Coronary artery disease (CAD) results from atherosclerosis, a chronic inflammatory disease mediated in part by proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α), which is expressed by atherosclerotic plaques. In this study, we investigated whether TNF-α gene promoter polymorphisms affect the incidence of CAD in Koreans by genotyping. 404 Control subjects and 197 patients who previously received a coronary artery stent for the G/A, C/T, and C/A polymorphisms at position -238, -857 and -863, respectively. The G/G, G/A and A/A genotypes at position -238 occurred in 85.8%, 14.2% and 0% CAD patients and 91.8%, 7.9% and 0.3% control subjects, respectively. The G/A polymorphisms at position -238 were significantly associated with CAD when assuming a dominant model of inheritance (OR = 1.87; 95% CI = 1.10-3.20; P = 0.02), and A allele carriers had a significantly increased risk of developing CAD relative to the G allele (OR = 1.74; 95% CI = 1.04-2.92; P = 0.03). However, the polymorphisms at positions -857 and -863 were not associated with CAD. Haplotype-based analysis revealed the CAD and control groups differed significantly in the frequencies of haplotype ACC at positions -238, -857 and -863 (OR = 1.77; 95% CI = 1.05-2.98; P = 0.03). This was confirmed by multivariate analysis after adjusting body mass index and the presence of diabetes and hypertension (OR = 2.06; 95% CI = 1.15-3.68; P = 0.015). Thus, the -238A allele of TNF-α is associated with an increased risk of CAD and could be used as predictor for CAD in Koreans. Further studies are needed to elucidate the clinical implications of these findings.

Potentials of cystatin C and uric acid for predicting prognosis of heart failure.

Few studies have explored the clinical potentials of combined Cystatin C (Cys) and uric acid (UA) in heart failure (HF). The authors evaluated Cys and UA as predictors of clinical outcomes compared with conventional renal biomarkers. This prospective cohort study included 587 HF patients presenting with dyspnea. At admission, Cys, UA, and other renal measures including serum urea nitrogen (BUN), creatinine (Cr), and glomerular filtration rate (GFR) were obtained. The primary endpoint was the composite of cardiac death and rehospitalization for worsening HF. During a 25-month median follow-up period, 68 patients experienced clinical outcomes: 9 cardiac deaths and 59 HFs. They showed higher BUN and Cr values and lower GFR. Within these parameters, Cys and UA had the most favorable area under the curves, and patients with Cys ≥0.8 mg/L and UA ≥6.6 mg/dL showed more frequent events. The net reclassification improvement analysis showed the combination of Cys and UA had a greater incremental effect for cardiac prognosis. On multivariate Cox hazard analysis, Cys and UA were independent predictive markers for clinical outcomes. In HF patients presenting with dyspnea, Cys and UA appear to be more useful predictors of clinical events than other renal measures.

Metachronous double primary cancer after diagnosis of gastric cancer.

PURPOSE: The pattern of double primary cancers after treatment for gastric cancer is important for a patient's survival. MATERIALS AND METHODS: We analyzed the clinicopathologic data of 214 gastric cancer patients from October 1996 to November 2007 with regard to metachronous second primary cancers. RESULTS: Out of 5,778 patients with gastric cancer, metachronous second primary cancers occurred in 214 patients. The median age was 61.8 years, the number of male and female patients was 140 (65.4%), 74 (34.6%), respectively. The median time to the occurrence of second cancers after diagnosis of the first was 39.2 months (standard deviation, 31.2 months). The most common cancer was colorectal cancer, which occurred in 44 patients (20.6%), and lung cancer in 33 patients (15.4%), hepatocellular carcinoma in 26 patients (12.1%), ovarian cancer in 15 patients (7.0%), cervical cancer in 12 patients (7.0%), breast cancer in 11 patients (5.1%), and esophageal cancer in 11 patients (5.1%). The observed/expected (O/E) ratio showed a significant increase in colorectal (1.25), male biliary (1.60), ovarian (8.72), and cervical cancer (3.33) with primary gastric cancer. After five years from diagnosis of gastric cancer, secondary cancer occurred in 50 patients (23.4%), and breast cancer, prostate cancer, laryngeal cancer, lung cancer, and hepatocellular carcinoma were the most frequent. CONCLUSION: The O/E ratio showed a significant increase in colorectal, male biliary, ovarian, and cervical cancer with primary gastric cancer, and second primary cancer as the main cause of death for these patients. A follow-up examination for metachronous double primary cancer is needed in order to improve the survival time in patients with gastric cancer.

Ovarian tumor-associated carcinoid heart disease presenting as severe tricuspid regurgitation.

Carcinoid heart disease is characterized by heart valve dysfunction as well as carcinoid symptomatology. We report a case of carcinoid heart disease associated with a primary ovarian tumor. A 60-year-old woman presented for dyspnea evaluation with a history of facial flushing, telangiectatic skin changes, and pitting edema of both lower extremities. Chest radiography showed cardiomegaly, and echocardiography revealed an isolated, severe tricuspid regurgitation without left-sided valvular dysfunction. The tricuspid leaflets were severely retracted and shortened, resulting in poor coaptation. Furthermore, mild pulmonary valve stenosis and moderate regurgitation were found along with this deformation. The 24-hour urine analysis revealed an increased level of 5-hydroxyindoleacetic acid, and an ovarian tumor was apparent on computed tomography images. The mass was surgically removed, and the patient was diagnosed as having a primary ovarian carcinoid tumor. She was treated with chemotherapy and regularly followed-up with supportive treatments, deferring surgical correction.

Prevalence of electrocardiographic findings suggestive of sudden cardiac death risk in 10,867 apparently healthy young Korean men.

BACKGROUND: The objective of this study was to determine the prevalence of electrocardiographic (ECG) findings suggestive of sudden cardiac death risk in apparently healthy young Korean men. METHODS: We administered questionnaires that elicited personal and family histories and performed ECGs on 10,867 male subjects (mean age, 20.9 years). The subjects with abnormal ECG findings underwent echocardiography, a treadmill test, Holter monitoring, a flecainide provocation test, or an electrophysiologic study (EPS) according to the ECG findings and histories. RESULTS: Of the subjects, 5.95% had left ventricular hypertrophy on ECG, but no subjects had hypertrophic cardiomyopathy by echocardiography. The percentage of subjects with a Brugada ECG pattern was 0.90%. We identified one subject with a positive result on the flecainide provocation test. The percentage of subjects with a preexcitation ECG was 0.17%. In two of the subjects, supraventricular tachycardia was induced in the EPS. Of the subjects, 0.05% had epsilon waves, but there were no subjects with arrhythmogenic right ventricular dysplasia/cardiomyopathy by echocardiography. The percentage of subjects with long QT intervals was 0.02%, but there were no arrhythmias on the treadmill test or Holter monitoring. CONCLUSIONS: The prevalence of a Brugada ECG pattern in apparently healthy young men is higher in Korea than other countries.

Incidence and predictors of silent embolic cerebral infarction following diagnostic coronary angiography.

BACKGROUND: Coronary angiography (CAG) is an invasive diagnostic procedure, which could lead to procedure related complications. One of the well known post-procedural complications is cerebral embolic infarction with or without symptoms. Silent embolic cerebral infarction (SECI) has clinical significance because it can progress to a decline in cognitive function and increase the risk of dementia in the long term. The aim of this study was to detect the incidence and predictors of SECI after diagnostic CAG using diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: A total of 197 patients with coronary artery disease who underwent DW-MRI for evaluation of intracranial vasculopathy before coronary artery bypass graft surgery were retrospectively enrolled in the present study. DW-MRI was performed within 48 h after diagnostic CAG. SECI was diagnosed as presence of focal bright high signal intensity in DW-MRI. Patients were divided into groups according to presence/absence of SECI (+ SECI vs. - SECI, respectively). The clinical and angiographic characteristics were analyzed and independent predictors were evaluated. RESULTS: Of the 197 patients, SECI occurred in 20 patients (10.2%) after diagnostic CAG. Age, female gender, frequency of underlying atrial fibrillation, extent of coronary disease, and fluoroscopic time during diagnostic CAG were not different between the + SECI and - SECI groups. Left ventricular ejection fraction was significantly lower in the + SECI group than in the - SECI group (45.9 ± 8.5% vs. 51.4 ± 13.1%, p=0.014) and performance rate of internal mammary artery (IMA) angiography was significantly higher in the + SECI group compared with the - SECI group (85% vs. 37.2%, p<0.001). By multivariate analysis, performing IMA angiography was the only predictor of SECI (OR=14.642; 95% CI=3.201 to 66.980, p=0.001). CONCLUSIONS: The incidence of SECI after diagnostic CAG was not infrequent. Diagnostic CAG with IMA angiography may increase the risk of SECI.

The coffee diterpene kahweol sensitizes TRAIL-induced apoptosis in renal carcinoma Caki cells through down-regulation of Bcl-2 and c-FLIP.

Kahweol, a coffee-specific diterpene, found in the beans of Coffea arabica, has potent anti-carcinogenic, anti-tumor, and anti-inflammatory properties. TRAIL is a potential anti-cancer compound that induces apoptosis in a wide variety of cancer cells, but not in most normal human cell types. In the present study, we show that kahweol sensitizes human renal cancer cells, but not normal human mesangial cells, to TRAIL-mediated apoptosis. Moreover, treatment with a combination of kahweol and TRAIL induces significant apoptosis in various cancer cell types, thus presenting an attractive novel strategy for cancer treatment. Our experiments show that treatment with a combination of kahweol and TRAIL-induced apoptosis, and stimulated of DEVDase activity, DNA fragmentation, and cleavage of PARP, which was prevented by pretreatment with z-VAD, indicative of cell death via a caspase-dependent pathway. Kahweol-induced down-regulation of Bcl-2 and ectopic expression of Bcl-2 led to attenuation of kahweol plus TRAIL-mediated apoptosis, indicative of Bcl-2 involvement in the apoptotic process. In addition, the c-FLIP and caspase signal pathways seem to play a crucial role in apoptosis triggered by the combination of kahweol and TRAIL in Caki cells. Our results collectively demonstrate that down-regulation of Bcl-2 and c-FLIP contributes to the sensitizing effect of kahweol on TRAIL-mediated apoptosis in cancer cells.

Support Vector Regression-based Model to Analyze Prognosis of Infants with Congenital Muscular Torticollis.

OBJECTIVES: Congenital muscular torticollis, a common disorder that refers to the shortening of the sternocleidomastoid in infants, is sensitive to correction through physical therapy when treated early. If physical therapy is unsuccessful, surgery is required. In this study, we developed a support vector regression model for congenital muscular torticollis to investigate the prognosis of the physical therapy treatent in infants. METHODS: Fifty-nine infants with congenital muscular torticollis received physical therapy until the degree of neck tilt was less than 5°. After treatment, the mass diameter was reevaluated. Based on the data, a support vector regression model was applied to predict the prognoses. RESULTS: 10-, 20-, and 50-fold cross-tabulation analyses for the proposed model were conducted based on support vector regression and conventional multi-regression method based on least squares. The proposed methodbased on support vector regression was robust and enabled the effective analysis of even a small amount of data containing outliers. CONCLUSIONS: The developed support vector regression model is an effective prognostic tool for infants with congenital muscular torticollis who receive physical therapy.

Orphan nuclear receptor small heterodimer partner inhibits angiotensin II- stimulated PAI-1 expression in vascular smooth muscle cells.

Angiotensin II is a major effector molecule in the development of cardiovascular disease. In vascular smooth muscle cells (VSMCs), angiotensin II promotes cellular proliferation and extracellular matrix accumulation through the upregulation of plasminogen activator inhibitor-1 (PAI-1) expression. Previously, we demonstrated that small heterodimer partner (SHP) represses PAI-1 expression in the liver through the inhibition of TGF-beta signaling pathways. Here, we investigated whether SHP inhibited angiotensin II-stimulated PAI-1 expression in VSMCs. Adenovirus-mediated overexpression of SHP (Ad- SHP) in VSMCs inhibited angiotensin II- and TGF-beta-stimulated PAI-1 expression. Ad-SHP also inhibited angiotensin II-, TGF-beta- and Smad3-stimulated PAI-1 promoter activity, and angiotensin II-stimulated AP-1 activity. The level of PAI-1 expression was significantly higher in VSMCs of SHP(-/-) mice than wild type mice. Moreover, loss of SHP increased PAI-1 mRNA expression after angiotensin II treatment. These results suggest that SHP inhibits PAI-1 expression in VSMCs through the suppression of TGF-beta/Smad3 and AP-1 activity. Thus, agents that target the induction of SHP expression in VSMCs might help prevent the development and progression of atherosclerosis.

Comparison of long-term outcomes following sirolimus-eluting stent vs paclitaxel-eluting stent implantation in patients with long calcified coronary lesions.

BACKGROUND: Although previously reported studies on coronary calcification mainly focused on its presence or absence in discrete focal target lesions, calcified coronary lesions (CCL) angiographically present as diffuse long lesions in some patients. The aim of our study was to evaluate the long-term efficacy of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) on long CCL. METHODS: A total of 122 patients with 134 lesions (77 patients with 88 lesions for SES and 45 patients with 46 lesions for PES) were enrolled from 3 centers. Long CCL was defined visually as a culprit lesion with type B or C that was mainly due to coronary calcification with > 20 mm in total length by coronary angiography. Clinical follow-up was performed at 1 year and angiographic follow-up at 6 to 9 months after procedure. Major adverse coronary events (MACE) were defined as all-cause death, myocardial infarction (MI), and repeat target-lesion revascularization (TLR). RESULTS: There were no statistically significant differences in baseline, procedural, or angiographic characteristics and in 1-year rates of all-cause death, MI, and TLR between the 2 groups (all P = NS [not significant]). Likewise, the cumulative incidence of MACE at 1 year was similar between the 2 groups (7.8% of patients in the SES group vs 4.4% of patients in the PES group, respectively, P = NS). In patients who underwent follow-up angiography, the angiographic binary restenosis rate was 6.2% in the SES group vs 12.1% in the PES group, respectively (P = NS). CONCLUSION: In patients with long CCL, both SES and PES were comparably effective in either angiographic or clinical long-term outcomes.