␤-Catenin is a transcriptional regulator of several genes involved in survival and proliferation. Although previous studies suggest that ␤-catenin may be involved in the process of preconditioning and healing after myocardial infarction (MI), little is known regarding the role of ␤-catenin in cardiomyocytes and cardiac fibroblasts. We investigated the role of ␤-catenin in cardiomyocytes and cardiac fibroblasts and whether ␤-catenin overexpression could reduce MI size. Adenovirus-mediated gene transfer of nonphosphorylatable constitutively active ␤-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 ␤-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. ␤-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.␤-Catenin is known to have dual functions. Membranebound ␤-catenin maintains tissue architecture and cell polarity at adherens junctions by linking the cadherin cytoplasmic tail to the actin cytoskeleton (1). Cytoplasmic ␤-catenin translocates into the nucleus where it forms a complex with transcription factors of Tcf/Lef family and activates the expression of specific genes involved in cell survival and proliferation (1, 2). Glycogen-synthase kinase 3␤ (GSK3␤) 3 constitutively phosphorylates cytoplasmic ␤-catenin resulting in proteosomal degradation (3), and Wnt signaling inhibits GSK3␤, leading to cytoplasmic accumulation of ␤-catenin (4).Although the critical roles of ␤-catenin during development (5) and in neoplastic disease have been well described previously (6), relatively little is known about the role of ␤-catenin in cardiomyocytes and cardiac fibroblasts, which are not only the principal cells comprising the myocardium but also key cells involved in remodeling after myocardial infarction (MI). Recent studies have suggested that ␤-catenin is capable of regulating survival/apoptosis and hypertrophy of cardiomyocytes (7,8). The inactivation of GSK3␤ by statins has been shown to inhibit cardiomyocyte apoptosis (7), whereas activated GSK3␤ was shown to attenuate cardiac hypertrophy in vivo (8). In addition, Wnt/␤-catenin pathways have also been implicated in fibroblast p...

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The objective of this study is to evaluate the changes of diurnal blood pressure pattern after 8 weeks of red ginseng medication (4.5 g/day) by 24 hour ambulatory blood pressure monitoring. In 26 subjects with essential hypertension, 24 hour mean systolic blood pressure decreased significantly (p = 0.03) while diastolic blood pressure only showed a tendency of decline (p = 0.17). The decrease in pressures were observed at daytime (8 A.M.-6 P.M.) and dawn (5 A.M.-7 A.M.). In 8 subjects with white coat hypertension, no significant blood pressure change was observed. We suggest that red ginseng might be useful as a relatively safe medication adjuvant to current antihypertensive medications.

Objective— Glycogen synthase kinase (GSK)-3β is a crucial factor in many cellular signaling pathways and may play an important role in smooth muscle proliferation and apoptosis after angioplasty. Methods and Results— To investigate the effect of GSK-3β modulation on neointima formation, smooth muscle proliferation, and apoptosis after balloon injury in vivo, we delivered adenoviral vectors expressing the constitutively active form of GSK-3β (GSK-S9A: 9th serine switched to alanine) or a control gene into rat carotid arterial segments after balloon injury with a 2F Fogarty catheter. Viral infusion mixtures (5×10 8 pfu) were incubated in the arterial lumen for 20 minutes, and the effects of gene delivery were evaluated 3 days and 2 weeks after gene delivery with morphometry and immunohistochemical staining for proliferating and apoptotic cells. There were no significant differences in intimal, medial, and lumen areas at 3 days after the procedure. However, 2 weeks after gene delivery, the active GSK-3β gene transfer resulted in a significantly lower intima to media ratio (0.29±0.06 versus 0.86±0.09, P <0.01) and a greater lumen area (0.41±0.02 versus 0.31±0.01 mm 2 , P <0.01) compared with the control gene transfected group. This was attributable to a significant reduction in intimal area (0.05±0.01 versus 0.15±0.02 mm 2 , P <0.01), whereas the medial area was similar (0.17±0.01 versus 0.18±0.01 mm 2 , P =0.21). Proliferation index was significantly reduced both at 3 days and 2 weeks in the active GSK-3β gene transferred group (2.97±0.29% versus 5.71±0.50%, P <0.01). In addition, apoptotic index, which was not significantly different between the 2 groups at 3 days, was significantly higher in the active GSK-3β gene transferred group at 2 weeks (3.14±0.68% versus 22.7±1.63%, n=10, P <0.01, for control versus active GSK-3β gene transfer). Conclusions— In vivo delivery of the active GSK-3β gene inhibits smooth muscle proliferation, sustains apoptosis, and reduces neointima formation after balloon injury in rats and may be a future therapeutic target to limit neointima hyperplasia after angioplasty.

Objective-New vessel formation is a dynamic process of attachment, detachment, and reattachment of endothelial cells (ECs) and endothelial progenitor cells (EPCs) with each other and with the extracellular matrix (ECM

Background and Objectives There has been a need for functional status measurement tool with better validity than the existing tools such as New York Heart Association Functional Class. Duke Activity Status Index DASI is a representative example of a tool that was developed to enhance the validity of measurement by asking the patients about the ability to perform specific activities and scoring the response. Because such a tool must be culture-sensitive, it is desirable to use Koreanized version of the tool. No Koreanized version of the functional status measurement tool has been developed yet. The objective of this study is to develop a Korean version of DASI. Materials and Method In the developmental phase, a pilot questionnaire asking the ability to perform specific activity was made with reference to existing tools, such as Specific Activity Scale and DASI. Substitution, correction and addition of items were done through the pilot study. Ninety-nine patients was asked to fill developmental version of questionnaire, then underwent treadmill exercise test. Weight for each items were assigned to optimize the correlation between the calculated index KASI and total treadmill exercise time. Criteria for categorical functional classification were determined to maximize the agreement between KASI-estimated functional class KASIFC and functional class estimated by exercise time. In the validation phase, final version of questionnaire was tested in independent group of 159 patients. The questionnaire was self-administered. Canadian Cardiovascular Society Functional Class CCSFC was estimated by the physician who is in charge of treadmill exercise test. Results In the validation phase, Spearman correlation coefficient between KASI and treadmill exercise time was 0.62 p 0.0001 and between CCSFC and exercise time 0.48 p 0.0001 . KASIFC agreed with functional class estimated by exercise time in 77% of cases, disagreed by 1 class in 20% and by 2 classes in 1%. KASIFC agreed with functional class estimated by exercise time in 77% of cases, disagreed by 1 class in 20% and by 2 classes in 1%. These two methods did not differ significantly in categorical classification. Conclusion KASI is more accurate or at least as accurate as the existing tool in estimation of functional status. The characteristics such as self-administration, availability of outcome as a continuous variable are expected to make it a convenient, efficacious and useful tool in various clinical researches.

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Clinical and angiographic features of Takayasu arteritis were investigated in 129 Korean patients. This disease affects females more frequently than males, in a ratio of 6.6 to 1. Of the total number of patients, 51 were in the third decade, 27 in the fourth decade, and 23 in the second decade. Common clinical symptoms were headache (60%), exertional dyspnea (42%), dizziness (36%), and malaise or weakness (34%). Takayasu arteritis affected the abdominal aorta (46%) and descending thoracic aorta (37%) more frequently than the ascending aorta (1%) and aortic arch (2%) According to Ueno's classification based on aortographic findings, the 129 patients were divided into type I (37), type II (25), and type III (67). Among the 48 patients who had coronary angiography, 11 (23%) showed coronary arterial involvement. Because the clinical features are determined by the extent and severity of the specific artery involved in the occlusive phase of the disease, total aortography including coronary angiography is very important in the initial evaluation of Takayasu arteritis.