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Background and objectives Patients with Kawasaki disease (KD) are clinically heterogeneous because its diagnosis is based solely on clinical observation and there are no definitive biomarkers. We dissected the clinical heterogeneity of KD patients using the KD-associated genetic variants. Methods We performed a genetic association analysis in several KD subgroups categorized by clinical characteristics using the KD-associated variants of the B lymphoid tyrosine kinase (BLK; rs6993775) and Fc gamma receptor II a (FCGR2A; rs1801274) in a large number of case (n=1,011) and control (n=4,533) samples. Results BLK and FCGR2A were very significantly associated with KD in Korean KD patients (odds ratio [OR],1.48; p=4.63×10⁻¹¹ for BLK, and OR, 1.26; p=1.42×10⁻⁴ for FCGR2A). However, in KD subgroup analysis, we found that neither BLK nor FCGR2A were associated with either incomplete Kawasaki disease (iKD) type patients or those older than 5 years of age (p>0.2), suggesting that patients with iKD or those older than 5 years of age are a unique subgroup of KD. In genetic association analysis after excluding iKD patients and those older than 5 years old, we found that BLK was associated with all KD subgroups, whereas FCGR2A was specifically associated with male KD patients younger than 1 year of age (OR, 2.22; p=2.35×10⁻⁵). Conclusions KD is a clinically and genetically heterogeneous disease. These findings will provide new insights into the clinical and genetic heterogeneity of KD.

Background and Objectives Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined. Methods Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease. Results Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs). Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p

Background and objectives Hypertension is becoming one of the most common health conditions in children and adolescents due to increasing childhood obesity. We aimed to provide the auscultatory blood pressure (BP) normative reference values for Korean non-overweight children and adolescents. Methods BP measurements in children and adolescents aged 10 to 18 years were performed in the Korean National Health and Nutrition Examination Survey (KNHANES) from 1998 to 2016. BP was measured using a mercury sphygmomanometer. Sex-, age- and height-specific systolic BP (SBP) and diastolic BP (DBP) percentiles were calculated in the non-overweight children (n=10,442). We used the General Additive Model for Location Scale and Shape method to calculate BP percentiles. Results The 50th, 90th, 95th, and 99th percentiles of SBP and DBP tables and graphs of non-overweight children and adolescents aged 10 to 18 years were presented by age and height percentiles. We found that the SBP and DBP at the 95th percentile were well correlated with height. The BP tables presented by height contained BP values from 124 cm to 190 cm for boys and from 120 cm to 178 cm for girls. Boys had higher SBP and DBP. Conclusions We provided the sex-, age- and height-specific auscultatory BP values using the KNHANES big data. These may be useful in diagnosis and treatment of hypertension in Korean children and adolescents.

Background and Objectives Obesity has reached epidemic proportions globally and affects people of all ages. Recent studies have shown that visceral adipose tissue measured by magnetic resonance imaging and/or computed tomography correlates positively with epicardial adipose tissue. Epicardial fat, which is correlated to several metabolic parameters, can be assessed by echocardiography. The aim of this study was to evaluate epicardial fat thickness and other metabolic parameters in obese adolescents and investigate the correlation between epicardial fat thickness and other metabolic parameters in obese adolescents. Subjects and Methods We selected 99 subjects, between ages 15-17 years of age, to be enrolled in this study. Sixty five obese adolescents with a body mass index (BMI) >95 percentile and 34 control subjects were included in this study. Echocardiographic measurements including epicardial fat thickness as well as anthropometric and blood pressure (BP) measurements were performed. The following parameters were estimated: blood glucose, total cholesterol, triglyceride, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, free fatty acid, interleukin-6, tumor necrosis factor-α, leptin, adiponectin and high sensitive C reactive protein. Results The obese group showed a statistically significant correlation with echocardiographic epicardial fat thickness and, BMI, waist circumference, obesity index, fat percentage, systolic BP, insulin level, leptin and adiponectin. Multivariate linear regression analysis showed epicardial fat thickness as the most significant independent parameter to correlate with obese adolescents. Conclusion These data suggest that epicardial fat thickness measured by echocardiography is a practical and accurate parameter for predicting visceral obesity.

Background and objectives Simvastatin's properties are suggestive of a potential pathophysiologic role in pulmonary hypertension. The objectives of this study were to investigate changes of pulmonary pathology and gene expressions, including endothelin (ET)-1, endothelin receptor A (ERA), inducible nitric oxide synthase (NOS2), endothelial nitric oxide synthase (NOS3), matrix metalloproteinase (MMP) 2, tissue inhibitor of matrix metalloproteinases (TIMP) and caspase 3, and to evaluate the effect of simvastatin on monocrotaline (M)-induced pulmonary hypertension. Materials and methods Six week old male Sprague-Dawley rats were treated, as follows: control group, subcutaneous (sc) injection of saline; M group, sc injection of M (60 mg/kg); and simvastatin group, sc injection of M (60 mg/kg) plus 10 mg/kg/day simvastatin orally. Results On day 28, right ventricular hypertrophy (RVH) significantly decreased in the simvastatin group compared to the M group. Similarly, right ventricular pressure significantly decreased in the simvastatin group on day 28. From day 7, the ratio of medial thickening of the pulmonary artery was significantly increased in the M group, but there was no significant change in the simvastatin group. The number of muscular pulmonary arterioles was significantly reduced in the simvastatin group. On day 5, gene expressions of ET-1, ERA, NOS2, NOS3, MMP and TIMP significantly decreased in the simvastatin group. Conclusion Administration of simvastatin exerted weak inhibitory effects on RVH and on the number of muscular pulmonary arterioles, during the development of M-induced pulmonary hypertension in rats. Simvastatin decreased gene expressions on day 5.

Background and Objectives: We sought to determine parameters to guide the decision of retreatment in patients with Kawasaki disease (KD) who remained febrile after initial intravenous immunoglobulin (IVIG). Subjects and Methods: A total of 129 children with KD were studied prospectively. Patients were treated with IVIG 2 to 9 days after the onset of disease. Laboratory measures, such as white blood cell (WBC), percentage of neutrophils, C-reactive protein (CRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP), were determined before and 48 to 72 hours after IVIG treatment. Patients were classified into IVIG-responsive and IVIG-resistant groups, based on the response to IVIG. Results: Of a total of 129 patients, 107 patients (83%) completely responded to a single IVIG therapy and only 22 patients (17%) required retreatment: 14 had persistent fever and 8 had recrudescent fever. There was no significant difference between the groups in age, gender distri bution, and duration of fever to IVIG initiation, but coronary artery lesions developed significantly more often in the resis tant group than in the responsive group (31.8% vs. 2.8%, p=0.000). Compared with pre-IVIG data, post-IVIG levels of WBC, percentage of neutrophils, CRP, and NT-proBNP decreased to within the normal range in the responsive group, whereas they remained high in the resistant group. Multivariate logistic regression indicated that neutrophil counts, CRP, and NT-proBNP were independent parameters of retreatment. Conclusion: Additional therapy at an early stage of the disease should be administered for febrile patients who have high values of CRP, NT-proBNP, and/or neutrophil counts after IVIG therapy. (Ko

Background and Objectives Elevated endothelin (ET)-1 level is strongly correlated with the pathogenesis of pulmonary arterial hypertension (PAH). Expression level of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 is increased in the PAH patients. Ambrisentan, a selective endothelin receptor A (ERA) antagonist, is widely used in PAH therapy. The current study was undertaken to evaluate the effects of ambrisentan treatment in the monocrotaline (MCT)-induced PAH rat model. Methods Rats were categorized into control group (C), monocrotaline group (M) and ambrisentan group (Am). The M and Am were subcutaneously injected 60 mg/kg MCT at day 0, and in Am, ambrisentan was orally administered the day after MCT injection for 4 weeks. The right ventricle (RV) pressure was measured and pathological changes of the lung tissues were observed by Victoria blue staining. Protein expressions of ET-1, ERA, endothelial nitric oxide synthase (eNOS) and NOX4 were confirmed by western blot analysis. Results Ambrisentan treatment resulted in a recovery of the body weight and RV/left ventricle+septum at week 4. The RV pressure was lowered at weeks 2 and 4 after ambrisentan administration. Medial wall thickening of pulmonary arterioles and the number of intra-acinar arteries were also attenuated by ambrisentan at week 4. Protein expression levels of ET-1 and eNOS were recovered at weeks 2 and 4, and ERA levels recovered at week 4. Conclusions Ambrisentan administration resulted in the recovery of ET-1, ERA and eNOS protein expression levels in the PAH model. However, the expression level of NOX4 remained unaffected after ambrisentan treatment.

Background and Objectives: Hypertension develops as a result of cardiac hypertrophy and fibrosis or as a result of exchange of the extracellular matrix. In particular, matrix metalloproteinase (MMP)-3 is a major enzyme involved in the reconstruction of the arterial intima through activation of other MMPs. We analyzed MMP-3 genotypes in hypertensive and normotensive adolescents and sought to determine if a particular genotype is a predictor of cardiovascular complications. Subjects and Methods: Forty-four hypertensive adolescents and 59 healthy adolescents were included in this study. Serum aldosterone, renin, insulin, angiotensin converting enzyme (ACE), insulin, homocysteine, vitamin B12, folate, MMP-1, MMP-2, MMP-3, MMP-9, tissue inhibitors of matrix metalloproteinases (TIMP)-1, and TIMP-2 were measured. MMP-3 genotypes were analyzed using a polymerase chain reaction (PCR) primer. The carotid intima media thickness (IMT), diameter, and brachial ankle pulse wave velocity (baPWV) were evaluated using ultrasound. Results: In hypertensive adolescents, blood pressure, anthropometric data, carotid IMT, baPWV, serum pro-MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were no different between the 6A/6A group and the 5A/6A group. Serum MMP-9 was higher in the 5A/6A group than in the control group. Aldosterone, insulin, and homocysteine were higher in the 6A/6A group than in the control group, and vitamin B12 and folate were lower in the 6A/6A group than in the control group. Conclusion: In conclusion, serum MMP-3 levels were not significantly different in different MMP-3 genotypes in hypertensive adolescents. However, few patients were included in this study. Further investigation is necessary to clarify the relationship between MMP-3 genotype and cardiovascular risk. (Korean Circ J 2009;39:328-334)

Background and Objectives: Kawasaki disease (KD) is an acute inflammatory process affecting the arterial walls that results in panvasculitis. Recent studies have shown that even after resolution of the disease, endothelial dysfunction persists and may progress to atherosclerosis. The pulse wave velocity (PWV) and the ankle-brachial index (ABI) are simple and non-invasive methods for evaluating the degree of atherosclerosis, and are known as the predictors of cardiovascular disease in adults. Carotid intima-media thickness (cIMT) is also known as a predictor of cardiovascular disease. We conducted this study to determine the change in arterial stiffness by measuring the PWV, ABI, and cIMT in children who have recovered from KD. Subjects and Methods: Twenty-five patients with KD and coronary aneurysm were recruited. They all recovered from KD and were normal for more than 8 years. Fifty-five healthy children were evaluated as the control group. Their height, weight, body mass index, and blood pressure (systolic, diastolic, and the mean) were measured. The PWV, ABI, ejection time (ET), and pre-ejection period (PEP) were measured by ultrasonography. The cIMT was measured by ultrasonography. Results: The left brachial ankle PWV was significantly higher in the KD group (1020.6±146.5 cm/sec) than the control group (984.0±96.5 cm/sec). The ABI did not differ between the two groups. There was no difference in PEP/ET and cIMT. Conclusion: The PWV in children who recovered from KD was higher than the control group. Long-term follow up is necessary in children after recovery from KD even if there is no abnormality in echocardiography. (Korean Circ J 2009;39:264-269)

Background and Objectives: This study is aimed at elucidating potential temporal associations between the occurrence of Kawasaki disease (KD) and various viral infections. Subjects and Methods: We obtained monthly patterns of KD from the seventh nationwide survey and viral detection data from the Korea Centers for Disease Control and Prevention from 2009 to 2011 and evaluated temporal correlations between them for each month. The respiratory viruses detected using a multiplex real-time-polymerase chain reaction kit were influenza virus (A/H1N1, A/H3N2, A/H5N1, and B), adenovirus, parainfluenza virus (type 1, 2, 3), respiratory syncytial virus (type A, B), human rhinovirus, human coronavirus (OC43/229E, NL63), human bocavirus, and enterovirus. Results: We obtained data from a total of 13031 patients who were treated for acute KD from 87 hospitals with pediatric residence programs. During this survey, KD showed highest overall incidence in summer and winter seasons and lowest incidence in February and October. We received viral detection data for a total of 14267 patients. Viral detection was highest during winter and spring seasons. The most commonly detected virus was human rhinovirus (32.6%), followed by influenza virus (26.8%). The monthly incidence of KD showed signifi cant correlation with the monthly overall viral detection (p=0.022, r=0.382). In particular, human bocavirus and enterovirus have significant correlations with monthly patterns of KD occurrence (p=0.032 and p=0.007, respectively) and influenza virus correlated with KD occurrence with borderline significance (p=0.063). Conclusion: The temporal association between monthly occurrence of KD and viral detection suggests the etiologic importance of precedent infection in the development of KD. (Korean Circ J 2014;44(4):250-254)

Background and Objectives In Korea, there hasn't been any previous literature that describes auscultatory blood pressure (BP) normative tables for adolescents. Using BP data, from the Korean National Health and Nutrition Examination Survey (KNHANES), we created normative auscultatory BP percentile tables for Korean adolescents. Subjects and Methods A total of 3508 adolescents (boys 1852, girls 1656), aged 10-17 in 2001, 2005 and 2007 from the KNHANES database years, were included. Auscultatory BP measurement was performed, using a Baumanometer Mercury Gravity Sphygmomanometer. Results The mean systolic BP of boys was higher than that of girls in adolescents older than 13 years of age, and the mean diastolic BP of boys was higher than that of girls in those older than 15 years. Systolic and diastolic BP was correlated with weight, height and age. Age-specific normative auscultatory systolic and diastolic BP percentiles for boys and girls were completed. The graph that showed age-specific prehypertensive and hypertensive systolic and diastolic BP for boys and girls was presented. For adolescents, the height-specific auscultatory BP percentiles for boys and girls were completed. A graph that shows the height-specific prehypertensive and hypertensive BP for boys and girls was also made. Conclusion The auscultatory age-and height-specific BP percentiles for Korean adolescents are established. These can be useful in screening the prehypertension and hypertension of Korean adolescents in a clinical setting.

Background and Objectives: At birth, the fetal circulation must immediately adapt to extrauterine life. Our goal was to evaluate perinatal changes in the size of the aorta (Ao) and pulmonary artery (PA), and to investigate factors influencing these changes. Subjects and Methods: Aortic and PA diameters were measured by echocardiography in 50 healthy term babies one day before and 4 to 5 days after birth. Results: Compared with prenatal measurements, the Ao increased (from 7.4±0.6 mm to 8.4±0.6 mm, p

Background and objectives: Failure of vascular smooth muscle apoptosis and inflammatory response in pulmonary arterial hypertension (PAH) is a current research focus. The goals of this study were to determine changes in select gene expressions in monocrotaline (MCT)-induced PAH rat models after human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) transfusion. Materials and methods: The rats were separated into 3 groups i.e., control group (C group), M group (MCT 60 mg/kg), and U group (hUCB-MSCs transfusion) a week after MCT injection. Results: TUNEL assay showed that the U group had significantly lowered positive apoptotic cells in the lung tissues, as compared with the M group. mRNA of caspase-3, B cell leukemia/lymphoma (Bcl)-2, interleukin (IL)-6, tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in the lung tissues were greatly reduced at week 4 in the U group. Immunohistochemical staining of the lung tissues also demonstrated a similar pattern, with the exception of IL-6. The protein expression of caspase-3, Bcl-2 VEGF, IL-6, TNF-α and brain natriuretic peptide in the heart tissues were significantly lower in the U group, as compared with the M group at week 2. Furthermore, the protein expression of VEGF, IL-6 and BNP in the heart tissues were significantly lower in the U group at week 4. Collagen content in the heart tissues was significantly lower in the U group, as compared with M group at weeks 2 and 4, respectively. Conclusion: hUCB-MSCs could prevent inflammation, apoptosis and remodeling in MCT-induced PAH rat models.

Background and Objectives Respiratory symptoms are often observed in children with Kawasaki disease (KD) during the acute phase. The association of respiratory viruses in children with KD was investigated using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) and tissue Doppler echocardiography. Subjects and Methods 138 KD patients were included from January 2010 to June 2013. We compared 3 groups (group 1: n=94, KD without respiratory symptoms; group 2: n=44, KD with respiratory symptoms; and group 3: n=50, febrile patients with respiratory symptoms). Laboratory data were obtained from each patient including N-terminal pro-brain natriuretic peptide (NT-proBNP). Echocardiographic measurements were compared between group 1 and group 2. RT-PCR was performed using nasopharyngeal secretion to screen for the presence of 14 viruses in groups 2 and 3. Results The incidence of KD with respiratory symptoms was 31.8%. The duration of fever was significantly longer, and coronary artery diameter was larger in group 2 than in group 1. Tei index was significantly higher and coronary artery diameter larger in group 2 than group 1. Coronary artery diameter, C-reactive protein levels, platelet count, alanine aminotransferase levels, and NT-pro BNP levels were significantly higher and albumin levels lower in group 2 compared with group 3. Conclusion NT-pro BNP was a valuable diagnostic tool in differentiating KD from other febrile viral respiratory infections. Some viruses were more frequently observed in KD patients than in febrile controls. Tei index using tissue Doppler imaging was increased in KD patients with respiratory symptoms.

In order to perform large-scale genetic studies of Kawasaki disease (KD) in Korea, the Korean Kawasaki Disease Genetics Consortium (KKDGC) was formed in 2008 with 10 hospitals. Since the establishment of KKDGC, there has been a collection of clinical data from a total of 1198 patients, and approximately 5 mL of blood samples per patient (for genomic deoxyribonucleic acid and plasma isolation), using a standard clinical data collection form and a nation-wide networking system for blood sample pick-up. In the clinical risk factor analysis using the collected clinical data of 478 KD patients, it was found that incomplete KD type, intravenous immunoglobulin (IVIG) non-responsiveness, and long febrile days are major risk factors for coronary artery lesions development, whereas low serum albumin concentration is an independent risk factor for IVIG non-responsiveness. In addition, we identified a KD susceptibility locus at 1p31, a coronary artery aneurysm locus (KCNN2 gene), and the causal variant in the C-reactive protein (CRP) promoter region, as determining the increased CRP levels in KD patients, by means of genome-wide association studies. Currently, this consortium is continually collecting more clinical data and genomic samples to identify the clinical and genetic risk factors via a single nucleotide polymorphism chip and exome sequencing, as well as collaborating with several international KD genetics teams. The consortium-based approach for genetic studies of KD in Korea will be a very effective way to understand the unknown etiology and causal mechanism of KD, which may be affected by multiple genes and environmental factors.

Background and Objectives Vascular wall remodeling in pulmonary hypertension can be caused by an aberration in the normal balance between proliferation and apoptosis of endothelial cell in the pulmonary artery. The objective of this study was to evaluate the effect of bosentan on apoptosis in monocrotaline (MCT)-induced pulmonary hypertension. Materials and Methods Sprague-Dawley rats were divided into three groups: control (C) group, M group (MCT 60 mg/kg) and B group (MCT 60 mg/kg plus bosentan 20 mg/day orally). Gene expressions of Bcl (B cell leukemia/lymphoma)-2, caspase-3, complement component (C)-6, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were analyzed by real time polymerase chain reaction and western blot analysis. Results The messenger ribonucleic acid (mRNA) expressions of caspase-3 and VEGF were significantly increased in the M group compared with the C group, and significantly decreased in the B group compared with the M group in week 4. mRNA expression of IL-6 was significantly decreased in weeks 1, 2, and 4 in the B group compared with the M group. mRNA expression of TNF-α was significantly decreased on day 5 and in weeks 1 and 2 in the B group compared with the M group. Conclusion Bosentan may have potential for preventing apoptosis and inflammation.

Background and Objectives We sought to determine whether high-dose aspirin is necessary for the acute therapy of Kawasaki disease (KD) in the intravenous immunoglobulin (IVIG) era. Subjects and Methods Two groups of KD patients treated during the different periods were included. Study group (n=51, treated with IVIG without concomitant use of aspirin in the acute phase) was compared with control group (n=129, treated with IVIG plus high-dose aspirin) with regard to the response to IVIG, duration of fever after IVIG completion, time to C-reactive protein (CRP)

Background and Objectives: The renin angiotensin system seems to play an important role in the development of cardiac and vascular hypertrophy in hypertension. The changes in pathology, and gene expressions of the angiotensin II receptor type 1A (ATIA) and angiotensin converting enzyme (ACE) were investigated in order to explore the effects of losartan in spontaneously hypertensive rat (SHR) models. Materials and Methods: Twelve week-old male Wistar rats were grouped as follows: control (C) group, hypertension (H) group, and losartan (L) group in which SHR was treated with losartan (10 mg/kg/day). Western blot and reverse transcription-polymerase chain reaction analysis regarding seven genes such as endothelin-1, ACE, ATIA, neutrophil cytosolic factor, brain natriuretic peptide, troponin I, endothelial nitric oxide synthase were performed. Results: Systolic blood pressure was significantly decreased in the L group compared with the H group in weeks 3 and 5. ACE and ATIA pro teins in the L group were lower than H group in week 5. Conclusion: Losartan reduced blood pressure, cardiac hypertrophy and protein expressions of ACE and ATIA. Changes of protein expressions were more sensitive than changes in pathology. Further study is needed for the differing doses of losartan in SHR models. (Korean Circ J 2012;42:761-768)

Background and Objectives Obesity is a chronic disease that requires good eating habits and an active life style. Obesity may start in childhood and continue until adulthood. Severely obese children have complications such as diabetes, hypercholesterolemia, hypertension and atherosclerosis. The goal of this study was to determine the effects of exercise programs on anthropometric, metabolic, and cardiovascular parameters in obese children. Subjects and Methods Fifty four obese children were included. Anthropometric data such as blood pressures, body mass index (BMI) and obesity index (OI) were measured. Blood glucose, total cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), high sensitive-CRP (hs-CRP), brachial-ankle pulse wave velocity (BaPWV) and ankle brachial index (ABI) were measured. Physical fitness measurements were done. Obese children were divided into three groups: an aerobic exercise group (n=16), a combined exercise group (n=20), and a control group (n=18). Obese children exercised in each program for 10 weeks while those in the control group maintained their former lifestyle. After 10 weeks, anthropometric data and cardiovascular parameters were compared with the data obtained before the exercise program. Results LDL-C, waist circumference, and systolic blood pressure decreased significantly in the aerobic exercise group compared to the control group (p

Background and Objectives The pathogenesis of hyponatremia (serum sodium

BACKGROUND AND OBJECTIVES Endothelin (ET)-1, a potent endothelium-derived vasoconstrictor peptide, has a potential pathophysiologic role in pulmonary hypertension. Bosentan, a dual ET receptor (ET(A)/ET(B)) antagonist, is efficacious in treatment of pulmonary hypertension. The objectives of this study were to investigate the expression of ET-1 and ET receptor A (ERA) genes and to evaluate the effect of bosentan in monocrotaline (MCT)-induced pulmonary hypertension. MATERIALS AND METHODS Four-week-old male Sprague-Dawley rats were treated as follows: control (n=36), subcutaneous (sc) injection of saline; MCT (n=36), sc injection of MCT (60 mg/kg); and bosentan (n=36), sc injection of MCT (60 mg/kg) plus 25 mg/kg/day bosentan orally. RESULTS Serum ET-1 concentrations in the MCT group were higher than the control group on day 28 and 42. Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan group on day 28 and 42. In addition, the increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on day 14, 28 and 42. The levels of ET-1 and ERA gene expression were significantly increased in the MCT group compared with control group on day 5, and bosentan decreased the expression of ET-1 on day 5. CONCLUSION ET-1 contributes to the progression of cardiopulmonary pathology in rats with MCT-induced pulmonary hypertension. Administration of bosentan reduced ET-1 gene expression in MCT-induced pulmonary hypertension in rats.

Although the clinical manifestations of cardiovascular disease (CVD), such as myocardial infarction, stroke, and peripheral vascular disease, appear from middle age, the process of atherosclerosis can begin early in childhood. The early stage and progression of atherosclerosis in youth are influenced by risk factors that include obesity, hypertension, dyslipidemia, and smoking, and by the presence of specific diseases, such as diabetes mellitus and Kawasaki disease (KD). The existing evidence indicates that primary prevention of atherosclerotic disease should begin in childhood. Identification of children at risk for atherosclerosis may allow early intervention to decrease the atherosclerotic process, thereby preventing or delaying CVD. This review will describe the origin and progression of atherosclerosis in childhood, and the identification and management of known risk factors for atherosclerotic CVD in children and young adults.

Background and Objectives: The renin-angiotensin system (RAS) is a major regulator of blood pressure. The angiotensin II receptor type 1 (AGTR 1) A1166C has been extensively studied in searching for their involvement in the development of hypertension. The aim of this study was to determine the association of the AGTR 1 A1166C marker with essential hypertension in Korean adolescents. Subjects and Methods: Forty hypertensive adolescents were included in this study. The obesity index (OI) and body mass index (BMI) of the subjects were calculated. Blood pressure was measured at the resting state by oscillometric methods. The serum aldosterone, renin, insulin, angiotensin converting enzyme (ACE), homocysteine, vitamin B12 and folate levels were measured. The carotid intima-media thickness (IMT) and diameter and the brachial-ankle pulse wave velocity (baPWV) were evaluated by ultrasound. Polymerase chain reaction (PCR) was conducted to amplify the DNA of each of the study subjects to analyze the polymorphism of AGTR 1 A1166C. Results: The genotypic frequency of AA was 87.5%, that for adenylate cyclase (AC) was 12.5% and no CC type was detected. The serum homocysteine level was higher in the subjects with the AC genotype than that in the subjects with the AA genotype (11.9±2.9 umol/L vs 17.1±4.2 umol/L, respectively). The carotid IMT of the subjects with the AA genotype was greater than that of the subjects with the AC genotype (5.0±0.1 mm vs 8.0±0.2 mm, respectively). Conclusion: In conclusion, the A1166C mutation group had a significantly greater carotid IMT and higher homocysteine levels than the group with the normal genotype of AGTR 1. The AC genotype of A1166C may be useful to predict the presence of early coronary artery disease in hypertensive adolescents. More investigation is necessary to clarify the relation between the A1166C gene and its involvement with coronary artery disease in hypertensive Korean adolescents. (Korean Circ J 2008;38:405-410)

Background and Objectives：Smoking is known to increase arterial stiffness in adults. The pulse wave velocity (PWV) is known as an established index of arterial stiffness. The effects of smoking on the PWV in adolescents have not yet been established. We measured the PWV and ankle-brachial index (ABI) in adolescents to determine the effects of smoking on adolescents. Subjects and Methods：Four hundred twenty-seven adolescents between 14 to 16 years of age were enrolled from three high schools in Seoul, Korea. The study group was comprised of 48 smokers (38 males and 10 females) and 379 nonsmokers (254 males and 125 females). Measurements of the height, weight and body mass index (BMI) were performed. The blood pressures of the extremities, and the PWV, the ABI, the ejection time and the pre-ejection period were measured using an automatic device (VP-1000). Among the smoking group, we investigated the association between the duration of smoking, the age at which smoking started and the total number of cigarettes smoked with the PWV and ABI. Results：The brachial-ankle PWV (baPWV) in the smoking group was higher than that of the non-smoking group, but the difference was not statistically significant. There was no significant difference between the ABI of the two groups. Among the smokers, the heart-brachial PWV (hbPWV) was significantly associated with the duration of smoking and the total number of cigarettes smoked. Conclusion：Our study showed no significant difference in the PWV between the two groups. A longitudinal, long-term investigation is needed to more accurately determine the effects of smoking on adolescents. (Korean Circulation J 2007;37:414-418)

Background and Objectives:The prevalence of pediatric hypertension appears to be increasing, and secondary hypertension is more common in children than in adults. Essential hypertension is increasing in obese adolescents. An elevated blood pressure (BP) during childhood is associated with premature cardiovascular morbidity and mortality in adulthood. Oscillometric devices are convenient and minimize observer error. The purposes of this study were to measure the BP, using an oscillometric device, in relation to age, sex, weight, height and body mass index (BMI), in normal school aged children, and to identify the 95 and 99 percentile values for the diagnosis of hypertension by age group. Subjects and Methods:Between May and June 2005, the oscillometric blood pressure was measured, using a Dinamap monitor (Procare-200, GE, USA), in 9,499 Seoul school children (male 4,993, female 4,506), aged 7-18 years. The BP was measured on the right arm, in the sitting position, using a BP cuff having a width of 40-50% of the arm circumference. The mean and 5, 10, 25, 50, 75, 90, 95 and 99 percentile values and percentile curves of the systolic and diastolic BP were obtained in relation to age, sex, height, weight and BMI. Results:The systolic and diastolic BP levels were significantly increased in relation to age, height, weight and BMI. A correlation analysis showed that the BP levels were significantly correlated with weight (r=0.553), followed by height (r=0.491), BMI (r=0.470) and age (r=0.445) in males, and significantly correlated with weight (r=0.332), followed by height (r=0.317), BMI (r=0.286) and age (r=0.213) in females. Conclusion:Percentile values and percentile curves for the systolic and diastolic BP were obtained in normal children. These data will be useful in the diagnosis and treatment of pediatric hypertension. (Korean Circulation J 2006;36:744-752)

Background and Objectives：Cardiac troponin T (cTnT has been used as a very sensitive marker of cardiac injury caused by ischaemia, myocarditis, and cardiomyopathy. After cardiac injury, the fetal cTnT isoform expression in the heart and serum cTnT increases. To investigate the increased levels of serum cTnT, and the expression of fetal cTnT isoform in the heart, that can predict myocardial injury, we measured serum cTnT levels and the fetal cTnT isoform expression at various time points during the early phase of myocardial toxicity induced by adriamycin (ADR in rat. Materials and Methods：Male Sprague-Dawley rats were injected, intraperitoneally, with ADR (5 mg/kg twice a week for 2 weeks. Control rats were injected with saline. Serum cTnT levels were measured by ELISA. The ratio of fetal/adult (F/A cTnT isoform expression (% was semi-quantified by RT-PCR using total RNA from frozen hearts. Results：Serum cTnT levels did not increase by 1 week after ADR injection, but increased significantly after 2 weeks. The ratio of F/A cTnT in the heart significantly increased from day 1, peaked at 1 week and persisted until the end of 2 week. Conclusion：The expression of the fetal cTnT isoform occurred from 1 day after ADR injection when the serum cTnT levels were still normal. Although the serum cTnT level is a very sensitive, and an early marker, of cardiac damages, the fetal cTnT isoform expression in the endomyocardial biopsy specimen may be a more sensitive and an earlier marker in the ADR-induced myocardial damage. (Korean Circulation J 2002;32( ( ( (6 :485-491