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BACKGROUND: The accumulation of lipoprotein and monocyte in the intima of the arterial wall is the most important step of the development of coronary artery disease (CAD). Lipoprotein lipase (LPL) plays an anti-atherogenic role by lipolysis of triglyceride-rich lipoproteins, but, it may also act as a receptor of some lipoproteins and monocyte at the arterial wall and act as a atherogenic molecule. Previous studies showed somewhat contradictory results about the association of CAD and LPL polymorphisms and mutations. Racial and dietary difference may contribute to these contradictory results. In this study, we tried to find out the association of CAD and the genetic variation of the LPL (PvuII RFLP in intron 6, HindIII RFLP in intron 8 and Ser 447 Ter mutation in exon 9) in Korean population. METHOD AND RESULT: CAD patients (n=146), confirmed by coronary angiography and healthy Korean adult volunteers (n=110) were genotyped for PvuII/HindIII RFLP and Ser447Ter mutation of the LPL gene by PCR-digestion method. Between two groups, the genotype frequency of these genetic variations was not different. But, the genetic variations showed different effect on lipid profile and body mass index (BMI) in the CAD group and in the control group. In the CAD group, P1 allele carriers showed higher total cholesterol (P1P1+P1P2:P2P2=216+-51 mg/dl:198+/-38 mg/dl, p=0.039) and higher LDL cholesterol level (P1P1+P1P2:P2P2=143+/-46 mg/dl:126+/-36 mg/dl, p=0.047), and H1 allele carriers had lower Body mass index than non-carriers (23.8+/-2.3 kg/m2 :24.8+/-2.9 kg/m2 , p=0.047). In the control group, the Ser447Ter mutation carriers had higher HDL cholesterol level than non-carriers (59+/-10mg/dl versus 53+/-11mg/dl, p=0.049) and patients with P1 allele showed lower body mass index (P1P1+P1P2: P2P2=23.1+/-2.6 kg/m 2 :24.5+/-2.6 kg/m2 , p=0.006). CONCLUSION: In Korean, PvuII/HindIII RFLP and Ser447Ter mutation was not associated with CAD, and they showed different effect on the lipid profile and on the body mass index according to the study group. These results suggests that the phenotypic characteristics of the LPL gene of the Korean people are different from those of occidental people.
Adult ; Alleles ; Body Mass Index ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Coronary Angiography ; Coronary Artery Disease* ; Coronary Vessels* ; Exons ; Genetic Variation ; Genotype ; Humans ; Introns ; Lipolysis ; Lipoprotein Lipase* ; Lipoproteins* ; Monocytes ; Polymorphism, Restriction Fragment Length ; Volunteers

BACKGROUND AND OBJECTIVES: Angiotensin II (Ang II) has been suggested to accelerate vascular senescence, however the molecular mechanism(s) remain unknown. METHODS: We cultured human coronary artery smooth muscle cells (hCSMCs) and treated Ang II and/or fimasartan. Or we transfected adenoviral vectors expressing CYR61 (Ad-CYR61) or antisense CYR61 (Ad-As-CYR61). Cellular senescence was evaluated senescence-associated β-galactosidase (SA-β-gal) assay. The molecular mechanisms were investigated real-time PCR and western blots. RESULTS: SA-β-gal-positive cells significantly increased in Ang II-treated hCSMCs (5.77±1.43-fold compared with the control). The effect of Ang II was significantly attenuated by pretreatment with the Ang II type 1 receptor blocker, fimasartan (2.00±0.92-fold). The expression of both p53 and p16 senescence regulators was significantly increased by Ang II (p53: 1.39±0.17, p16: 1.19±0.10-fold vs. the control), and inhibited by fimasartan. Cysteine-rich angiogenic protein 61 (CYR61) was rapidly induced by Ang II. Compared with the control, Ad-CYR61-transfected hCSMCs showed significantly increased SA-β-gal-positive cells (3.47±0.65-fold). Upon transfecting Ad-AS-CYR61, Ang II-induced senescence (3.74±0.23-fold) was significantly decreased (1.77±0.60-fold). p53 expression by Ang II was significantly attenuated by Ad-AS-CYR61, whereas p16 expression was not regulated. Ang II activated ERK1/2 and p38 MAPK, which was significantly blocked by fimasartan. ERK and p38 inhibition both regulated Ang II-induced CYR61 expression. However, p53 expression was only regulated by ERK1/2, whereas p16 expression was only attenuated by p38 MAPK. CONCLUSIONS: Ang II induced vascular senescence by the ERK/p38 MAPK–CYR61 pathway and ARB, fimasartan, protected against Ang II-induced vascular senescence.
Aging ; Angiotensin II Type 1 Receptor Blockers ; Angiotensin II ; Angiotensins ; Blotting, Western ; Cell Aging ; Coronary Vessels ; Humans ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; p38 Mitogen-Activated Protein Kinases ; Real-Time Polymerase Chain Reaction ; Receptor, Angiotensin, Type 1

BACKGROUND AND OBJECTIVES: Angiotensin II (Ang II) has been suggested to accelerate vascular senescence, however the molecular mechanism(s) remain unknown. METHODS: We cultured human coronary artery smooth muscle cells (hCSMCs) and treated Ang II and/or fimasartan. Or we transfected adenoviral vectors expressing CYR61 (Ad-CYR61) or antisense CYR61 (Ad-As-CYR61). Cellular senescence was evaluated senescence-associated β-galactosidase (SA-β-gal) assay. The molecular mechanisms were investigated real-time PCR and western blots. RESULTS: SA-β-gal-positive cells significantly increased in Ang II-treated hCSMCs (5.77±1.43-fold compared with the control). The effect of Ang II was significantly attenuated by pretreatment with the Ang II type 1 receptor blocker, fimasartan (2.00±0.92-fold). The expression of both p53 and p16 senescence regulators was significantly increased by Ang II (p53: 1.39±0.17, p16: 1.19±0.10-fold vs. the control), and inhibited by fimasartan. Cysteine-rich angiogenic protein 61 (CYR61) was rapidly induced by Ang II. Compared with the control, Ad-CYR61-transfected hCSMCs showed significantly increased SA-β-gal-positive cells (3.47±0.65-fold). Upon transfecting Ad-AS-CYR61, Ang II-induced senescence (3.74±0.23-fold) was significantly decreased (1.77±0.60-fold). p53 expression by Ang II was significantly attenuated by Ad-AS-CYR61, whereas p16 expression was not regulated. Ang II activated ERK1/2 and p38 MAPK, which was significantly blocked by fimasartan. ERK and p38 inhibition both regulated Ang II-induced CYR61 expression. However, p53 expression was only regulated by ERK1/2, whereas p16 expression was only attenuated by p38 MAPK. CONCLUSIONS Ang II induced vascular senescence by the ERK/p38 MAPK–CYR61 pathway and ARB, fimasartan, protected against Ang II-induced vascular senescence.

BACKGROUND: In acute leukemia patients, several successful methods of expression profiling have been used for various purposes, i.e., to identify new disease class, to select a therapeutic target, or to predict chemo-sensitivity and clinical outcome. In the present study, we tested the peripheral blood of 47 acute leukemia patients in an attempt to identify differentially expressed genes in AML and ALL using a Korean-made 10K oligo-nucleotide microarray. METHODS: Total RNA was prepared from peripheral blood and amplified for microarray experimentation. SAM (significant analysis of microarray) and PAM (prediction analysis of microarray) were used to select significant genes. The selected genes were tested for in a test group, independently of the training group. RESULTS: We identified 345 differentially expressed genes that differentiated AML and ALL patients (FWER < 0.05). Genes were selected using the training group (n=35) and tested for in the test group (n=12). Both training group and test group discriminated AML and ALL patients accurately. Genes that showed relatively high expression in AML patients were deoxynucleotidyl transferase, pre-B lymphocyte gene 3, B-cell linker, CD9 antigen, lymphoid enhancer-binding factor 1, CD79B antigen, and early B-cell factor. Genes highly expressed in ALL patients were annexin A 1, amyloid beta (A4) precursor protein, amyloid beta (A4) precursor-like protein 2, cathepsin C, lysozyme (renal amyloidosis), myeloperoxidase, and hematopoietic prostaglandin D2 synthase. CONCLUSION: This study provided genome wide molecular signatures of Korean acute leukemia patients, which clearly identify AML and ALL. Given with other reported signatures, these molecular signatures provide a means of achieving a molecular diagnosis in Korean acute leukemia patents.
Amyloid ; Antigens, CD79 ; Antigens, CD9 ; B-Lymphocytes ; Cathepsin C ; Diagnosis ; DNA Nucleotidylexotransferase ; Gene Expression* ; Genome ; Humans ; Leukemia* ; Leukemia, Myeloid, Acute ; Lymphoid Enhancer-Binding Factor 1 ; Muramidase ; Peroxidase ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cells, B-Lymphoid ; Prostaglandin D2 ; RNA ; Transcriptome*

The present study represents an analysis of 96 patients with severe aplastic anemia (SAA) treated in Seoul National University Hospital, Seoul, Korea between 1990 and 1999. Twenty-two patients were treated by allogeneic bone marrow transplantation (BMT) from HLA identical sibling donors and 74 by immunosuppressive therapy (IS) with antithymocyte globulin (ATG) or antilymphocyte globulin (ALG). There was no statistical difference between the two treatment groups in age, sex, disease duration, and previous transfusion amount. In the BMT group, grade II-IV acute graft versus host disease (GVHD) develeped in 10% and chronic GVHD occurred in 33% of patient. Only one patient died from complication of transplantation (veno-occlusive disease). Of 74 patients who received IS treatment, 45% achieved a complete or partial response. Twenty patients died among IS treatment group. Major causes of death were hemorrhage (40%) and infection (55%). In the BMT group, the 5-yr overall survival (OS) was 95% after a median follow-up of 42 months. In the IS group, the 5-yr OS was 70% after a median follow-up of 49 months (p=0.04). In conclusion, the long-term survival rates of SAA in Koreans receiving BMT or IS were excellent compared with the Western data. Further evaluation on the prognosis of aplastic anemia in Asians should be done.
Adolescent ; Adult ; Aged ; Anemia, Aplastic/mortality/*therapy ; Antilymphocyte Serum/*administration & dosage ; *Bone Marrow Transplantation ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Graft vs Host Disease ; Human ; Immunosuppressive Agents/*administration & dosage ; Male ; Middle Aged ; Neutrophils/cytology ; Severity of Illness Index ; Survival Analysis

BACKGROUND: Inflammation is an important underlying mechanism in the pathogenesis of atherosclerosis, and an elevated resting heart rate underlies the process of atherosclerotic plaque formation. We hypothesized an association between resting heart rate and subclinical inflammation. METHODS: Resting heart rate was recorded at baseline in the KoGES-ARIRANG (Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population) cohort study, and was then divided into quartiles. Subclinical inflammation was measured by white blood cell count and high-sensitivity C-reactive protein. We used progressively adjusted regression models with terms for muscle mass, body fat proportion, and adiponectin in the fully adjusted models. We examined inflammatory markers as both continuous and categorical variables, using the clinical cut point of the highest quartile of white blood cell count (≥7,900/mm³) and ≥3 mg/dL for high-sensitivity C-reactive protein. RESULTS: Participants had a mean age of 56.3±8.1 years and a mean resting heart rate of 71.4±10.7 beats/min; 39.1% were men. In a fully adjusted model, an increased resting heart rate was significantly associated with a higher white blood cell count and higher levels of high-sensitivity C-reactive protein in both continuous (P for trend <0.001) and categorical (P for trend <0.001) models. CONCLUSION: An increased resting heart rate is associated with a higher level of subclinical inflammation among healthy Korean people.
Adiponectin ; Adipose Tissue ; Atherosclerosis ; Blood Cell Count* ; Blood Cells* ; C-Reactive Protein ; Cohort Studies ; Epidemiology ; Genome ; Heart Rate* ; Heart* ; Humans ; Inflammation ; Leukocyte Count ; Leukocytes ; Male ; Plaque, Atherosclerotic