Two intracellular signal pathways mediated by cAMP and protein kinase C (PKC) were involved in the regulation of FN gene expression (Lee et al., Exp. Mol. Med. 30: 240, 1998). In this study, a possible involvement of protein phosphatase-dependent pathways in the regulation of FN gene expression was investigated by using protein phosphatase type 2B (PP2B) inhibitors, cyclosporin A and ascomycin. Both cyclosporin A and ascomycin increased the levels of FN mRNA in WI-38 human lung fibroblasts and the SV40-transformed WI-38 cells but not in MC3T3-E1 osteoblasts. The expression of FN appears to increase from six hours up to 48 hours after treatment suggesting that it is not an immediate effect. In addition, this effect required a new protein synthesis. Neither cyclosporin A nor ascomycin affects the phorbol myristate acetate (PMA)-induced stimulation of FN gene expression and the same result occurred in vice versa suggesting the mechanism of PMA and cyclosporin A/ascomycin in the regulation of FN gene expression may share a common downstream pathway. Taken together, this study suggests that PP2B is involved in the regulation of FN gene expression in normal and transformed fibroblasts but not in osteoblasts.
Animal ; Calcineurin/antagonists & inhibitors* ; Cell Line, Transformed ; Cell Transformation, Viral ; Cyclosporine/pharmacology* ; Enzyme Inhibitors/pharmacology ; Fibroblasts ; Fibronectins/metabolism ; Fibronectins/genetics* ; Gene Expression Regulation* ; Human ; Lung/cytology ; Mice ; Osteoblasts ; Tacrolimus/pharmacology ; Tacrolimus/analogs & derivatives*

BACKGROUND: Acute thrombotic occlusion after percutaneous coronary intervention (PCI) is a serious complication that provokes acute myocardial infarction, cardiac death or emergent bypass surgery. The role of fibrinogen, C-reactive protein (CRP) and lipoprotein (a) [Lp(a)] in the patients who developed acute thrombotic occlusion after PCI was investigated. METHODS: The patients with acute coronary syndrome who underwent PCI at Chonnam National University Hospital between Jan. 1999 and Jun. 2000 were divided into two groups according to the occurrence of acute thrombotic occlusion: patients with thrombotic occlusion after PCI (Group I; 62.3+/-8.8 years, M:F=19:8) and patients without thrombotic occlusion after PCI (Group II; 59.6+/-10.6 years, M:F=271:95). Clinical and angiographic characteristics, levels of fibrinogen, CRP and Lp(a) were compared between two groups. RESULTS: There were no significant differences in the level of fibrinogen between two groups. The patients with elevated CRP (>0.5mg/dL) were more common in Group I than those in Group II (88.9% vs. 42.3%, p=0.0001) and the value of CRP was higher in Group I than in Group II (4.97+/-5.18 mg/dL vs. 2.27+/-4.23 mg/dL, p=0.002). The patients with high Lp(a) (>30mg/dL) were more prevalent in Group I than those in Group II (44.4% vs 18.6%, p=0.001). There were no significant differences in the risk factors for coronary artery disease, except for diabetes mellitus (Group I : Group II, 40.7% : 16.9%, p=0.002). Thrombolysis in Myocardial Infarction (TIMI) flow of Group I was lower than in Group II (p=0.0001). Multiple regression analysis after the adjustment for age, sex and other cardiovascular risk factors, diabetes mellitus, low TIMI flow, high CRP and Lp(a) were independently associated with the occurrence of acute thrombotic occlusion (p=0.008, 0.0001, 0.031, 0.035, respectively). CONCLUSION:The elevated values of CRP and Lp(a), diabetes mellitus, and low TIMI flow are significant predictive factors for the acute thrombotic occlusion in patients with acute coronary syndrome after PCI.
Acute Coronary Syndrome ; C-Reactive Protein* ; Coronary Artery Disease ; Death ; Diabetes Mellitus ; Fibrinogen* ; Humans ; Jeollanam-do ; Lipoprotein(a)* ; Lipoproteins* ; Myocardial Infarction ; Percutaneous Coronary Intervention* ; Risk Factors ; Thrombosis

BACKGROUND: Lipoprotein (a) [Lp(a)] contains apolipoprotein(a), which is a structural homologue of plasminogen and competes with it for binding sites. It also acts by increasing plasminogen activator inhibitor-1 expression. The objective of this study was to evaluate the relationship between Lp(a) levels and restenosis rate after successful coronary stent placement. METHODS: The study included 306 patients who underwent coronary stent placement and follow-up coronary angiogram at Chonnam National University Hospital from August 1996 to June 2000. Restenosis rate was analyzed according to the level of Lp(a); Group I with high Lp(a) (n=7, Lp(a) 36 mg/dL, 58.98.8 years, female: 35.1%) and Group II with low Lp(a) (n=29, Lp(a) < 36 mg/dL, 57.79.8 years, female: 18.8%). RESULTS: 1) There was no significant differences in risk factors of atherosclerosis, clinical diagnosis, the number of involved coronary artery, left ventricular function, angiographic lesion characteristics by American College of Cardiology/American Heart Association clasification and Thrombolysis In Myocardial Infarction flow in two groups. 2) Angiographic restenosis rates were not different between two groups (group I : 33.8%, group II : 35.4%). CONCLUSION: Plasma Lp(a) levels are not related with the angiographic restenosis rate after coronary stent placement.
Apoprotein(a) ; Atherosclerosis ; Binding Sites ; Coronary Vessels ; Diagnosis ; Female ; Follow-Up Studies ; Heart ; Humans ; Jeollanam-do ; Lipoprotein(a)* ; Myocardial Infarction ; Plasma ; Plasminogen ; Plasminogen Activators ; Risk Factors ; Stents* ; Ventricular Function, Left

BACKGROUND/AIMS: Essential hypertension is the most common cardiovascular disease and is involved in the development of the various cardiac arrhythmias, including atrial fibrillation. Recently, several studies have shown that statins have anti-arrhythmic effects, including the prevention of atrial fibrillation. This study investigated the effects of statins on cardiac electrophysiologic remodeling in patients with essential hypertension using the signal-averaged electrocardiogram (ECG) and standard 12-lead ECG. METHODS: This prospective multicenter study enrolled 115 patients with hypertension. Various antihypertensive drugs were administered alone or in combination according to their blood pressure. Statins were administrated in 56 patients. Laboratory tests, a standard 12-lead ECG, and signal-averaged ECG were performed at 1, 3, 6, and 12 months. Statistical analysis was performed using paired and independent t-tests and repeated measures analysis of variance (ANOVA). RESULTS: There was no significant difference in the clinical characteristics of the patients with and without statins. After antihypertensive therapy for 1 year, the P wave dispersion, high-frequency low-amplitude (HFLA) signals in the QRS complex of less than 40 micronV, and T peak-to-end dispersion were increased significantly (p<0.001, p<0.05, and p<0.01, respectively) in the patients who were not taking statins, while these changes were not seen in the statin group. CONCLUSIONS: These results demonstrate that electrophysiologic remodeling was progressive in patients with essential hypertension, despite antihypertensive therapy. However, combination therapy with a statin may inhibit the deterioration of inhomogeneity in atrial refractoriness and conduction disturbance.
Antihypertensive Agents ; Arrhythmias, Cardiac ; Atrial Fibrillation ; Blood Pressure ; Cardiovascular Diseases ; Electrocardiography ; Electrophysiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypertension ; Prospective Studies