The inhibition of insulin-stimulated proliferation of vascular smooth muscle cells by rosiglitazone is mediated by the Akt-mTOR-P70S6K pathway

PURPOSE: Thiazolidinediones (TZDs) are known to inhibit the proliferation of vascular smooth muscle cell (VSMC) by increasing the activity of p27(Kip1) and retinoblastoma protein (RB). However, the upstream signaling mechanisms associated with this pathway have not been elucidated. The Akt-mTOR-P70S6 kinase pathway is the central regulator of cell growth and proliferation, and increases cell proliferation by inhibiting the activities of p27(Kip1) and retinoblastoma protein (RB). Therefore, we hypothesized in this study that rosiglitazone inhibits VSMC proliferation through the inhibition of the Akt-TOR-P70S6K signaling pathway. MATERIALS and METHODS: Rat aortic smooth muscle cells (RAoSMCs) were treated with 10microM of rosiglitazone 24 hours before the addition of insulin as a mitogenic stimulus. Western blot analysis was performed to determine the inhibitory effect of rosiglitazone treatment on the Akt-mTOR-P70S6K signaling pathway. Carotid balloon injury was also performed in Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats that were pretreated with 3 mg/kg of rosiglitazone. RESULTS: Western blot analysis demonstrated significant inhibition of activation of p-Akt, p-m-TOR, and p-p70S6K in cells treated with rosiglitazone. The inhibition of the activation of the p-mTOR-p-p70S6K pathway seemed to be mediated by both the upstream PI3K pathway and MEK-ERK complex. CONCLUSION: The inhibitory effect of rosiglitazone on RAoSMC proliferation in vitro and in vivo is mediated by the inhibition of the Akt-mTOR-P70S6K pathway.ope

Pulsed Wave and Color Doppler Echocardiography and Cardiac Catheterizatibn Findings in Bilateral Pulmonary Vein Stenosis

Pulmonary vein stenosis is a rare condition which is usually congenital in origin and is almost invariably fatal in its bilateral and severe forms. It is often overlooked, however, during clinical examination, routine echocardiography, and even at cardiac catheterization. This report describes pulsed Doppler, color flow echocardiography, and hemodynamic findings of bilateral pulmonary vein stenosis accompanying ventricular septal and atrial septal defects successfully corrected by surgery.ope

The Effect of Plant Sterol on Serum Cholesterol in Hypercholesterolemia Patients

Background and Objectives：Phytosterols (Plant sterols) have been known to reduce serum cholesterol concentrations by inhibiting the absorption of both dietary and biliary cholesterol from the small intestines. In consideration of the lack of evaluation in Korea into the hypercholesterolemic effect of plant sterols, this study investigated the effect of plant sterol containing beverage on blood lipid profiles in hypercholesterolemic patients. Materials and Method：Forty-five hypercholesterolemic patients (fasting LDL-cholesterol\>130 mg/ dL) were fed either a placebo beverage for 4 weeks or a test beverage containing plant sterols for 8 weeks in a single-blind, randomized, cross-over study. The subjects were instructed to maintain the same amount of dietary fat and cholesterol intake during the study. After 4 weeks of plant sterols treatment, the dose of plant sterols was doubled (3.2 g/d) for subjects whose LDL-cholesterol reduction rate had not been reduced by 15%. Results：The study population consisted of 45 patients (15 males, 30 females, mean age 56) who completed the whole protocol. At baseline, the subjects’ mean dietary intake of saturated fat was 11.12 g, and cholesterol was 135.2 mg. After 8 weeks of treatment with plant sterols, serum concentrations of total cholesterol and LDL-cholesterol were significantly reduced by 4.38% (p＝0.039), and 8.28% (p＝0.036), respectively. However, the HDL-cholesterol and triglyceride levels/concentrations did not change significantly. Two-thirds of the subjects responded to treatment with plant sterols, and the mean reduction rates in LDL-cholesterol and total cholesterol levels/concentrations of those subjects were 14.1% and 9.2%, respectively. Conclusion：Our findings indicate that plant sterols significantly reduce serum total cholesterol and LDL-cholesterol concentrations and further suggest that plant sterols are also effective for those with low cholesterol intake.ope

Triphasic mitral inflow velocity with mid-diastolic flow: The presence of mid-diastolic mitral annular velocity indicates advanced diastolic dysfunction

Mitral inflow filling pattern usually consists of 2 forward flow velocities in sinus rhythm: early rapid filling (E) and late filling with atrial contraction (A). However, additional mid-diastolic flow velocity may be present resulting in triphasic mitral inflow filling pattern. When mitral inflow is triphasic, mitral annulus velocity recorded by tissue Doppler imaging (TDI) frequently demonstrates a mid-diastolic component (L′). The significance of L′ has not been explored previously. The purpose of this study was to explore possible mechanisms and clinical implications of triphasic mitral inflow with or without L′ using TDI and proBNP. Of 9004 patients who underwent transthoracic echocardiography from March to November 2003, 83 (0.9%) patients (33 male, 50 female; mean age, 63±10 years) with a triphasic mitral inflow velocity pattern, including mid-diastolic flow velocity of at least 0.2m/s, and sinus rhythm were prospectively identified in our clinical echocardiography laboratory. Peak velocity of E, mid-diastolic (L), and A, and deceleration time (DT) of the E wave velocity were measured. Diastolic mitral annular velocities were measured at the septal corner of the mitral annulus by TDI from the apical 4-chamber view. ProBNP was measured at the time of echocardiogram using a quantitative electrochemiluminescence immunoassay. Mean heart rate was 54±6beats/min (range, 40–67). Mean left ventricular (LV) ejection fraction (EF) was 64±13% and LV systolic dysfunction (EF<40%) was present in only 6 (7%). Patients were classified into 2 groups: group 1 (n=47) included those who had L′ and group 2 (n=36) included those without L′. Group 1 patients had significantly higher peak velocity (35±14 vs 26±6cm/s, p=0.0002) and TVI (35±14 vs 26±6cm/s, p=0.0002) of L, E/E′ (18±8 vs 14±6, p=0.02), and left atrial volume index (42±14 vs 34±10ml/m2, p=0.0037). E′ (4.7±1.3 vs 6.2±2.3cm/s, p=0.001) and A′ (6.2±2.0 vs 8.6±3.4cm/s, p=0.0006) were significantly lower in group 1 compared with those of group 2. ProBNP was significantly higher in group 1 (847±1461 vs 438±1039pmol/l, p=0.0012) and it was above normal in all except in 1 patient of group 1. In conclusion, the presence of L′ in subjects with triphasic mitral inflow velocity pattern with mid-diastolic flow is associated with higher E/E′, elevated proBNP and enlarged left atrium indicating advanced diastolic dysfunction with elevated filling pressures. This unique mitral annular velocity pattern should be helpful in identifying the patients with advanced diastolic dysfunction and increased LV filling pressures.ope

Constrictive epicarditis as an unusual cause of constrictive physiology: typical presentation with unusual pathology

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The Relationship between Q-wave Regression and Improvement in the Left Ventricular Systolic Function after an Anterior Wall Acute Myocardial Infarction

Background and Objectives：An abnormal Q wave, after an acute myocardial infarction, has been considered an indicator of myocardial necrosis. However, in some cases this Q wave partially or completely disappears during the evolution of the myocardial infarction. The clinical significance of Q wave regression remains to be established. Accordingly, this study was conducted to evaluate the relationship between Q wave regression, after an anterior wall acute myocardial infarction, and the improvements of the regional wall motion abnormality and left ventricular ejection fraction in echocardiography. Subjcets and Methods：A total of 80 patients, who presented with a first anterior wall acute myocardial infarction, managed successfully with direct intervention, were divided into two groups according to the regression (group A) or presence (group B) of abnormal Q waves. Regression of an abnormal Q wave was defined as the disappearance of the Q wave and reappearance of the R wave ≥0.1 mV, in at least two of the I, aVL, and V1 to V6 leads. Results：Of the 80 patients, 26 (32.5 %) had an abnormal Q wave regression within 12 months. The peak creatine kinase-MB activity was lower in group A than B (277.3±202.6 vs. 521.3±284.4 ng/dL, p<0.01). Group A had better left ventricular regional wall motion than group B in the initial echocardiograms. The degree of improvement of the left ventricular ejection fraction and regional wall motion between the initial and follow-up echocardiographies were significantly greater in group A than B. Conclusion：Patients with an anterior wall acute myocardial infarction, showing Q wave regression, tended towards a smaller amount of necrotic myocardium and a significantly larger amount of stunned myocardium.ope

Uncommon variation in the papillary muscles presenting with ST elevation and T-wave inversion

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Atherosclerotic Obstruction of Lower Limb Arteries in Diabetic Foot: Effectiveness of Percutaneous Intervention

Background and Objectives：Peripheral arterial disease is a risk factor for foot ulcers and amputation in diabetic patients. Percutaneous intervention of an obstructed lower limb artery is one of the treatments for diabetic foot；however, few data are available on this treatment and its effectiveness. The aim of this study was to investigate atherosclerotic obstruction in lower limb arteries and to evaluate the feasibility and effectiveness of percutaneous intervention in salvaging a lower limb with diabetic foot. Subjects and Methods：Fifty-two consecutive subjects (mean age：64) with diabetic foot underwent angiography of the lower limbs. In patients with significant narrowing (diameter stenosis >50%), percutaneous intervention was performed. Angiographic success was defined as restoration of distal blood flow with residual stenosis less than 30%. During follow-up, bypass surgery was performed when clinically indicated in some patients and the state of diabetic foot was evaluated. Results：Forty-nine patients (94%) showed atherosclerotic narrowings in lower limb arteries and 34 of them (65%) had significant lesions. Among those 34 subjects, interventions were carried out in 30 cases (balloon angioplasty in 11, stenting in 18, and intra-arterial thrombolytic therapy in 1). In the other 15, intervention was not indicated. Twenty-six (86%) of the 30 procedures were angiographically successful. During the follow-up (7±6 months), 12 subjects (57%) experienced wound healing with or without forefoot amputation or bypass surgery, whereas 3 had major amputation. Four patients died during the period. Conclusion：The majority of patients with diabetic foot had atherosclerotic obstruction in lower limb arteries. Percutaneous intervention may salvage limbs and reduce the rate of major amputation in patients with diabetic foot.ope

The Prognostic Significance of ST Segment Depression Score in Acute Non ST Elevation Myocardial Infarction

Background and Objectives：A significant ST segment depression is known to be an independent risk factor for acute coronary syndrome (ACS). Defining high risk groups in non ST elevation myocardial infarction (NSTEMI) is especially important due the poor long term prognosis of these patients. The purpose of this study was to determine the prognostic significance of the degree of ST depression on admission, as determined by a novel ST depression scoring system. Subjects and Methods：68 patients, admitted to Yonsei Cardiovascular Hospital between Jan 2001 and Aug 2002, and diagnosed with acute non ST elevation myocardial infarction were included in this study. Analysis of the initial ECG on admission was retrospectively performed. Results：ST depression scores ≥1 and <1 were present in 36 (Group I) and 32 (Group II) patients, respectively. The rate of multivessel disease was significantly higher in group I than II (76.7 vs. 50%, p=0.032), the use of glycoprotein IIb/IIIa inhibitors was more frequent in group I than II (25 vs. 6.3%, p=0.041) and the left ventricular ejection fraction was significantly lower in group I than II (44.6±14.5 vs. 54.5±11.6%, p<0.05). The one-year survival rates were 68.9 and 93.7% for Groups I and II, respectively; p=0.0095), with Group I having a significantly higher early in-hospital mortality rate compared to group II.( 27.8 vs. 3.1%, p=0.0058) The event free survival rate in group I was lower than that in group II (55 vs. 90.6%, p=0.001). Conclusion：The ST depression score may be useful as an objective prognostic factor in acute NSTEMI, which may be especially useful for prediction of the early in hospital prognosis.ope

Pulmonary Arteriovenous Malformations

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