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Wolfgang Dichtl

Publications and source records attributed to Wolfgang Dichtl.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of three-dimensional imaging to transesophageal echocardiography for preoperative evaluation in mitral valve prolapse.

Transesophageal echocardiography (TEE) is not optimally suited for recognizing which valve segments are involved in type II mitral valve dysfunction. This study was conducted to compare the diagnostic value of TEE and 3-dimensional image reconstruction (3DIR) in the assessment of Carpentier type II mitral valve lesions. In 74 patients (mean age 59+/-13 years) with mitral regurgitation due to type II valve dysfunction, TEE and 3DIR were performed and analyzed by 2 experts before surgical repair. Leaflet scallops and commissures were displayed in short-axis en face and long-axis views. Echocardiographic results were surgically validated. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated, broken down by valve segments and Barlow's disease. Interobserver variability was also determined. Compared with TEE, 3DIR was superior with respect to sensitivity, positive and negative predictive values, and accuracy, although not always significantly (p<0.05). Specificity was higher for P2 lesions. The clearest advantage of 3DIR over TEE was higher sensitivity in commissural and bileaflet defects (p<0.05). Interobserver agreement on 3DIR was stronger than on TEE results (kappa values 0.52 vs 0.82, p<0.0001). There were 16 disagreements (23%) on TEE but only 5 (7%) on 3DIR readings. In conclusion, the more complex the lesion, the more valuable 3DIR is compared with TEE. Before repair, 3DIR is beneficial for the evaluation and classification of the specific pathology in type II mitral valve dysfunction.

Adult↗
PubMed2006

Multislice computed tomography for detection of patients with aortic valve stenosis and quantification of severity.

OBJECTIVES: The purpose of this study was to evaluate whether multislice computed tomography (MSCT) provides a reliable, noninvasive imaging modality for identification of patients with degenerative aortic valve stenosis (AS) by quantifying the aortic valve area (AVA) in comparison to the accepted diagnostic standard transthoracic echocardiography (TTE). BACKGROUND: Management of patients with degenerative AS is based on the severity of disease. The severity of AS in clinical practice is assessed by TTE and classified as mild, moderate, or severe according to the AVA. METHODS: Forty-six patients were examined with contrast-enhanced, electrocardiogram-gated, 16-row MSCT for the evaluation of the diagnostic accuracy. In 30 patients, quantification of the AVA with MSCT was compared to TTE using the continuity equation with Doppler velocity-time integral for calculation of the AVA. RESULTS: Sensitivity of MSCT for the identification of patients with degenerative AS was 100%, and the specificity was 93.7%. Thirty of 46 patients had AS determined by TTE. Quantification of AVA by MSCT (mean AVA = 0.94 cm2) in patients with AS showed a good correlation to TTE (r = 0.89; p < 0.001). Bland-Altman plot illustrated good intermodality agreement between the two methods (limits of agreement, 0.20; 0.29). CONCLUSIONS: Multislice computed tomography may provide an accurate, noninvasive imaging technique for detection of patients with AS and quantification of AVA.

Aged↗
PubMed2006

Acute motor and sensory axonal neuropathy in Burkitt-like lymphoma.

Immune-mediated neuropathies associated with non-Hodgkin's lymphoma are rare and can be difficult to delineate from neuropathies of other etiologies. We report the clinical and pathological findings of a 36-year-old patient with fulminant quadriplegic neuropathy, left facial nerve palsy, and Burkitt-like lymphoma. Features of the neuropathy, which occurred during induction chemotherapy with a total cumulative dose of 4 mg vincristine, suggested axonal Guillain-Barré syndrome. There was no evidence of direct malignant infiltration of the peripheral nervous system. We hypothesize that immune mechanisms triggered by the lymphoma initiated damage to the peripheral nervous system and enhanced its vulnerability to the toxic effects of vincristine.

Acute Disease↗
PubMed2006

Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease--a randomized, placebo-controlled study.

BACKGROUND: Coronary atherosclerosis includes an activation of circulating T lymphocytes. Statins exert anti-inflammatory effects beyond lipid lowering. Whether these properties influence systemic T lymphocytes is unclear. METHODS: To investigate the effect of atorvastatin on circulating T-lymphocyte subsets producing proinflammatory and anti-inflammatory cytokines (interferon gamma [IFN-gamma(+)], interleukin 2 [IL-2(+)], IL-4(+), and IL-10(+)) and on the T-cell-activating soluble CD40 ligand (sCD40L), 30 hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. Eight healthy volunteers served as controls. Levels of peripheral cytokine-producing CD4+ and CD8+ T cells and their CD28- subsets were determined by FACS. Serum soluble CD40L was measured with ELISA. RESULTS: IL-2(+) T lymphocytes and sCD40L levels were higher in patients with CAD compared with controls, whereas IFN-gamma(+) and anti-inflammatory IL-4(+) and IL-10(+) T lymphocytes were similar. Levels of IL-2(+), IFN-gamma(+), IL-4(+), and IL-10(+) T-cell subsets as well as CD28- T lymphocytes were neither changed by atorvastatin nor by placebo, whereas sCD40L was lowered only in atorvastatin-treated patients (P < .01). CONCLUSION: Circulating IL-2(+) T lymphocytes are increased in patients with stable CAD reflecting an activation of the global immune system, but are not influenced by atorvastatin therapy. The elevated levels of platelet-derived T-lymphocyte-stimulating sCD40L are decreased by atorvastatin probably reflecting an atheroprotective effect. Hence, sCD40L may be an additional biomarker to be considered when evaluating the treatment effects of statins in patients with stable CAD.

Atorvastatin↗
PubMed2006

Robotically assisted totally endoscopic atrial septal defect repair: insights from operative times, learning curves, and clinical outcome.

BACKGROUND: Remote access perfusion and robotics have enabled totally endoscopic closure of atrial septal defect and patent foramen ovale. The aim of this study was to address learning curve issues of totally endoscopic atrial septal defect repair on the basis of a single-center experience and to investigate whether long cardiopulmonary bypass and aortic occlusion times influence intraoperative and postoperative outcomes. METHODS: Seventeen patients (median age, 35 years; range, 16 to 55 years) underwent totally endoscopic atrial septal defect repair using remote access perfusion and robotic technology (da Vinci telemanipulation system). Learning curves were assessed by means of regression analysis with logarithmic curve fit. The effect of operative variables on clinical outcome was analyzed by linear regression using the Spearman's rho coefficient. RESULTS: No operative mortality or serious surgical complications were observed. No residual shunt was detected at intraoperative or postoperative echocardiography. Significant learning curves were noted for total operative time: y(min) = 406 - 49 ln(x) (r2 = 0.725; p = 0.002); cardiopulmonary bypass time: y(min) = 225 - 42 ln(x) (r2 = 0.699; p = 0.003); and aortic occlusion time: y(min) = 117 - 25 ln(x) (r2 = 0.517; p = 0.04), x = number of procedures. Median ventilation time, intensive care unit stay, and hospital length of stay were 7 hours (range, 2 to 19 hours), 26 hours (range, 15 to 120 hours), and 8 days (range, 5 to 14 days), respectively. No correlation was detected between cardiopulmonary bypass time and intubation time (r2 = 0.283; p = 0.326), intensive care unit stay (r2 = -0.138; p = 0.639), or total length of stay (r2 = 0.013; p = 0.962). CONCLUSIONS: Totally endoscopic atrial septal defect repair can be performed safely, and learning curves for operative times are steep. Longer cardiopulmonary bypass times had no negative impact on intraoperative and postoperative outcome.

Adolescent↗
PubMed2006

Diagnostic performance of MDCT for detecting aortic valve regurgitation.

OBJECTIVE: This study evaluates whether ECG-gated 16-MDCT coronary angiography provides a reliable imaging technique for detecting aortic regurgitation (AR). SUBJECTS AND METHODS: We examined 71 patients prospectively with 16-MDCT angiography using retrospective ECG gating during the mid-to-end diastolic phase. A visible central valvular leakage area was considered as a diagnostic criterion for AR. The central valvular leakage area was quantified in patients with positive transthoracic echocardiography (TTE). We compared 16-MDCT to Doppler TTE, the accepted diagnostic standard based on semiquantitative regurgitation jet analysis (grade 0-3+ for mild, moderate, and severe). RESULTS: The overall sensitivity of 16-MDCT for the identification of patients with AR was 81%. The specificity was 91%, the negative predictive value was 70%, and the positive predictive value was 95%. Of the 71 patients, 48 had AR determined by TTE, and 16-MDCT correctly detected AR in 39 of those 48 patients. The sensitivity of 16-MDCT for the detection of patients with moderate and severe AR (grade > or = 1.5+) was 95%, and the specificity was 96% (20 of 21 patients). The sensitivity of 16-MDCT for identification of patients with mild AR (grade < or = 1+) was 70%, and the specificity was 92% (19 of 27 patients). Quantification of the central valvular leakage area was not possible in 50% of cases with AR by TTE because of valve calcifications. CONCLUSION: Sixteen-MDCT coronary angiography provides an accurate, noninvasive imaging technique to detect moderate and severe aortic regurgitation (grade > or = 1.5+). However, severe valve calcifications and mild AR limit its results.

Adult↗
PubMed2006

Aortic valve calcification as quantified with multislice computed tomography predicts short-term clinical outcome in patients with asymptomatic aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Aortic valve calcification may be an independent risk factor for adverse clinical outcome. The study aim was to assess the predictive value of possible risk factors, including the severity of aortic valve calcification as quantified with 16-multislice computed tomography (MSCT) for adverse short-term clinical outcome in patients with asymptomatic, degenerative aortic stenosis (AS). METHODS: Possible risk factors for adverse short-term clinical outcome were prospectively tested in 34 consecutive patients with asymptomatic AS as follows: (i) aortic valve calcium (AVC) score as quantified with MSCT; (ii) echocardiographic parameters--aortic valve area (AVA) calculated with continuity equation, mean and maximal transvalvular pressure gradients, end-diastolic septal wall diameter; and (iii) laboratory tests (brain natriuretic peptide (BNP), C-reactive protein (CRP)). RESULTS: Within 18-24 months of follow up, 11 of 34 patients developed a major adverse clinical outcome. Ten patients suffered from onset of symptoms accompanied by hemodynamic progression, and one patient died from sudden cardiac death. Six of these 10 patients underwent aortic valve replacement, one patient declined surgery, and three patients were not accepted for surgery (one of these died suddenly shortly afterwards). The aortic valve calcium score was the strongest predictor of a major adverse clinical event (p < 0.001) among all parameters assessed (1,928 +/- 789 versus 5,111 +/- 2,409 Agatston units). The plasma level of BNP (p = 0.003), mean transvalvular pressure gradient (p = 0.002) and AVA (p = 0.003) were also risk factors for adverse clinical outcome. CONCLUSION: The AVC score as quantified with MSCT predicted adverse short-term clinical outcome in patients with asymptomatic AS. In patients with severe aortic valve calcification, close follow up examinations are mandatory, and early elective surgery may be considered even in the absence of symptoms. MSCT provides a comprehensive non-invasive imaging approach for risk stratification in patients with asymptomatic AS.

Aortic Valve↗
PubMed2005

Countervailing effects of rapamycin (sirolimus) on nuclear factor-kappa B activities in neointimal and medial smooth muscle cells.

OBJECTIVE: Local application of rapamycin (sirolimus) by drug-eluting stents prevents lumen obliteration after angioplasty by inhibition of neointimal hyperplasia. The effects of rapamycin on neointimal smooth muscle cells (niSMC) which are responsible for the occurrence of restenosis have not been investigated so far. METHODS AND RESULTS: Rat niSMC and medial SMC (mSMC) were obtained from balloon catheter-injured arteries. The niSMC exhibited higher basal NF-kappaB activity and TNF-alpha mRNA levels. Nuclear protein binding to NF-kappaB-DNA was attenuated in niSMC by incubation with rapamycin (0.1 and 1 microg/ml) for 24 and 48 h. In contrast in mSMC, 0.1 microg/ml rapamycin had no effect and at 1 microg/ml even increased nuclear protein binding to NF-kappaB-DNA. After 12 h incubation, rapamycin (0.001-10 microg/ml) induced IkappaB-alpha protein in niSMC, whereas in mSMC it stimulated IkappaB-alpha at much lower levels. Prolonged rapamycin treatment (1 microg/ml for 72 h) had no effect on TNF-alpha mRNA level and NF-kappaB activity in niSMC, whereas it led to their increase in mSMC. Vascular endothelial growth factor (VEGF) secretion was higher in mSMC than in niSMC; rapamycin decreased VEGF levels in both cell types. Ultrastructural analysis suggested that rapamycin caused early signs of degeneration in niSMC, but enhanced protein synthesis in mSMC. CONCLUSIONS: This study shows that rapamycin influences the inflammatory phenotypes of SMC in opposite directions: it reduces the high basal NF-kappaB activity in niSMC and enhances NF-kappaB activity and TNF-alpha expression in mSMC. In addition, rapamycin inhibits VEGF production regardless of the phenotype of SMC. These findings shed light on molecular mechanisms and structural changes underlying therapeutic applications of rapamycin in prevention of restenosis, inhibition of chronic transplant arteriosclerosis and reduction of secondary malignoma formation due to immunosuppression.

Animals↗
PubMed2005

Prognostic value of brachial artery endothelial function and wall thickness.

OBJECTIVES: We sought to examine the prognostic value of brachial artery (BA) flow-mediated vasodilation (FMD) and intima-media thickness (IMT) in patients admitted for invasive evaluation of chest pain. BACKGROUND: Both FMD and IMT of the BA have been associated with coronary risk factors and the presence of coronary artery disease (CAD). Recent studies on the prognostic value of FMD have been conflicting. METHODS: In 398 consecutive patients (age 54 +/- 9 years) undergoing coronary angiography, FMD and IMT of the BA were measured using high-resolution ultrasound (13 MHz). Patients were divided into two groups according to the FMD median (7.6%). After a mean follow-up of 39 +/- 12 months, cardiovascular events were documented. RESULTS: No difference was found in the number of cardiovascular events between groups. On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of CAD, FMD, and IMT, only the presence of CAD and IMT remained significantly associated with cardiovascular events. CONCLUSIONS: Intima-media thickness predicted late (up to 4 years) cardiovascular events in a large population admitted for evaluation of chest pain. In contrast, the long-term prognostic value of a single baseline measure of BA-FMD seems to be limited.

Adult↗
PubMed2005

Very low density lipoprotein potentiates tumor necrosis factor-alpha expression in macrophages.

High levels of the triacylglycerol-rich lipoproteins, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) have been identified as independent risk factors for coronary heart disease, and inflammation is thought to contribute to atherosclerosis and its complications. To understand how dyslipidemia promotes inflammation, we have characterised the effects of VLDL treatment on production of tumor necrosis factor-alpha (TNF) by human monocyte-derived macrophages. VLDL strongly potentiated lipopolysaccharide (LPS)-induced expression of TNF mRNA and secretion of TNF protein. VLDL activated mitogen-activated protein kinase-ERK kinase 1/2 (MEK1/2), and potentiated LPS-induced MEK1/2 activation. The MEK1/2 inhibitor U0126 strongly diminished TNF expression, indicating that MEK1/2 plays a central role in the regulation of TNF expression. VLDL did not activate transcription factors NF-kappaB and PPAR-gamma, but it activated AP-1 at least as potently as LPS, and potentiated LPS-induced activation of AP-1. The inhibitor U0126 completely prevented this potentiation. Inhibition of AP-1 by decoy oligonucleotides abolished potentiation of TNF secretion by VLDL. In conclusion, VLDL treatment potentiates TNF expression in macrophages by activation of MEK1/2 and AP-1. These findings suggest that triacylglycerol-rich lipoproteins are involved in inflammatory processes associated with atherosclerosis.

Arteriosclerosis↗
PubMed2005

An uncommon coronary artery fistula causing survived sudden cardiac death in a young woman.

Although most patients suffering from a coronary artery fistula remain asymptomatic during childhood and adolescence, many of them develop complications in adulthood due to volume overload, endocarditis or ischemia. Here we present a young woman surviving a sudden cardiac death due to myocardial ischemia with subsequent ventricular fibrillation caused by thrombosis of a coronary artery fistula deriving from the left main coronary artery. Parts of the thrombus had been embolized into the circumflex artery causing posterior myocardial infarction. The thrombosis might have been initiated by local compression from a round extracardiac mass of 3 cm with liquid and solid content located between the vena cava superior and the ascending aorta. This structure was suspected to be a hematoma which had been caused by a blunt thoracic trauma while playing soccer 2 weeks before.

Adult↗
PubMed2005

Cardiac hepatopathy before and after heart transplantation.

Chronic cardiac hepatopathy is a common entity in patients evaluated for heart transplantation (HTX). Hepatic injury is caused by severe heart failure resulting from prolonged recurrent congestion and/or impaired arterial perfusion. No data are available on the reversibility of cardiac hepatopathy in patients undergoing HTX. Data of 56 consecutive adult patients undergoing HTX during 2000-02 at the University Hospital of Innsbruck were analysed retrospectively. The following parameters were evaluated at the time of listing and 3, 6 and 12 months after HTX. Plasma levels of gamma-glutamyl transferase (gamma-GT), alkaline phosphatase (AP), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and total plasma protein. When listed for HTX, only 12% of all patients analysed had physiological values throughout the seven laboratory parameters assessed. Elevated levels of gamma-GT, AP, bilirubin, AST, ALT, LDH and total plasma protein were detected in 66.6%, 29%, 50%, 16.7%, 10%, 40% and 18% of all patients respectively. Accordingly, median plasma levels of gamma-GT, bilirubin and LDH were elevated, whereas the mean plasma level of AP was at the upper normal range. In contrast, median plasma level of AST and mean plasma levels of ALT and total plasma protein were within the normal range: gamma-GT (median, 109.0; range, 634.0 U/l; n = 36), AP (mean, 120.2 +/- 78.9 U/l; n = 29), bilirubin (median, 1.3; range, 16.1 mg/dl; n = 32), LDH (median, 226.0; range, 2355.0 U/l; n = 33), AST (median, 29.0; range, 145.0 U/l; n = 36), ALT (mean, 28.3 +/- 20.8 U/l; n = 36) and total plasma protein (mean, 7.2 +/- 1.1 g/dl; n = 25). Within 3 months after HTX, elevated parameters except LDH significantly ameliorated: gamma-GT (median, 59.0; range, 1160.0 U/l; P = 0.011), AP (92.2 +/- 75.2 U/l; P = 0.016), bilirubin (median, 0.9; range, 8.1 mg/dl; P = 0.004), LDH slightly increased (median, 281.0; range, 543.0 U/l; P = 0.039), but there was a delayed improvement of this parameter after 6 and 12 months post-HTX. End-stage heart failure is characterized by a cholestatic liver enzyme profile with elevated plasma levels of gamma-GT and bilirubin. These parameters significantly improve within 3 months after HTX. Therefore, chronic cardiac hepatopathy seems to be a benign, potentially reversible disease.

Alanine Transaminase↗
PubMed2005

High-resolution 16-MDCT evaluation of radial artery for potential use as coronary artery bypass graft: a feasibility study.

OBJECTIVE: The objective of our study was to assess the feasibility of using 16-MDCT angiography for the preoperative assessment of the radial and ulnar arteries and the palmar arches in patients scheduled for radial artery harvesting for coronary artery bypass graft (CABG) surgery. CONCLUSION: Sixteen-MDCT angiography shows promise for the noninvasive preoperative assessment of the radial artery as a CABG donor site.

Aged↗
PubMed2004

C-reactive protein plasma levels but not factor VII activity predict clinical outcome in patients undergoing elective coronary intervention.

BACKGROUND: Both vascular inflammation as determined by C-reactive protein (CRP) and extrinsic coagulation as measured by factor VII activity (F VII) may predict clinical restenosis rate in patients with stable angina pectoris undergoing elective percutaneous coronary intervention (PCI). HYPOTHESIS: The primary objective of this study was to investigate the associations between baseline CRP levels, F VII activity, and restenosis rate after elective PCI in a 6-month follow-up period. METHODS: This prospective study included 81 patients aged > or = 19 years undergoing PCI for angiographically significant (> or = 70%) stenosis, with or without stenting, and 49 controls. Factor VII activity and CRP were measured in samples collected at angiography and 16-24 h post procedure after overnight fast. Successful PCI was defined as final diameter of < 50% with TIMI 3 flow and no complication within 1 h. After 6 months all patients who had undergone PCI were evaluated via a standardized questionnaire. Clinical restenosis was defined as the occurrence of a major adverse coronary events (MACE), within the follow-up period. RESULTS: Diagnostic angiography led to a significant increase in CRP levels after 16-20 h in patients with discrete CAD (n = 22) but not in patients without any signs of coronary atherosclerosis (n = 27). During a 6-month follow-up after PCI, 17 of 81 (21%) patients developed MACE. Tertiles of CRP levels independently predicted clinical restenosis, as it developed in 33.3% of patients with the highest CRP levels (0.7-4.8 mg/dl), in 16.6% of patients with second tertile CRP levels (0.23-0.69 mg/dl), and in 7.4% of patients with lowest tertile CRP levels (0.0-0.22 mg/dl). There was a significant difference in the restenosis rate between patients from the first and the third tertiles (p = 0.018). Successful PCI was associated with a significant decrease of mean CRP levels after 6 months, whereas PCI in patients suffering from MACE led to no change in CRP levels. There was no association between factor VII activity and clinical outcome after PCI, and F VII activity did not change over a 6-month period. CONCLUSIONS: In patients with stable angina pectoris undergoing elective PCI, increased preprocedural and 6-month follow-up CRP plasma levels are associated with clinical restenosis. Factor VII plasma activity lacks such correlations.

Adult↗
PubMed2003

HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells.

OBJECTIVE: Pleiotropic atheroprotective effects of HMG-CoA reductase inhibitors may be mediated on the level of vascular gene transcription. The aim of this study was to characterize the effects of statins on the activation of transcription factors known to regulate inflammation and cell proliferation/differentiation. METHODS AND RESULTS: Simvastatin, atorvastatin, and lovastatin (0.1 to 10 micro mol/L) inhibited the binding of nuclear proteins to both the nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) DNA consensus oligonucleotides in human endothelial and vascular smooth muscle cells as assessed by electrophoretic mobility shift assay (EMSA). The inhibitory effects of statins on NF-kappaB or AP-1-dependent transcriptional activity were examined by transient transfection studies. HMG-CoA reductase inhibitors upregulated IkappaB-alpha protein levels in endothelial cells and decreased c-Jun mRNA expression in smooth muscle cells as analyzed by Western and Northern blotting, respectively. Furthermore, statins inhibited DNA binding of hypoxia-inducible factor-1alpha. Downstream effects of statins included inhibition of plasminogen activator inhibitor-1 and vascular endothelial growth factor-A mRNA levels in endothelial cells. CONCLUSIONS: HMG-CoA reductase inhibitors downregulate the activation of transcription factors NF-kappaB, AP-1, and hypoxia-inducible factor-1alpha. These findings support the concept that statins have antiinflammatory and antiproliferative effects that are relevant in the treatment of atherosclerotic diseases.

Atorvastatin↗
PubMed2003

Statins differentially regulate vascular endothelial growth factor synthesis in endothelial and vascular smooth muscle cells.

OBJECTIVES: HMG-CoA reductase inhibitors (statins) can modulate the formation of new blood vessels, but the reports on their contribution to angiogenesis are contradictory. Therefore, we investigated whether the effect of statins is dependent either on the concentration of the drug or on the cell type. METHODS AND RESULTS: Under basal conditions human vascular smooth muscle cells (HVSMC) and microvascular endothelial cells (HMEC-1) constitutively generate and release vascular endothelial growth factor (VEGF). In contrast, primary macrovascular endothelial cells (HUVEC) produce minute amounts of VEGF. Different statins (atorvastatin, simvastatin and lovastatin, 1-10 micromol/l) significantly reduced basal and cytokine-, nitric oxide- or lysophosphatidylcholine (LPC)-induced VEGF synthesis in HMEC-1 and HVSMC. Interestingly, at the same concentrations statins upregulated VEGF generation in HUVEC. Furthermore, statins exerted dual, concentration-dependent influence on angiogenic activities of HUVEC as determined by tube formation assay. At low concentrations (0.03-1 micromol/l) the pro-angiogenic activity of statins is prevalent, whereas at higher concentrations statins inhibit angiogenesis, despite increasing VEGF synthesis. CONCLUSION: Our data show that statins exert concentration- and cell type-dependent effects on angiogenic activity of endothelial cells and on VEGF synthesis. The data are of relevance for elucidating the differential activity of statins on angiogenesis in cardiovascular diseases and cancer.

Atorvastatin↗