Phosphorylation of the endothelial nitric oxide synthase at Ser-1177 is required for VEGF-induced endothelial cell migration

AbstractVascular endothelial growth factor (VEGF) stimulates endothelial cell (EC) migration. The protein kinase Akt activates the endothelial NO synthase (eNOS) by phosphorylation of Ser-1177. Therefore, we investigated the contribution of Akt-mediated eNOS phosphorylation to VEGF-induced EC migration. Inhibition of NO synthase or overexpression of a dominant negative Akt abrogated VEGF-induced cell migration. In contrast, overexpression of constitutively active Akt was sufficient to induce cell migration. Moreover, transfection of an Akt site phospho-mimetic eNOS (S1177D) potently stimulated EC migration, whereas a non-phosphorylatable mutant (S1177A) inhibited VEGF-induced EC migration. Our data indicate that eNOS activation via phosphorylation of Ser-1177 by Akt is necessary and sufficient for VEGF-mediated EC migration

Interventional cardiology in Europe 1999

Aims The purpose of this registry is to collect data on trends in interventional cardiology within Europe. Special interest focuses on relative increases and ratios in newer revascularization approaches and its distribution in different regions in Europe. Methods and Results Questionnaires distributed to delegates of the national societies of cardiology represented in the European Society of Cardiology to be completed by local institutions and operators yielded that 1 452 751 angiograms and 452 019 PTCAs were performed in 1999. This is an increase of 28% and 16%, respectively, compared with 1998. Most of these increases are due to high relative increases in eastern European countries. The number of PTCAs per 106 inhabitants rose to 714 in 1999. Coronary stenting increased by 31% to about 313 000 stents implanted in 1999. Complication rates remained stable, the need for emergency coronary artery bypass grafting showing a further slight decrease to currently 0.3%. Conclusion Interventional cardiology in Europe is still growing, mainly due to rapid growth in countries with lower socio-economical levels. In some central European countries a saturation seemed to be reached with only minor increases in procedures performed. Coronary stenting remains the only noteworthy and growing complement or alternative to balloon angioplast

Coronary vasomotion in response to sympathetic stimulation in humans: Importance of the functional integrity of the endothelium

AbstractThe coronary vasomotor response to the cold pressor test was studied with use of quantitative coronary angiography in 32 patients without evidence of coronary artery disease and 55 patients with such disease; in a subset of 22 patients (9 with normal coronary arteries and 13 with coronary artery disease), the effects of the cold pressor test were compared with the effects of the endothelium-dependent vasodilator acetylcholine with simultaneous intracoronary Doppler flow velocity measurements to assess the influence of endothelial dysfunction. The cold pressor test induced vasodilation of 8.9 ± 5.7% in all 77 analyzed vessel segments of the group with normal arteries (p < 0.01). In contrast, in patients with coronary artery disease, the 52 analyzed stenotic segments were constricted by −12.1 ± 9.5% (p < 0.01), the 57 analyzed vessel segments with luminal irregularities were constricted by −8.9 ± 5.2% (p < 0.01) and 40 (85%) of 47 angiographically normal segments also were constricted by −7.0 ± 4.9% (p < 0.05).Preserved vasodilating capability was demonstrated by intracoronary nitroglycerin in all analyzed segments. In nine patients with normal coronary arteries, the analyzed vessel segments were dilated in response to both the cold pressor test and intracoronary acetylcholine by 10.9 ± 5.4% and 13.4 ± 4.7%, respectively. In contrast, in all 13 patients with coronary artery disease, vasoconstriction of identical vessel segments by −9.1 ± 3.75% and −23 ± 10.4%, respectively, was observed after both the cold pressor test and intracoronary acetylcholine. Intracoronary propranolol did not significantly affect either the vasodilative response in 11 normal coronary arteries (11.3 ± 4.4% before and 8.6 ± 4.3% after beta-blockade) or the vasoconstrictor response in 8 atherosclerotic coronary arteries (−11.4 ± 4.6% before and −14.6 ± 5.3% after betablockade).The dilation of normal and the constriction of atherosclerotic coronary arteries with cold pressor testing exactly mirror the response to the endothelium-dependent dilator acetylcholine. Endothelial dysfunction in coronary atherosclerosis resulted in a loss of normal dilator function and permitted vasoconstrictor responses to sympathetic stimulation. Thus, coronary vasomotion of large epicardial arteries in response to sympathetic stimulation by the cold pressor test in humans is intimately related to the integrity of endothelial function

Percutaneous coronary interventions in Europe 1992-2001

Aims The purpose of this registry is to collect data on trends in interventional cardiology within Europe. Special interest focuses on relative increases and ratios in newer re-vascularisation approaches and its distribution in different regions in Europe. We report the data of the year 2001 and give an overview of the development of coronary interventions since 1992, when the first data collection was performed. Methods and Results Questionnaires were distributed to delegates of the individual national societies of cardiology represented in the European Society of Cardiology. These were completed by the local institutions and operators and showed that 1,806,238 angiograms and 617,176 percutaneous transluminal coronary angioplasties (PTCAs) were performed in 2001. This is an increase of 10% and 17%, respectively, compared with the year 2000. The population-adjusted PTCA rate rose from nearly 800 procedures per 106 inhabitants in the year 2000 to approximately 990 procedures per 106 inhabitants in 2001. Coronary stenting increased by 25% to about 488,900 stents implanted in 2001. Complication rates remained unchanged, and the need for emergency coronary artery bypass grafting is still at 0.2% per percutaneous intervention. Conclusion Interventional cardiology in Europe is still expanding, mainly due to rapid growth in countries with lower socio-economical levels. Most central European countries reported only minor increases in procedures performed. Coronary stenting remains the only noteworthy adjunctive strategy to balloon angioplast

Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes Comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis

ObjectivesThe goal of this study was to determine the predictive value of pregnancy-associated plasma protein-A (PAPP-A) in patients with acute coronary syndromes (ACS).BackgroundPregnancy-associated plasma protein-A is a zinc-binding matrix metalloproteinase abundantly expressed in eroded and ruptured plaques and may serve as a marker of plaque destabilization.MethodsIn 547 patients with angiographically validated ACS and in a heterogeneous emergency room population of 644 patients with acute chest pain, respectively, PAPP-A as well as markers of myocardial necrosis (troponin T [TnT]), ischemia (vascular endothelial growth factor [VEGF]), inflammation (high-sensitivity C-reactive protein [hsCRP]), anti-inflammatory activity (interleukin [IL]-10), and platelet activation (soluble CD40 ligand [sCD40L]) were determined. Patients were followed for the occurrence of death or myocardial infarction.ResultsIn patients with ACS, elevated PAPP-A levels (>12.6 mIU/l) indicated an increased risk (odds ratio 2.44 [95% confidence interval (CI) 1.43 to 4.15]; p = 0.001). When the analysis was restricted to TnT-negative patients, PAPP-A still identified a subgroup of high-risk patients (odds ratio [OR] 2.72 [95% confidence interval (CI) 1.25 to 5.89]; p = 0.009). In a multivariable model, PAPP-A (OR 2.01; p = 0.015), sCD40L (OR 2.37; p = 0.003), IL-10 (OR 0.43; p = 0.003), and VEGF (OR 2.19; p = 0.018) were independent predictors. Prospective validation in patients with chest pain confirmed that PAPP-A levels reliably identify high-risk patients (adjusted OR 2.32 [95% CI 1.32 to 4.26]; p = 0.008). Patients negative for all three markers (TnT, sCD40L, and PAPP-A) were at very low cardiac risk (30 days: 3.0% event rate; no death).ConclusionsThe PAPP-A level as a marker of plaque instability is a strong independent predictor of cardiovascular events in patients with ACS. Simultaneous determination of biomarkers with distinct pathophysiological profiles appears to remarkably improve risk stratification in patients with ACS

Nutritional risk index is a better predictor of early mortality than conventional nutritional markers after transcatheter aortic valve replacement: A prospective cohort study

Background: Nutritional risk index (NRI) has been shown to better predict survival than body mass index (BMI) or albumin after several cardiovascular interventions. Under assessment herein is whether NRI can have higher predictive value than conventional parameters for short-term survival after transcatheter aortic valve replacement (TAVR).Methods: A prospective cohort study was performed. In-hospital, 1-month and 3-month survival was evaluated. Since most patients undergoing TAVR are over 65, the NRI definition for a geriatric population (GNRI) was used. The impact of baseline BMI, albumin levels, and GNRI on in-hospital and short-term survival was assessed.Results: One hundred fifty two patients aged 82 ± 5.4 were included. In-hospital, 1-month, and 3-month mortality was 5.3%, 5.9%, and 9.2%, respectively. Mean GNRI was 112.7 ± 11.9, and was significantly lower in patients who died in-hospital (101.0 ± 8.8 vs. 113.3 ± 11.7), at 30 days (103.4 ± 10.9 vs. 113.3 ± 11.7), and at 90 days (104.0 ± 9.6 vs. 113.6 ± 11.8) than in survivors (all, p &lt; 0.05). Three-month mortality in patients with no nutritional risk was 6.8% (9/132) vs. 25% (5/20) in patients with malnutrition (p = 0.022). In univariate analysis, GNRI predicted in-hospital, 30-day, and 90-day mortality (all, p &lt; 0.05). Predictive value remained significant after adjusting for age, EuroSCORE II, and STS-Score (p &lt; 0.05). Based on receiver operating curves, GNRI (AUC: 0.73) showed a betterdiscrimination for 3-month mortality than albumin (0.69), weight (0.67) or BMI (0.62). The optimal cut-off value was 109.8.Conclusions: The geriatric nutritional risk index predicts short-term mortality after TAVR and has a higher discriminating ability than other commonly used nutritional variables. It is a simple parameter that identifies those patients who could benefit from pre-procedural nutritional therapy