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BACKGROUND AND PURPOSE Pathological angiogenesis is associated with various human diseases, such as cancer, autoimmune diseases and retinopathy. The angiopoietin (Ang)-Tie2 system plays critical roles in several steps of angiogenic remodelling. Here, we have investigated the anti-angiogenic effect of a novel angiopoietin-derived peptide. EXPERIMENTAL APPROACH Using computational methods, we identified peptides from helical segments within angiopoietins, which were predicted to inhibit their activity. These peptides were tested using biochemical methods and models of angiogenesis. The peptide with best efficacy, A11, was selected for further characterization as an anti-angiogenic compound. KEY RESULTS The potent anti-angiogenic activity of A11 was demonstrated in a multicellular assay of angiogenesis and in the chorioallantoic membrane model. A11 bound to angiopoietins and reduced the binding of Ang-2 to Tie2. A11 was also significantly reduced vascular density in a model of tumour-induced angiogenesis. Its ability to inhibit Ang-2 but not Ang-1-induced endothelial cell migration, and to down-regulate Tie2 levels in tumour microvessels, suggests that A11 targets the Ang-Tie2 pathway. In a rat model of oxygen-induced retinopathy, A11 strongly inhibited retinal angiogenesis. Moreover, combination of A11 with an anti-VEGF antibody showed a trend for further inhibition of angiogenesis, suggesting an additive effect. CONCLUSIONS AND IMPLICATIONS Our results indicate that A11 is a potent anti-angiogenic compound, through modulation of the Ang-Tie2 system, underlining its potential as a therapeutic agent for the treatment of ocular and tumour neovascularization, as well as other pathological conditions that are dependent on angiogenesis. [ABSTRACT FROM AUTHOR]

Background Several studies have reported the prognostic value of natriuretic peptides, but their predictive value in patients with diabetes mellitus is unknown. The aim of the study was to test the hypothesis that measurement of brain natriuretic peptide (BNP) levels in ambulatory patients with congestive heart failure (CHF) and diabetes can predict the occurrence of cardiovascular events at 6-month follow-up. Methods We enrolled 145 consecutive patient with diabetes [age 72 ± 9 years, hypertension (21%), ischaemic heart disease (52%), atrial fibrillation (22%), preserved left ventricular function (29%)] seen in the outpatient heart failure clinic after an acute episode of cardiac failure. Results The median (25th/75th interquartile range) BNP concentrations at discharge were 186 (75–348) pg/ml. At 6-month clinical follow-up 10/145 (7%) subjects had died and 31/145 (21%) had been readmitted because of cardiac decompensation. BNP values of 200 and 500 pg/ml were found to have the best compromise between sensitivity (88 and 46%, respectively) and specificity (71 and 89%, respectively) for predicting events at 6 months. Multivariate Cox regression analysis identified only two parameters as predictors of events: serum creatinine [hazard ratio (HR) = 3.3; P = 0.02], and BNP plasma level BNP cut-off values (HR = 3.8; P = 0.03 for 201–499 pg/ml and HR = 7.7; P = 0.001 for ≥ 500 pg/ml). Conclusion These results suggest that BNP and serum creatinine are strong predictors of clinical events in patients with diabetes and CHF. In these patients, clinical outcome might be stratified by plasma BNP levels. [ABSTRACT FROM AUTHOR]

An abstract of the study "Feasibility, Safety and Ability of Cardiopulmonary Exercise Test in Elderly Patients with Chronic Heart Failure," by A. B. Scardovi and colleagues is presented.

An abstract of the study "Utility of BNP in detecting diastolic dysfunction in chronic heart failure patients," by A. B. Scardovi et al, is presented.

An abstract of the study "Rapid BNP test and doppler echocardiography provide a cost-effective screen for early diagnosis of heart failure," by N. Aspromonte and colleagues, is presented.

An abstract of the article "Role of the Combination of Multiple Clinical, Laboratory and Instrumental Parameters in Risk Assessment of Patients With Chronic Heart Failure," by A. B. Scardovi and colleagues is presented.

An abstract of the study "Prognostic Additional Value of Cardiopulmonary Exercise Test in Risk Assessment of Elderly Patients With Chronic Heart Failure," by R. De Maria and colleagues is presented.

An abstract of the study "The Combination of Neurohormonal, Ventilatory and Echocardiographic Evaluation Improves Risk Stratification in Patients With Chronic Heart Failure," by A. B. Scardovi et al. is presented.

An abstract of the study "Prognostic Value of Brain Natriuretic Peptide and an Enhanced Ventilatory Response During Cardiopulmonary Exercise Test in Patients With Heart Failure," by A. B. Scardovi and colleagues is presented.

An abstract of the study "Correlation Between BNP and Cardiopulmonary Exercise Test Parameters in Risk Stratification of Patients with Chronic Heart Failure," by C. Coletta and M. Romano, is presented.

An abstract of the study "Can BNP levels predict severe diastolic dysfunction in patients with chronic heart failure?," by A. B. Scardovi and colleagues, is presented.

An abstract of the article "Can BNP level be a marker of enhanced ventilatory response (EVR) during exercise test in patients with chronic heart failure and intermediate-level peak VO2?," by A. B. Scardovi et al., is presented.

An abstract of the article "Can BNP level be a marker of enhanced ventilatory response (EVR) during exercise test in patients with chronic heart failure and intermediate-level peak VO2?," by A. B. Scardovi et al., is presented.