Nerve growth factor (NGF) delivery to the brain of patients appears to be an emerging potential therapeutic approach to neurodegenerative disease, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracerebroventricular infusion and gene therapy. We previously showed that intranasal administration of NGF determined an amelioration of cholinergic deficit and a decrease in the number of phosphotaupositive neurons and of ␤-amyloid accumulation in AD11 mice, which express transgenic antibodies neutralizing NGF action and exhibit a progressive Alzheimer-like neurodegeneration. In this study, we report that the Alzheimer-like neurodegeneration in AD11 mice is linked to progressive behavioral deficits in visual recognition memory and spatial memory starting from 4 months of age. To establish whether intranasal administration of NGF, started after the appearance of the first memory deficits, could revert the cognitive deficits in AD11 mice, we assessed the performance of NGF-treated or control AD11 mice in the object recognition test and in a test of memory for place and context. Deficits exhibited by untreated AD11 mice could be rescued by the intranasal administration of NGF. Thus, this route of administration provides a promising way to deliver NGF to the brain in a therapeutic perspective.Alzheimer's disease ͉ behavior ͉ mouse model

Cardiovascular disease (CVD) accounts for the majority of death and hospitalization, health care expenditures and loss of productivity in developed country. CVD research, thus, plays a key role for improving patients' outcomes as well as for the sustainability of health systems. The increasing costs and complexity of modern medicine along with the fragmentation in healthcare organizations interfere with improving quality care and represent a missed opportunity for research. The advancement in diagnosis, therapy and prognostic evaluation of patients with CVD, indeed, is frustrated by limited data access to selected small patient populations, not standardized nor computable definition of disease and lack of approved relevant patient-centered outcomes. These critical issues results in a deep mismatch between randomized controlled trials and real-world setting, heterogeneity in treatment response and wide inter-individual variation in prognosis. Big data approach combines millions of people's electronic health records (EHR) from different resources and provides a new methodology expanding data collection in three direction: high volume, wide variety and extreme acquisition speed. Large population studies based on EHR holds much promise due to low costs, diminished study participant burden, and reduced selection bias, thus offering an alternative to traditional ascertainment through biomedical screening and tracing processes. By merging and harmonizing large data sets, the researchers aspire to build algorithms that allow targeted and personalized CVD treatments. In current paper, we provide a critical review of big health data for cardiovascular research, focusing on the opportunities of this largely free data analytics and the challenges in its realization.

The overall plaque burden and plaque phenotypes are associated with changes in the kinetics of miR-concentrations across the transcoronary passage. Transcoronary gradients of the anti-atherosclerotic miR-126-3p and miR-145-5p correlated with the extent of TCFAs, suggesting that instable plaques may affect the local uptake or degradation of these miRs.

Rationale: Endothelial progenitor cells (EPCs) are present in the systemic circulation and home to sites of ischemic injury where they promote neoangiogenesis. β 2 -Adrenergic receptor (β 2 AR) plays a critical role in vascular tone regulation and neoangiogenesis. Objective: We aimed to evaluate the role of β 2 AR on EPCs’ function. Methods and Results: We firstly performed in vitro analysis showing the expression of β 2 AR on EPCs. Stimulation of wild-type EPCs with β-agonist isoproterenol induced a significant increase of Flk-1 expression on EPCs as assessed by fluorescence-activated cell sorter. Moreover, β 2 AR stimulation induced a significant increase of cell proliferation, improved the EPCs migratory activity, and enhanced the EPCs’ ability to promote endothelial cell network formation in vitro. Then, we performed in vivo studies in animals model of hindlimb ischemia. Consistent with our in vitro results, in vivo EPCs’ treatment resulted in an improvement of impaired angiogenic phenotype in β 2 AR KO mice after induction of ischemia, whereas no significant amelioration was observed when β 2 AR knock out (KO) EPCs were injected. Indeed, wild-type–derived EPCs’ injection resulted in a significantly higher blood flow restoration in ischemic hindlimb and higher capillaries density at histological analysis as compared with not treated or β 2 AR KO EPC-treated mice. Conclusions: The present study provides the first evidence that EPCs express a functional β 2 AR. Moreover, β 2 AR stimulation results in EPCs proliferation, migration, and differentiation, enhancing their angiogenic ability, both in vitro and in vivo, leading to an improved response to ischemic injury in animal models of hindlimb ischemia.

ticular morphological features, which are differentially connected to the risk of plaque disruption and subsequent thrombus apposition, risk of vessel occlusion and acute coronary events. 2 Optical coherence tomography (OCT) is a light-based intravascular imaging modality that allows for high-resolution visualization of the coronary atherosclerotic plaques. 3 Currently, OCT provides the most detailed insights into plaque characteristics, allowing the measurement of lipid-pool extension and the thickness of the fibrous cap, as well as the identification of local plaque inflammation, all of which may represent key factors in A therosclerosis is a multifactorial disease that results from a complex interaction between genetic predisposition and well-recognized cardiovascular risk factors (CVRF), such as diabetes mellitus, arterial hypertension, hypercholesterolemia, smoking, obesity and age. The relationship between CVRF and the risk of experiencing a coronary event is widely acknowledged. 1 Nevertheless, the mechanisms underlying the role of individual risk factors in the development and progression of atherosclerotic plaques are currently not fully understood. Pathological and imaging studies have demonstrated that the morphological composition in large part reflects the fate of an atherosclerotic plaque. 2 It has been demonstrated that "stable" and "vulnerable" plaques show distinct and parEditorial p 1100 The association between cardiovascular risk factors (CVRF) and the risk of coronary events is widely acknowledged.Whether individual risk factors may be associated with distinct plaque characteristics is currently unclear. We investigated the relationship between CVRF and coronary plaque burden and phenotype.

BackgroundThe clinical impact of PlA2 polymorphism has been investigated in several diseases, but the definition of its specific role on thrombotic cardiovascular complications has been challenging. We aimed to explore the effect of PlA2 polymorphism on outcome in patients with atherosclerosis.MethodsWe studied 400 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention. A replication study was conducted in 74 hypertensive patients with cerebrovascular events while a group of 100 healthy subjects was included as control population. PlA genotype was determined by PCR-RFLP on genomic DNA from peripheral blood cells. Major adverse cardiac events (MACE), were considered as end points, and recorded at a mean follow up of 24 ± 4.3 months.ResultsThe frequencies of PlA2 polymorphism was similar between groups and genotype distribution was in Hardy-Weinberg equilibrium. In patients with CAD, the presence of PlA2 allele was associated with higher incidence of cardiac death (13.1% vs. 1.5%, p = 0.0001), myocardial infarction (10.7% vs. 2.6%, p = 0.004) and needs of new revascularization (34.8% vs. 17.7%, p = 0.010). Accordingly, the Kaplan-Meier analysis for event free survival in patients harboring the PlA2 allele showed worse long-term outcome for these patients (p = 0.015). Cox regression analysis identified the presence of PlA2 as an independent predictor of cardiac death (OR: 9.594, 95% CI: 2.6 to 35.3, p = 0.002) and overall MACE (OR: 1.829, 95% CI: 1.054 to 3.176, p = 0.032). In the replication study, the PlA2 polymorphism increased the risk of stroke (OR: 4.1, 95% CI: 1.63-12.4, p = 0.02) over TIA and was identified as an independent risk factor for stroke (B:-1.39; Wald: 7.15; p = 0.001).ConclusionsOur study demonstrates that in patients with severe atherosclerosis the presence of PlA2 allele is associated with thrombotic cardiovascular complications.

This meta-analysis demonstrates that, in selected coronary lesions, direct stenting improves outcome in patients undergoing percutaneous coronary intervention, primarily reducing myocardial infarction incidence.

Physical activity has a therapeutic role in cardiovascular disease (CVD), through its beneficial effects on endothelial function and cardiovascular system. Circulating endothelial progenitor cells (EPCs) are bone marrow (BM) derived cells that represent a novel therapeutic target in CVD patients, because of their ability to home to sites of ischemic injury and repair the damaged vessels. Several studies show that physical activity results in a significant increase in circulating EPCs, and, in particular, there are some evidence of the beneficial exercise-induced effects on EPCs activity in CVD settings, including coronary artery disease (CAD), heart failure (HF), and peripheral artery disease (PAD). The aim of this paper is to review the current evidence about the beneficial effects of physical exercise on endothelial function and EPCs levels and activity in both healthy subjects and patients with CVD.