Endothelial NADPH oxidase-2 promotes interstitial cardiac fibrosis and diastolic dysfunction through proinflammatory effects and endothelial-mesenchymal transition

OBJECTIVES: This study sought to investigate the effect of endothelial dysfunction on the development of cardiac hypertrophy and fibrosis. BACKGROUND: Endothelial dysfunction accompanies cardiac hypertrophy and fibrosis, but its contribution to these conditions is unclear. Increased nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2) activation causes endothelial dysfunction. METHODS: Transgenic mice with endothelial-specific NOX2 overexpression (TG mice) and wild-type littermates received long-term angiotensin II (AngII) infusion (1.1 mg/kg/day, 2 weeks) to induce hypertrophy and fibrosis. RESULTS: TG mice had systolic hypertension and hypertrophy similar to those seen in wild-type mice but developed greater cardiac fibrosis and evidence of isolated left ventricular diastolic dysfunction (p < 0.05). TG myocardium had more inflammatory cells and VCAM-1-positive vessels than did wild-type myocardium after AngII treatment (both p < 0.05). TG microvascular endothelial cells (ECs) treated with AngII recruited 2-fold more leukocytes than did wild-type ECs in an in vitro adhesion assay (p < 0.05). However, inflammatory cell NOX2 per se was not essential for the profibrotic effects of AngII. TG showed a higher level of endothelial-mesenchymal transition (EMT) than did wild-type mice after AngII infusion. In cultured ECs treated with AngII, NOX2 enhanced EMT as assessed by the relative expression of fibroblast versus endothelial-specific markers. CONCLUSIONS: AngII-induced endothelial NOX2 activation has profound profibrotic effects in the heart in vivo that lead to a diastolic dysfunction phenotype. Endothelial NOX2 enhances EMT and has proinflammatory effects. This may be an important mechanism underlying cardiac fibrosis and diastolic dysfunction during increased renin-angiotensin activation.

Rapid machine tool verification

This paper describes work carried out to develop methods of verifying that machine tools are capable of machining parts to within specification, immediately before carrying out critical material removal operations, and with negligible impact on process times. A review of machine tool calibration and verification technologies identified that current techniques were not suitable due to requirements for significant time and skilled human intervention. A 'solution toolkit' is presented consisting of a selection circular tests and artefact probing which are able to rapidly verify the kinematic errors and in some cases also dynamic errors for different types of machine tool, as well as supplementary methods for tool and spindle error detection. A novel artefact probing process is introduced which simplifies data processing so that the process can be readily automated using only the native machine tool controller. Laboratory testing and industrial case studies are described which demonstrate the effectiveness of this approach.

A simple remote sensing based information system for monitoring sites of conservation importance

Monitoring is essential for conservation of sites, but capacity to undertake it in the field is often limited. Data collected by remote sensing has been identified as a partial solution to this problem, and is becoming a feasible option, since increasing quantities of satellite data in particular are becoming available to conservationists. When suitably classified, satellite imagery can be used to delineate land cover types such as forest, and to identify any changes over time. However, the conservation community lacks (a) a simple tool appropriate to the needs for monitoring change in all types of land cover (e.g. not just forest), and (b) an easily accessible information system which allows for simple land cover change analysis and data sharing to reduce duplication of effort. To meet these needs, we developed a web-based information system which allows users to assess land cover dynamics in and around protected areas (or other sites of conservation importance) from multi-temporal medium resolution satellite imagery. The system is based around an open access toolbox that pre-processes and classifies Landsat-type imagery, and then allows users to interactively verify the classification. These data are then open for others to utilize through the online information system. We first explain imagery processing and data accessibility features, and then demonstrate the toolbox and the value of user verification using a case study on Nakuru National Park, Kenya. Monitoring and detection of disturbances can support implementation of effective protection, assist the work of park managers and conservation scientists, and thus contribute to conservation planning, priority assessment and potentially to meeting monitoring needs for Aichi target 11.