Pressure Load: The Main Factor for Altered Gene Expression in Right Ventricular Hypertrophy in Chronic Hypoxic Rats

BACKGROUND: The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading. METHODOLOGY/PRINCIPAL FINDINGS: To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB), sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein) were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase) were downregulated in the PTB and upregulated in the hypoxic experiment. CONCLUSION/SIGNIFICANCE: Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure

"I'm on autopilot, I just follow the route": exploring the habits, routines, and decision-making practices of everyday urban mobilities

Much urban and transport policy is based on a series of assumptions relating to predefined journeys informed by rational decision making. For example, the dominant focus of urban pedestrian policy is how the built environment is the primary influence on a person’s decision to walk, with these decisions being made at a specific time and place somehow outside the practice of walking. Little attention is given to the importance of the processual and experiential dimensions of walking itself. This paper considers the ways in which journeys into and through, the city unfold. Specific attention is drawn to how forms of habitual performance, such as practical knowledge and embodied habits and routines, assist in engaging with everyday urban movements. In the context of in-depth research conducted in London, the paper explores the habits and routines of urban pedestrian mobilities such as the daily commute and in so doing, highlights the complexity and ongoing reconfiguration of these journeys beyond analysis informed by ‘rational’ intention. In contrast to much transport research that conceives of habit as an external force that somehow obstructs more positive sustainable travel behaviour, discussion focuses on the significance of how everyday urban walking unfolds. It is argued that this form of engagement makes it possible to understand habit as situated and part and parcel of the sequentially organised and occasioned performance of journeys on foot. This, in turn, enables the transformative potential of habitual behaviour to be realised. Throughout the paper consideration is given to specific narratives of everyday urban mobilities; the significance of how such practices are actually ‘talked about’; and how these accounts matter in engaging with the experiential dimensions of urban movement