Exercise and shear rate patterns: targeting age related atherosclerosis

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The blood vessel wall becomes stiffer with the aging process and this negatively impacts the frictionalforces (shear) experienced by the cells lining the vessel wall (endothelial cells). In addition these cellsdisplay age related dysfunction that increases the risk of atherosclerosis(http://circ.ahajournals.org/content/123/17/1900.full). At the University of Leeds (Birch/Greenwood)this project will investigate how exercise can be manipulated to produce differing magnitudes andpatterns of shear stress along arterial vascular walls. Acute or chronic exercise regimes may includetraditional moderate intensity exercise, exercise performed as high intensity intervals, exerciseperformed in pyramids and manipulated for total energy expenditure/work. These regimes can bestratified to aging and/or patient populations.Blood flow in the coronary vessels, the aorta, the brachial and femoral arteries will be evaluatedduring exercise, and following an exercise intervention, using both ultrasound and magneticresonance imaging so that shear, direction of shear and oscillations in shear can be modelled andthus reproduced over coronary artery cells within an incubator. The project will include training inDoppler ultrasound and cardiac magnetic resonance imaging during exercise(http://heartresearch.org.uk/spending-money/cardiac-mri,http://onlinelibrary.wiley.com/doi/10.1113/expphysiol.2011.062836/abstract) and then in the biology ofendothelial cells and cell signalling processes in the laboratory of Prof. Paul Evans, DeptCardiovascular Sciences, University of Sheffield (http://www.ncbi.nlm.nih.gov/pubmed/25230814).This biology will assess the key pathways of inflammation and atherosclerosis.The impact of specific exercise regimes upon shear rate profiles and subsequent endothelial cellbiology will be examined at different points in the aging and pathological process. Thus the researchstudent will have training in interdisciplinary techniques pertinent to translational medicine and willutilise these skills to evaluate whether targeted exercise can alleviate those aspects of the agingprocess that lead to pathology. It may be that popular interval exercise is in fact detrimental toendothelial cells once aging characteristics are present and that constant shear offers the mosteffective stimulus to the cells. The fact that real life shear profiles can be determined via imagingoffers a distinct novel approach to these questions.