Exercise and shear rate patterns: targeting age related atherosclerosis

随着年龄的增长，血管壁变得更加坚硬，这对血管壁上的细胞(内皮细胞)所经历的摩擦力(剪切力)产生了负面影响。此外，这些细胞表现出与年龄相关的功能障碍，从而增加了atherosclerosis(http://circ.ahajournals.org/content/123/17/1900.full).的风险在利兹大学(Birch/Greenwood)，这个项目将研究如何操纵运动来产生不同大小和模式的动脉血管壁切应力。急性或慢性运动方案可包括传统的中等强度运动、高强度间歇运动、金字塔运动和总能量消耗/功的控制。在运动期间和运动干预后，将使用超声波和磁共振成像来评估冠状动脉、主动脉、臂动脉和股动脉的血流，以便可以模拟剪切、剪切方向和剪切振荡，从而在孵化器中的冠状动脉细胞上复制。该项目将包括在exercise(http://heartresearch.org.uk/spending-money/cardiac-mri，http://onlinelibrary.wiley.com/doi/10.1113/expphysiol.2011.062836/abstract)期间对多普勒超声和心脏磁共振成像进行培训，然后在心血管科学系保罗·埃文斯教授的实验室进行内皮细胞生物学和细胞信号传递过程方面的培训。谢菲尔德大学(http://www.ncbi.nlm.nih.gov/pubmed/25230814).This生物学将评估炎症和动脉粥样硬化的关键途径。特定运动方案对切变率曲线和随后的内皮细胞生物学的影响将在衰老和病理过程的不同时间点进行检测。因此，研究学生将接受与转化医学相关的跨学科技术培训，并利用这些技能来评估有针对性的运动是否可以缓解导致病理的衰老过程的那些方面。这可能是流行的间歇性运动实际上是有害的，一旦出现老化特征，而持续的剪切力为细胞提供最有效的刺激。事实上，现实生活中的剪切剖面可以通过想象来确定，这是解决这些问题的一种独特的新方法。

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.