Exercise and shear rate patterns: targeting age related atherosclerosis

随着年龄的增长，血管壁变得越来越硬，这对血管壁细胞（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，这增加了动脉粥样硬化的风险（http：//circ.ahajournals.org/content/123/17/1900.full）。在利兹大学（伯奇/格林伍德），该项目将研究如何操纵运动，以产生不同大小和模式的剪切应力沿着动脉血管壁。急性或慢性运动方案可以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/功控制运动。这些方案可以根据年龄和/或患者人群进行分层。冠状动脉、主动脉、肱动脉和股动脉中的血流将在运动过程中进行评估，并在运动干预后进行评估，使用超声和磁共振成像，从而可以模拟剪切、剪切方向和剪切振荡，从而在培养箱中的冠状动脉细胞上重现。该项目将包括在运动中训练多普勒超声和心脏磁共振成像（http：//heartresearch.org.uk/spending-money/cardiac-mri，http：//onlinelibrary.wiley.com/doi/10.1113/expphysiol.2011.062836/abstract），然后在谢菲尔德大学心血管科学系Paul Evans教授实验室的内皮细胞和细胞信号传导过程生物学中（网址：//www.ncbi.nlm.nih.gov/pubmed/25230814)。这项生物学研究将评估炎症和动脉粥样硬化的关键途径。在衰老和衰老的不同阶段，将研究特定运动方案对剪切率曲线和随后的内皮细胞生物学的影响。病理过程。因此，研究生将接受与转化医学相关的跨学科技术培训，并将利用这些技能来评估是否有针对性的运动可以减轻导致病理学的衰老过程的那些方面。这可能是流行的间歇运动实际上是有害的内皮细胞一旦老化的特点是目前和恒定的剪切提供了最有效的刺激细胞。真实的生活剪切剖面可以通过成像来确定，这一事实为这些问题提供了一种独特的新方法。

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.