The influence of shear stress and sex hormones on vascular function and structure

剪切应力和性激素对血管功能和结构的影响

• 批准号: RGPIN-2019-04894
• 负责人: Pyke, Kyra
• 金额: $ 2.4万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=715182
• 关键词: influence; shear; stress; sex; hormones

Arteries are composed of a ring of connective tissue and muscle lined by a single layer of cells called the vascular endothelium. Constantly exposed to the frictional force of the flowing blood (shear stress) endothelial cells play a major role in determining arterial function and structure. The endothelium has the capacity to release substances that relax the muscle in the arterial wall, which widens (dilates) the artery and allows more flow. Endothelial cell function can be determined by applying specific stimuli (e.g. drugs or increasing shear stress) and then measuring the arterial dilation. A larger dilatory response is indicative of better endothelial function. The stiffness of arteries refers to the degree to which they can be distended by pressure. This capacity is influenced over the long term by structural changes in the composition of the vascular wall. In the short term, changes in blood pressure and in the contraction (tone) of the muscle in the arterial wall result in acute changes in arterial stiffness. In my research program we assess endothelial function in large and small vessels in the upper and lower limbs and assess arterial stiffness in the central arteries (near the heart) and peripheral arteries (in the limbs). This will gives us a whole body, multifaceted understanding of vascular function and structure in healthy men and women. In the proposed research we will use innovative techniques to address key gaps in understanding regarding how arteries are influenced by sex differences and experiences encountered in daily life. The proposal includes four specific short term objectives: 1) To characterize the impact of cyclic fluctuation in the primary female sex hormone estrogen over multiple menstrual/oral contraceptive pill cycles; establishing whether there are consistent trait-like' individual differences. 2) To identify and explain the interaction between estrogen level and vascular responses to acute challenges (e.g. an acute, stressful event). 3) To characterize regional differences in the impact exercise training characteristics (duration and intensity). 4) To establish the impact of artery size on the ability of endothelial cells to respond to increases shear stress; this is critical to comparing responses in men and women. The proposed research will advance our understanding of vascular physiology in the integrated human system. Study design and execution will be lead by undergraduate and graduate students, supporting a rich training environment which develops skills that foster the capacity for innovation and critical thinking. This is important to support the development of research leaders and the long term success of research in Canada, which benefits all Canadians.

动脉是由一圈结缔组织和肌肉组成的，周围是一层叫做血管内皮的细胞。内皮细胞不断暴露于血流的摩擦力（剪切应力）中，在决定动脉功能和结构中起着重要作用。内皮具有释放物质的能力，这些物质可以放松动脉壁的肌肉，使动脉变宽（扩张），允许更多的血流。内皮细胞的功能可以通过施加特定的刺激（如药物或增加剪应力），然后测量动脉扩张来确定。较大的扩张反应表明内皮功能较好。动脉的硬度是指动脉可以被扩张的程度