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

动脉是由结缔组织和肌肉组成的环，内有一层称为血管内皮细胞的单层细胞。血管内皮细胞不断暴露在血液流动的摩擦力(剪切力)下，在决定动脉功能和结构方面起着重要作用。血管内皮细胞有能力释放松弛动脉壁肌肉的物质，从而使动脉变宽(扩张)，并允许更多的血流。内皮细胞功能可以通过施加特定刺激(如药物或增加切应力)，然后测量动脉扩张来确定。扩张性反应越大，血管内皮功能越好。动脉的僵硬是指动脉在压力作用下可以扩张的程度。从长远来看，这种能力受到血管壁成分的结构变化的影响。在短期内，血压和动脉壁肌肉收缩(张力)的变化会导致动脉僵硬的急剧变化。在我的研究计划中，我们评估了上肢和下肢大小血管的内皮功能，并评估了中央动脉(心脏附近)和外周动脉(四肢)的动脉硬度。这将使我们对健康男性和女性的血管功能和结构有一个全面、多方面的了解。在拟议的研究中，我们将使用创新技术来解决在理解动脉如何受到性别差异和日常生活中遇到的经验影响方面的关键差距。该提案包括四个具体的短期目标：1)描述主要女性性激素雌激素在多个月经/口服避孕药周期中的周期性波动的影响；确定是否存在一致的“类似特征”的个体差异。2)确定和解释雌激素水平和血管对急性挑战(例如，急性、应激事件)的反应之间的相互作用。3)探讨冲击性运动训练特征(持续时间和强度)的地区差异。4)确定动脉大小对内皮细胞对增加的剪切力的反应能力的影响；这对于比较男性和女性的反应至关重要。建议的研究将促进我们对完整人体系统中血管生理学的理解。研究设计和实施将由本科生和研究生领导，支持丰富的培训环境，培养培养创新能力和批判性思维能力的技能。这对于支持研究领导者的发展和加拿大研究的长期成功非常重要，这将使所有加拿大人受益。

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.