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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=685078
• 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.

动脉由一圈结缔组织和肌肉组成，内衬一层称为血管内皮的细胞。不断受到流动血液的摩擦力（剪切应力）的内皮细胞在决定动脉功能和结构方面发挥着重要作用。内皮有能力释放放松动脉壁肌肉的物质，从​​而加宽（扩张）动脉并允许更多流量。内皮细胞功能可以通过施加特定刺激（例如药物或增加剪切应力）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。动脉的僵硬度是指动脉在压力作用下可扩张的程度。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度的急剧变化。在我的研究项目中，我们评估上肢和下肢大血管和小血管的内皮功能，并评估中央动脉（靠近心脏）和外周动脉（四肢）的动脉僵硬度。 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身、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理解动脉如何受到性别差异和日常生活经历影响的关键差距。 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/口服避孕药周期内周期性波动的影响；确定是否存在一致的“特质状”个体差异。 2) 识别并解释雌激素水平与血管对急性挑战（例如急性应激事件）的反应之间的相互作用。 3) 描述冲击运动训练特征（持续时间和强度）的区域差异。 4) 确定动脉尺寸对内皮细胞响应剪切应力增加的能力的影响；这对于比较男性和女性的反应至关重要。 ******拟议的研究将增进我们对人体综合系统中血管生理学的理解。 研究设计和执行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。