Thiol regulation of vascular function and phenotype

血管会产生许多维持心血管系统健康的物质。构成血管壁的细胞(内皮细胞和血管平滑肌细胞)含有抗氧化酶和化学抗氧化剂，包括谷胱甘肽(GSH)，它们有助于确保正常的功能。细胞内的GSH水平很高，这种化学物质被认为对抗氧化能力和血管功能有重要贡献。然而，关于GSH在不同类型的血管中的分布，或者它帮助促进正常的血管功能的机制，人们还不是很清楚。目前还没有太多的科学研究专门控制血管中的GSH水平，以研究这种化学物质过少或过多的后果，或者它如何与血管中的其他分子相互作用。本研究旨在发现GSH在全身不同血管类型中的分布，并研究降低GSH水平对这些血管控制血管扩张和收缩以及流向组织的血液功能的影响。我们还将确定GSH水平、血管功能和血管基因和蛋白质表达之间的关系。我们将研究GSH水平受损的血管对其他应激源的反应。此外，我们还将研究急性和慢性运动对血管GSH水平的影响，以及运动对GSH水平低下的血管的血管功能和特征的影响。这些实验将通过使用一些实验模型来完成，包括完整的大鼠、分离的血管和大鼠的分离心脏。从基础科学的角度了解GSH在血管功能调节中的作用对于了解信号系统是重要的，这些信号系统在决定健康和功能障碍的血管的分子组成和功能特征方面具有重要意义，直接造福于细胞和血管生物学家。临床研究人员可能会将其转化为许多明显的应用，直接影响普通加拿大人的生活。

Blood vessels produce a number of substances that maintain the health of the cardiovascular system. The cells that make up the blood vessel wall (endothelial cells and vascular smooth muscle cells) contain antioxidant enzymes and chemical antioxidants, including glutathione (GSH), that help ensure proper functioning. Cellular GSH levels are high and this chemical is believed to make an important contribution to antioxidant capacity and vascular function. However, there is not much known about the distribution of GSH in different types of blood vessels, or about the mechanisms by which it helps promote proper vascular function. There have not been very many scientific studies that have specifically manipulated blood vessel GSH levels to study the consequences of too little or too much of this chemical, or how it interacts with other molecules in the blood vessels. The studies in this proposal aim to discover the distribution of GSH in different blood vessel types throughout the body, and to study the effects that lowering GSH levels has on the function of these vessels in controlling dilation and constriction of the vessels and the blood flow to tissues. We will also determine what the relationship is between GSH levels, vascular function, and gene and protein expression of the blood vessels. We will investigate how the blood vessels that have compromised levels of GSH respond to other stressors. In addition we will study the effects of acute and chronic exercise on blood vessel GSH levels, and will examine the effects of exercise on vascular function and characteristics in blood vessels with compromised GSH levels. These experiments will be accomplished by using a number of experimental models including intact rats, isolated blood vessels and isolated heart from rats. Understanding the role of GSH in regulation of blood vessel function is important from a basic science point of view to understand the signaling systems that are important in determining the molecular composition and the functional characteristics of blood vessels in health and in dysfunction benefiting cell and vascular biologists directly. Clinical researchers may translate it into many obvious applications that can directly impact the lives of average Canadians.