Interactions between mts 1 and serotonin in vascular remodelling

血管增厚（称为血管重构）发生在许多与心血管系统相关的疾病中，并与高血压有关。这可能发生在供应肺部的血管（肺动脉）、供应心脏和大脑的血管以及供应身体其他部位血液的血管（全身动脉）中。许多因素导致动脉的重塑。最近的证据表明，人体内一种名为血清素的化学物质可以与另一种名为mts1的化学物质相互作用，导致肺动脉重构。这已经在分离的细胞中得到证实，但这是否发生在整个动物身上还需要调查。我们已经建立了技术来研究转基因小鼠的肺动脉和全身动脉，在整个动物中，在非常小的动脉水平和细胞水平上。将这些技术应用于人工增加允许5 -羟色胺进入细胞的孔（5 -羟色胺转运体）和mts1表达的小鼠，将使我们能够研究这种潜在的血管重塑的重要机制。此外，缺氧是肺动脉重构的重要媒介，我们已经开发了将小鼠和细胞暴露于缺氧环境的技术。这将用于研究缺氧、血清素和mts1之间的相互作用。这项工作的主要目的是在整个动物中确定mts1和血清素之间是否存在导致肺动脉重塑的重要相互作用。这将通过在过表达mts1的小鼠和过表达血清素转运体的小鼠中检查这些相互作用来完成。这些小鼠也将被杂交培育出过度表达血清素转运体和mts1的小鼠。进一步的实验将在这些“模型”衍生的血管和从这些血管中培养出来的细胞上进行。这将使我们清楚地了解细胞内相互作用与全身功能的关系。这项工作有很多好处和应用，包括了解mts1、血清素和缺氧如何影响血管功能，这种变化如何在疾病中发生，以及如何预防这种变化。它将为高血压等疾病的重塑提供新的治疗方法。

Thickening of blood vessels (known as remodelling) occurs in many diseases associated with the cardiovascular system and is related to high blood pressure (hypertension). This can occur in the blood vessels that supply the lungs (pulmonary arteries), those that supply the heart and the brain as well as those that supply blood to the rest of the body (systemic arteries). Many factors contribute to the remodelling of arteries. Recent evidence suggests that a chemical in the body known as serotonin can interact with another chemical known as mts1 to cause pulmonary arterial remodelling. This has been shown in isolated cells but whether or not this occurs in the whole animal requires investigation. We have established techniques designed to investigate pulmonary and systemic arteries in transgenic mice, both in the whole animal, at the level of the very small arteries and at the cellular level. Application of these techniques to mice that have an artificial increase in the expression of the pore that allows serotonin to enter the cell (the serotonin transporter) and mts1 will enable us to investigate this potentially important mechanism for vascular remodelling. In addition, lack of oxygen (hypoxia) is an important mediator of pulmonary arterial remodelling and we have developed techniques for exposing mice and cells to a hypoxic environment. This will be applied to study the interaction between hypoxia, serotonin and mts1. The major aim of the work is to establish, in the whole animal, if there is an important interaction between mts1 and serotonin that causes a remodelling of the pulmonary arteries. This will be done by examining these interactions in mice over-expressing mts1 and mice over-expressing the serotonin transporter. These mice will also be cross-bred to develop mice that over-express both the serotonin transporter and mts1. Further experiments will be carried out on blood vessels derived from these 'models' and from cells grown up in culture from these blood vessels. This will give a clear picture of how intracellular interactions relate to whole body function. There are many benefits and applications of this work, including knowledge of how mts1, serotonin and hypoxia affect vascular function, how this changes in disease and how such changes could be prevented. It will suggest novel therapies for remodelling diseases such as hypertension.