Interactions between mts 1 and serotonin in vascular remodelling

mts 1 和血清素在血管重塑中的相互作用

• 批准号: BB/D007623/1
• 负责人: Margaret MacLean
• 金额: $ 29.65万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD007623%2F1
• 关键词: Interactions; between; mts; serotonin; vascular

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.

血管增厚（称为重塑）发生在许多与心血管系统相关的疾病中，并与高血压（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向身体其他部位供应血液的血管（全身动脉）。许多因素有助于动脉的重塑。最近的证据表明，体内一种叫做血清素的化学物质可以与另一种叫做mts 1的化学物质相互作用，导致肺动脉重塑。这已在分离的细胞中显示，但这是否发生在整个动物中需要研究。我们已经建立了旨在研究转基因小鼠的肺动脉和体动脉的技术，无论是在整个动物中，在非常小的动脉水平和细胞水平。将这些技术应用于那些人工增加了允许5-羟色胺进入细胞的孔（5-羟色胺转运蛋白）和mts 1表达的小鼠，将使我们能够研究这种潜在的重要的血管重塑机制。此外，缺氧（缺氧）是肺动脉重塑的重要介质，我们已经开发了将小鼠和细胞暴露于缺氧环境的技术。这将被应用于研究缺氧，血清素和mts 1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mts 1和5-羟色胺之间是否存在导致肺动脉重塑的重要相互作用。这将通过检查过表达mts 1的小鼠和过表达5-羟色胺转运蛋白的小鼠中的这些相互作用来完成。这些小鼠也将被杂交，以培育出同时过表达血清素转运体和mts 1的小鼠。进一步的实验将在来自这些“模型”的血管和来自这些血管的培养物中生长的细胞上进行。这将清楚地说明细胞内相互作用与全身功能的关系。这项工作有很多益处和应用，包括了解mts 1、血清素和缺氧如何影响血管功能，以及这种变化在疾病中是如何发生的，以及如何预防这种变化。它将为高血压等重塑性疾病提供新的治疗方法。

项目成果

Development of pulmonary arterial hypertension in mice over-expressing S100A4/Mts1 is specific to females.

• DOI: 10.1186/1465-9921-12-159
• 发表时间: 2011-12-20
• 期刊: Respiratory research
• 影响因子: 5.8
• 作者: Dempsie Y;Nilsen M;White K;Mair KM;Loughlin L;Ambartsumian N;Rabinovitch M;Maclean MR
• 通讯作者: Maclean MR