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Properties and function of TRPC proteins in vascular smooth muscle using transgenic mice

使用转基因小鼠研究血管平滑肌中 TRPC 蛋白的特性和功能

基本信息

批准号：
BB/J007226/1
负责人：
Anthony Albert
金额：
$ 46.84万
依托单位：
St George's, University of London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FJ007226%2F1
关键词：
Properties function TRPC proteins vascular

项目摘要

The aim of our research is to discover molecules that control the diameter of blood vessels. These molecules will be future drug targets for prevention and treatment of cardiovascular disease (CVD).A recent survey showed that CVD such as high blood pressure, heart attack, and stroke, cause 40% of all deaths in the UK. Also, CVD costs us over £29 billion a year in healthcare, and loss of productivity due to lost work days. With an aging population, these figures are likely to rapidly increase. In light of these facts, we need new drugs to prevent and treat VD. Not enough flow of blood causes cells to not receive enough nutrients (e.g. oxygen), and to build up more waste products (e.g. carbon dioxide), which leads to cells not working properly. CVD often leads to blood vessels contracting too much, which contributes to a reduction in blood flow. Therefore it is important to find out how blood vessels contract. We study muscle cells found in the walls of blood vessels, which important in making blood vessels contract.It is known that calcium is an important molecule in making these muscle cells to contract. Our research investigates proteins, called TRPC channels, which are involved in increasing the concentration of calcium inside cells. TRPC channel proteins are pores which are found in the membrane that surrounds cells. Molecules cause these pores to open and close, which allows calcium to move into cells.TRPC channels are important in controlling how blood vessel contract, and are believed to be involved in contributing to high blood pressure, which is a major risk factor for CVD. The present work will investigate members of the TRPC channel protein family, TRPC1 and TRPC5, in blood vessels from mice, which are an excellent model for understanding what happens in human blood vessels.Our research we greatly advance knowledge on how blood vessel contract. This will ultimately help in the development of new treatments for CVD. It will also help understand other diseases, which involve TRPC channels and changes in calcium levels inside cells.

我们研究的目的是发现控制血管直径的分子。这些分子将成为未来预防和治疗心血管疾病（CVD）的药物靶点。最近的一项调查显示，CVD如高血压、心脏病发作和中风，导致英国40%的死亡。此外，CVD每年在医疗保健方面花费超过290亿英镑，以及由于工作日损失而导致的生产力损失。随着人口老龄化，这些数字可能会迅速增加。鉴于这些事实，我们需要新的药物来预防和治疗VD。血液流量不足会导致细胞无法获得足够的营养（例如氧气），并产生更多的废物（例如二氧化碳），从而导致细胞无法正常工作。心血管疾病通常会导致血管收缩过多，从而导致血流量减少。因此，了解血管如何收缩是很重要的。我们研究的是在血管壁中发现的肌肉细胞，这些细胞在使血管收缩中起重要作用。众所周知，钙是使这些肌肉细胞收缩的重要分子。我们的研究调查的蛋白质，称为TRPC通道，这是参与增加细胞内的钙浓度。TRPC通道蛋白是在包围细胞的膜中发现的孔。TRPC通道在控制血管收缩方面非常重要，被认为与高血压有关，而高血压是心血管疾病的主要危险因素。目前的工作将调查TRPC通道蛋白家族的成员，TRPC 1和TRPC 5，在小鼠的血管中，这是一个很好的模型，以了解在人类血管中发生了什么。我们的研究将大大推进知识如何血管收缩。这将最终有助于开发新的CVD治疗方法。它还将有助于了解其他疾病，这些疾病涉及TRPC通道和细胞内钙水平的变化。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced nitric oxide production and vasorelaxation in rabbit mesenteric arteries.

DOI：
10.1016/j.vph.2017.08.005
发表时间：
2017-09
期刊：
Vascular pharmacology
影响因子：
4
作者：
Greenberg HZE;Carlton-Carew SRE;Khan DM;Zargaran AK;Jahan KS;Vanessa Ho WS;Albert AP
通讯作者：
Albert AP

Stimulation of calcium-sensing receptors induces endothelium-dependent vasorelaxations via nitric oxide production and activation of IKCa channels.

DOI：
10.1016/j.vph.2016.01.001
发表时间：
2016-05
期刊：
Vascular pharmacology
影响因子：
4
作者：
Greenberg HZ;Shi J;Jahan KS;Martinucci MC;Gilbert SJ;Vanessa Ho WS;Albert AP
通讯作者：
Albert AP

Obligatory role for PKCdelta in activation of store-operated TRPC1 channels in vascular smooth muscle cells

PKCdelta 在血管平滑肌细胞中存储操纵的 TRPC1 通道激活中的必然作用