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

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的药物靶点。最近的一项调查显示，高血压、心脏病发作和中风等心血管疾病导致的死亡占英国所有死亡人数的40%。此外，CVD每年在医疗保健方面的成本超过290亿GB，以及因工作日损失而造成的生产力损失。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。血液流动不足会导致细胞无法获得足够的营养(例如氧气)，并积累更多的废物(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，重要的是找出血管是如何收缩的。我们研究在血管壁中发现的肌肉细胞，它对血管收缩很重要。众所周知，钙是使这些肌肉细胞收缩的重要分子。我们的研究调查了被称为TRPC通道的蛋白质，它参与了增加细胞内钙浓度的过程。TRPC通道蛋白是存在于细胞周围膜上的小孔。分子导致这些毛孔的打开和关闭，从而允许钙进入细胞。TRPC通道在控制血管收缩方面非常重要，据信与高血压有关，高血压是心血管疾病的主要风险因素。这项工作将研究小鼠血管中TRPC通道蛋白家族的成员TRPC1和TRPC5，这是了解人类血管发生什么的一个很好的模型。我们的研究极大地促进了对血管收缩的了解。这最终将有助于开发治疗心血管疾病的新方法。它还将有助于理解其他疾病，这些疾病涉及TRPC通道和细胞内钙水平的变化。

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.