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

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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.